tbuckley/cabot-search huggingface dataset:
Pelvic reconstruction for malignant bone tumors using recycled frozen autograft.
Authors: Yu Aoki, Norio Yamamoto, Toshiharu Shirai, Hideji Nishida, Katsuhiro Hayashi, Yoshikazu Tanzawa, Hiroaki Kimura, Akihiko Takeuchi, Kentaro Igarashi, Hiroyuki Inatani, Shingo Shimozaki, Takashi Kato, Takashi Higuchi, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

e21505 Background: Pelvic reconstructive surgery after the resection of a pelvic tumor is most challenging. Since 1999, we have developed and clinically applied a novel method of biological reconstruction using a tumor-bearing autograft treated with liquid nitrogen. The purpose of this study was to assess the functional outcome and complications of tumor-bearing autografts treated with liquid nitrogen for pelvic reconstruction. Methods: Eleven patients (seven male and four female) were enrolled in this study, with a mean age of 49 years (range: 24–72 years). Seven patients had primary malignant tumors (three with osteosarcoma, two with chondrosarcoma, one with Ewing’s sarcoma, and one with low-grade fibromyxoid sarcoma), and four patients had isolated metastases (one with breast cancer, one with vaginal cancer, and two with renal cell carcinoma). We excluded patients who underwent palliative surgeries. In 10 patients, pelvic reconstruction using a frozen autograft was performed, and in one patient, a frozen autograft-prosthesis composite was used. The surgical techniques were composed of an en bloc excision of the tumor, removal of the soft tissue, curettage of the tumor and drilling, freezing in liquid nitrogen for 20 min, thawing at room temperature for 15 min, thawing in distilled water for 15 min, and internal fixation with either plate or composite use of the prosthetic replacement. Time of bone union, incidence of complications, and limb function (ISOLS score) were evaluated. Results: The mean follow-up period was 47 months (range: 7–115 months). Bone union of the frozen autograft to the host bone was observed in all patients, with a mean duration of 9 months (range: 6–13 months). Complications observed were deep infection (n = 1), osteoarthritis (n = 2), and local recurrences arising in peripheral soft tissues (n= 1). Total hip arthroplasty was performed as a salvage surgery for osteoarthritis. Limb function was rated as excellent in five patients, good in five, and poor in one. Conclusions: Although some complications still remained, frozen autografts treated with liquid nitrogen achieved favorable limb function, and this would be a useful option for biological pelvic reconstruction.
Thyroid and glucocorticoid status of patients having single and multiple primary colon cancer.
Authors: Margarita Kozlova, Oleg Ivanovich Kit, Elena Frantsiyants, Elena Alekseevna Nikipelova, Michail Averkin, Yulia Pogorelova
Journal: Journal of Clinical Oncology (2014)

e22237 Background: For patients having colon cancer (CC), the status of the thyroid body and suprarenal cortex hormones is important, as they are the principal cell, tissue and organ bioregulators. Methods: The content of T3, T4 (total and free forms), TSH and cortisol in blood of 84 patients of both sexes (aged 64.8 years on average) having single (SCC, n=30) and multiple primary (MPCC, n=54), stages II-III of the disease was determined before the beginning of treatment using the radioimmunoassay technique. Results: In all variants of the CC, valid reduction of the level of T4free (1.5 times lower for SCC, on average 1.3 times – for both variants of MPCC) in the blood was marked accompanied by the lower T4total in all patients having SCC (2.3 times) and in 65% of MPCC patients (1.5 times on average) Thyroxin deficiency discovered could be conditioned by the decreased T4-producing function of the thyroid body and/or by the change of blood transport globulins content and binding ability. In all variants of the CC, the level of T3total, the main part of which has non-thyroid origin and gets into the blood as a result of peripheral monodeiodization of T4, was also significantly reduced in 50% of patients (1.8-1.9 times lower), with the content of T3freebelow the norm in most patients (62%) having the metachronous CC and in 33% of patients having the SCC. By contrast, secretion of TSH remained at the control level in patients having both variants of MPCC yet it went down 2 times in 67% of SCC cases. Unlike the status of thyroid hormones, hypercortisolemia was discovered in all patients having the SCC and most MPCC ones, with the hormones level increased 2.1-2.7 times. Conclusions: Given the influence of thyroid hormones and cortisol on the development of defense reactions and the activity of the immune system, any disorders of their status have to be borne in mind while treating the CC patients.
Role of Notch-1 in epithelial-to-mesenchymal transition-induced erlotinib resistance of non-small cell lung cancer (NSCLC) cells.
Authors: Aamir Ahmad, Kevin Ginnebaugh, Fazlul H. Sarkar, Shirish M. Gadgeel
Journal: Journal of Clinical Oncology (2014)

e22136 Background: Primary and secondary resistance in Non-Small Cell Lung Cancer (NSCLC) to Epidermal Growth Factor Receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib is a major limitation of these drugs. Epithelial-to-Mesenchymal transition (EMT) has been suggested to play an important role in erlotinib resistance including in NSCLCs with EGFR mutations. Since Notch signaling has been mechanistically linked to EMT, we evaluated the role of Notch-1 in erlotinib resistance of NSCLC cells. Methods: Paired NSCLC cell lines, erlotinib sensitive HCC827 (exon 19 del EGFR mutation) and its erlotinib resistant derivative ER3, were used as the model system. Notch-1 was inhibited by the use of specific siRNA and the role of Notch-1-targeting microRNA, miR-34a, was evaluated by the use of specific pre- and anti-miRNA preparations. Results: Erlotinib resistant ER3 cells exhibited enrichment of mesenchymal markers and also over-expression of Notch-1, compared to HCC827 cells. Silencing of Notch-1 sensitized ER3 cells to erlotinib. This was accompanied by reversal of EMT as evidenced by increased expression of epithelial marker E-cadherin and reduced expression of mesenchymal markers Vimentin and ZEB1/2. Furthermore, the expression of miR-34a was found to be reduced in ER3 cells. Ectopic expression of miR-34a reduced the levels of Notch-1, resulting in attenuation of Notch-1-mediated effects on EMT and drug resistance. Conclusions: We present pre-clinical evidence in support of a mechanistic role of Notch-1 in EMT and the resulting erlotinib resistance of NSCLC cells. Further translational studies will be conducted to target Notch-1 for the reversal of EMT phenotype and attenuate erlotinib resistance in NSCLC.
Validity of the Swedish version of the systemic sclerosis quality of life questionnaire (SSCQoL): A novel measure of quality of life for patients with systemic sclerosis
Authors: Gunnel Sandqvist, Roger Hesselstrand
Journal: Annals of the Rheumatic Diseases (2019)

Systemic sclerosis (SSc) is an autoimmune disease characterised by microvascular injury and excessive fibrosis of the skin and internal organs,1 which influences activities of daily life2 and quality of life (QoL).3 The Medical Outcome Study Short Form-36, the EuroQol-5 Domain (EQ-5D) and the Patient-Reported Outcomes Measurement Information System 29-item are generic health-related QoL instruments, valid to be used in SSc.4 However, disease-specific tools could be more sensitive to capture disease-related factors influencing QoL. The Systemic Sclerosis Quality of Life Questionnaire (SScQoL), developed by Reay5 using a needs-based QoL model, is an outcome for assessing disease impact on health and well-being. The SScQoL consists of 29 items, covering the themes: function, emotion, sleep, social and pain. Each item with ‘yes’‘no’ response options are scored 1 and 0, respectively. The SScQoL has been sufficiently translated …
Head and neck squamous cell carcinoma (HNSCC), diabetes mellitus (DM), and metformin.
Authors: Abdulrahman Ali Alshehri, Roby Antony Thomas, Sijin Wen, Manish Monga
Journal: Journal of Clinical Oncology (2014)

e17040 Background: Metformin has been shown to decrease cancer incidence, recurrence and improve overall survival among DM patients with various malignancies. Evidence indicates that metformin may suppresse growth and viability of HNSCC via different mechanism of action. In this study we investigate the potential clinical benefit of metformin in HNSCC patients. Methods: Retrospective analysis of patients with diagnosis of squamous cell carcinoma arising from oral cavity, oropharynx, hypopharynx and larynx from 2004 to 2012 at our institution was performed. DM patients and Metformin users were identified. Clinical data such as Age, Sex, smoking, TNM stage and overall survival (OS) were analyzed for all patients. Statistical analysis was performed with S-PLUS Version 7.0. Results: A total of 743 patients with HNSCC origin were identified. Among those patients, there were 485 patients with non-laryngeal carcinoma and 258 patients with laryngeal carcinoma. 166 (22.3%) of the cohort had DM. Of those DM patients, 63 (37.9%) were on metformin therapy. There were no significant clinical differences between Diabetic patients including patients who were on metformin and non-diabetic patients in terms of sex, age, TNM stage at diagnosis, and smoking history. The median OS for all patients with SCC of head and neck origin who are diabetic was 3.3 years versus 5.3 years for non diabetic patients (p<0.005). Median overall survival for diabetic patients with laryngeal SCC was 3.5 years versus 4.9 years for non diabetic patients (p=0.128). Median OS for diabetic patients with non-laryngeal SCC was 2.5 years versus 5.7 years for non diabetic patients (p<0.019). Laryngeal SCC patients on metformin had a median OS of 3.53 years versus 3.39 years for non-users (p=0.942). For non-laryngeal SCC patients on metformin median OS was 3.1 years versus 2.5 years for non-users (p=0.691). Conclusions: Patients with HNSCC and DM had worse median OS as compared to patients without DM. Metformin use showed a 6 month improvement in survival in non-laryngeal HNSCC which was not statistically significant due to sample size. Clinical studies specifically designed to evaluate the efficacy of metformin as an anticancer agent in oral and oropharyngeal SCC are warranted.
Acute Myeloid Leukemia Expands Osteoprogenitor Rich Niche in the Bone Marrow but Resorbs Mature Bone Causing Osteopenia/Osteoporosis in Animal Models
Authors: Bin Yuan, Stanley Ly, Khoa Nguyen, Vivien Tran, Kiersten Maldonado, Charles Kinglsey, Jared K Burks, Xin Zhou, Benoit deCrombrugghe, Michael Andreeff, Venkata Lokesh Battula
Journal: Blood (2018)
Preoperative hyperthermia combined with chemoradiotherapy in locally advanced rectal cancer: Analysis in 67 patients.
Authors: Yuan Zhu, Jialin Luo, Luying Liu, Dechuan Li
Journal: Journal of Clinical Oncology (2014)

e14630 Background: Recent studies suggest that preoperative chemoradiotherapy in locally advanced rectal cancer can induce downstaging, but after resection the incidence of local recurrences remains high. Hyperthermia (HT) may add tumoricidal effects and improve the efficacy of chemoradiotherapy in a trimodal approach. This study was performed to determine the feasibility and efficacy in terms of response rate, resectability, and morbidity in patients with locally advanced rectal cancer who received preoperative regional hyperthermia combined with chemoradiotherapy (HCRT) . Methods: Sixty-seven patients with histologically proven primary unresectable rectal cancer (T3 or T4 or N+ lesions, as determined by endorectal ultrasound or Magnetic Resonance) entered the trial. Capecitabine was given at 800mg/m(2) orally twice daily Monday through Friday for week one, week two, week four, and week five concurrently with radiotherapy (RT). Oxaliplatin was given intravenously at 50mg/m(2) once weekly for week 1, week 2, week 4 and week 5, starting the first day of radiotherapy (50 Gy with 1.8Gy fractions for 5.5 weeks). Regional hyperthermia using the Endogenetic field tumor hyperthermia system (NRL-002, made in china) was given twice a week one hour before radiotherapy. Surgery followed four to six weeks after completion of HCRT. Results: Preoperative treatment was generally well tolerated, with 9% of patients developing grade III diarrhea. No grade IV complications were observed. 64 of 67 patients was operated, and 62 resection specimens had negative margins (R0). Three patients refused surgery. In 14 patients (22%), the histopathologic report confirmed no evidence of residual tumor (pCR). A partial remission (PR) was observed in 30 patients (47%). The median follow-up time was 56 months. The survival rate and local recurrence rate will be present at the conference time. Conclusions: Preoperative concurrent radiotherapy with capecitabine, oxaliplatin, and regional hyperthermia is feasible and effective for patients with primary unresectable rectal cancer. The good response rate observed warrants its use in further clinical trials.
Safety and Activity of the Investigational Bruton Tyrosine Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Mantle Cell Lymphoma from a Phase 2 Trial
Authors: Yuqin Song, Keshu Zhou, Dehui Zou, Jianfeng Zhou, Jianda Hu, Haiyan Yang, Huilai Zhang, Jie Ji, Wei Xu, Jie Jin, Fangfang Lv, Ru Feng, Sujun Gao, Daobin Zhou, Haiyi Guo, Aihua Wang, James Hilger, Jane Huang, William Novotny, Muhtar Osman, Jun Zhu
Journal: Blood (2018)
Treatment of patients with castration-resistant prostate cancer and bone metastases with radium-223: A single institution experience.
Authors: Srinivas S. Devarakonda, Justin Skweres, Binu Sivaraman Nair, Manish Dhawan, Amol Takalkar
Journal: Journal of Clinical Oncology (2014)

e16103 Background: Radium-223 dichloride (Ra-223), which selectively targets osteoblastic metastases with alpha particles, has been approved for treatment of castration-resistant prostate cancer (CRPC) and bone metastases. Radiographic assessment of osseous lesions in patients undergoing Ra-223 therapy was not performed during clinical trials. We report the data on patients being treated at our facility with Ra-223. Methods: An IRB approved retrospective chart review of CRPC patients with bone metastases treated with Ra-223 at our institution was performed. Absolute neutrophil count (ANC), hemoglobin (Hb), platelet count, serum alkaline phosphatase (AP) and serum prostate specific antigen (PSA) were assessed with each treatment. The skeletal lesions were evaluated with F-18 sodium fluoride (NaF) bone PET/CT scans performed at baseline, after 2 cycles and upon completion of treatment utilizing the maximum intensity of NaF uptake and maximum CT density in 5 discrete index bone lesions. Results: A total of 12 patients were treated between June 2013 and January 2014. Of the 6 monthly planned treatments, as of this writing, 2 patients have completed all the 6 treatments and 10 patients have received at least 2 treatments. Of the 12 patients, 5 had decline in AP, 2 had decline in PSA, 6 had reduction in SUVmax of the index lesions and 3 patients had increase in the HUmax of the index lesions after 2 treatments. Visual/subjective evaluation of the F-18 NaF bone PET/CT scans revealed progression in 5 patients and stable disease or improvement in the rest. All the patients reported improvement in their bone pain. Most common non-hematological adverse events (AE) included mild diarrhea and nausea, with no serious (i.e. requiring hospitalization) hematological AE so far. Treatment was discontinued in 4 patients after 3 to 4 cycles due to obvious disease progression. Conclusions: F-18 NaF bone PET/CT imaging may be a potentially valuable imaging tool to assess effect of Ra-223 on osseous metastases. More data and studies are needed to determine optimal timing and assessment parameters for optimal use of this imaging modality in CRPC and Ra-223 therapy.
A nonrandomized phase II trial of sorafenib (S) and everolimus (E) in unresectable metastatic osteosarcoma (OST) patients (pts) relapsed after standard chemotherapy.
Authors: Giovanni Grignani, Emanuela Palmerini, Virginia Ferraresi, Sebastian Dorin Asaftei, Lorenzo D'Ambrosio, Ymera Pignochino, Annamaria Nuzzo, Marco Gambarotti, Emanuela Marchesi, Roberto Biagini, Angela Tamburini, Rossella Bertulli, Paolo G Casali, Franca Fagioli, Piero Picci, Stefano Ferrari, Massimo Aglietta
Journal: Journal of Clinical Oncology (2014)

10533^ Background: After standard therapy OST relapse is an ominous event almost uniformly fatal in non resectable cases. Our group explored the activity of the multikinase inhibitor S demonstrating a short-lasting tumor growth arrest and 8% objective responses (OR). We hypothesized that other pathways might be responsible for S failure and we showed mTOR as a reasonable co-target to hit by means of E. Methods: Pts>17 years with relapsed unresectable OST, progressing after standard treatment, were eligible to receive S 400 mg b.i.d + E 5 mg once daily until progression (PD) or unacceptable toxicity. We designed a Simon two-stage study with progression-free survival rate at 6 months (PFS@6m) as the primary endpoint. With α=5%, β=10%, 37 pts were needed to test if PFS@6m was ≤25%=P0 (9 pts) or ≥50%=P1 (19 pts). Secondary endpoints were PFS, overall survival (OS), RECIST 1.1 OR, safety and their correlations with molecular markers of targeted pathways. We estimated PFS and OS by Kaplan-Meier method with their 95% confidence intervals (95% CI). All tests were two sided. Results: We enrolled 38 pts (15 females) from June 2011 to June 2013. PFS@6m was 45% (95%CI 28-61%, 17 pts). Median PFS and OS were 5 (95%CI 2-7) and 11 (95%CI 9-14) months, respectively. We observed 2 (5%) partial responses (PR), 2 minor responses (5%), 20 (53%) stable diseases (SD) for an OR of 10%. PR/SD lasted ≥ 6 months in 8 (21%) pts (6, 6, 7, 8, 8, 8, 10, 11). 1 pt interrupted the study because of lung metastasectomy after 10 months of disease control. Treatment was feasible but demanded both dose reductions and short interruptions for both drugs in 25 (66%) pts due to toxicity Treatment was permanently discontinued in 2 (5%) pts due to toxicity. Results of the correlation of ERK1 and pS6 expression with primary and secondary endpoints will be presented at the meeting. Conclusions: S + E showed activity in terms of PFS@6m as second- or further-line treatment in advanced unresectable OST with some long-lasting responses. Toxicity was manageable but required short interruptions, dose reductions and few permanent discontinuations. Despite some hints of activity, S + E failed to reach the prespecified target of PFS@6m. Clinical trial information: NCT01804374.
Granulocyte Transfusions for Neutropenic Patients with Perirectal and Perineal Infections
Authors: Darwin Roman, Hagop M. Kantarjian, Jorge E. Cortes, Gautam Borthakur, Guillermo Garcia-Manero, Marina Y. Konopleva, Courtney D. DiNardo, Naval G. Daver, Naveen Pemmaraju, Tapan M. Kadia, Steven M. Kornblau, Prithviraj Bose, Michael Andreeff, Emil J. Freireich, Farhad Ravandi, Fleur M. Aung
Journal: Blood (2018)
Biopsychosocial predictors of pain among women recovering from surgery for gynecologic cancer.
Authors: Kelsey R. Honerlaw, Stephen L. Rose, Christopher L. Coe, Meredith E. Rumble, Manish S. Patankar, David M. Kushner, Erin S. Costanzo
Journal: Journal of Clinical Oncology (2014)

9565 Background: Pain is a common and sometimes debilitating symptom for women recovering from surgery for gynecologic cancer, but little is known about psychological and biological risk factors that account for individual differences in pain. We investigated the extent to which psychological distress and inflammation were associated with pain post-surgery. Methods: Women (N=90) who underwent surgery for ovarian or endometrial cancer participated in this prospective, longitudinal study. They completed well-validated self-report measures of pain (intensity and interference with daily activities) and distress (depression and anxiety) at 1 week, 1 month, and 4 months post-surgery. Inflammatory cytokines were measured in peripheral blood at the same time points using an electrochemiluminescence platform. Mixed-effects and subject-level fixed-effects linear regression models were used to examine the extent to which distress measures and cytokines predicted pain intensity and interference. Results: Pain intensity and interference improved greatly over the four months post-surgery (p values<0.001).Participants who reported greater depression and anxiety experienced greater pain intensity (z=8.00, p<0.001; z=3.32, p=0.001). The same pattern was seen for pain interference. Those with higher IL-6 and IL-10 also experienced greater pain intensity (z=2.44, p=0.015; z=2.03, p=0.042), but not interference. All models controlled for time since surgery, surgical method (laparoscopy or laparotomy), disease stage, age, and BMI. Within-subjects analyses revealed that among individual patients, changes in distress and cytokine levels across the assessments were associated with corresponding changes in pain, with patients reporting greater pain intensity when depression (t=4.92, p<0.001), IL-6 (t=2.72, p=0.008), and IL-10 (t=2.40, p=0.019) were most elevated. Pain interference was greatest when depression (t=6.61, p<0.001) and anxiety (t= 2.58, p=0.011) were highest. Conclusions: Results suggest that depression, anxiety, and inflammation may exacerbate pain following surgery for gynecologic cancer. These risk factors can be targeted to improve post-surgical recovery and enhance quality of life.
Promoting intestinal lymphatic transport targets a liver-X receptor (LXR) agonist (WAY-252,623) to lymphocytes and enhances immunomodulation
Authors: Enyuan Cao, Anna Lindgren, Sofia Martinsson, Luojuan Hu, Lennart Lindfors, Kalle Sigfridsson, Urban Skantze, Erik Michaëlsson, Natalie L. Trevaskis, Christopher J.H. Porter
Journal: Journal of Controlled Release (2019)