tbuckley/cabot-search huggingface dataset:
Weekly chemotherapy with platinum as radio-sensitizer during concomitant chemoradiotherapy for squamous cell head and neck cancer
Authors: A. Caramalis, S. Nissel-Horowitz, U. Iqbal, R. Roy, N. Radhakrishnan, A. Thomas, J. Pollack, Y. Lebowicz, B. Mehrotra
Journal: Journal of Clinical Oncology (2007)

16541 Background: CRT protocols for locally advanced HNC commonly utilize single agent cisplatinum as the radiation- sensitizing chemotherpy. This is typically administered in q 3 weekly doses of 100 mg/sq m concomitantly with XRT. However, many pts are not candidates for this dose and schedule of cisplatinum delivery due to co-morbidities. Limited data are available regarding the efficacy of alternate dosing of platinum analogues.We therefore analysed our experience with alternate dosing of cisplatin or carboplatin administered concomitantly with XRT. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry and pharmacy data were reviewed to identify eligible pts. between 2004–2006 who were treated with alternate dosing of platinum with XRT. Pt characteristics recorded included: age, gender, stage, site of disease, type of chemotherpeutic agent used carboplatin or cisplatinum, number of doses administered, local disease free survival and overall survival. Results: Eleven pts were identified. Median age: 64 years (44–75); Gender: M:F::8:3; Sites: Oral cavity: n=2; Pharynx: n=11; Stage III: n=3; Stage IVa &amp;b: n=8. Cisplatin weekly (doses 30–40mg/sqm): n=8; Carboplatin weekly AUC=2: n=3; Cisplatin weekly, changed to carboplatin: n=1. Nine of 11 pts achieved a local CR (82%); one pt has achieved a near CR and one pt achieved a PR and required salvage laryngectomy. At a median follow up of 14 mos (range: 4–34), all pts remain alive. In addition to the pt that achieved a PR after initial treatment, one other pt has required surgical salvage at 23 mos post CRT. No treatment related mortality occurred in this series. Conclusions: Weekly administration of cisplatin and carboplatin appears to be a feasible alternative to standard dose and schedule of cisplatin with acceptable efficacy. Future studies should compare targetted therapies such as cetuximab with or in combination with weekly platinum regimens during CRT for pts not eligible for standard dose cisplatinum. No significant financial relationships to disclose.
Should early cancers of the oral tongue be kept under surveillance after wide excision alone? A prospective study
Authors: T. Gupta, J. Agarwal, A. D’Cruz, S. Ghosh-Laskar, R. Malde, M. Gupta, S. Shrivastava, K. Dinshaw
Journal: Journal of Clinical Oncology (2006)

5541 Background: The treatment of the clinically N0 neck in early stage oral tongue cancer remains controversial. Several clinico-pathologic criteria that can reliably identify an increased risk of occult metastases in the neck have been proposed. Our aim was to assess the impact of elective neck dissection (END) on outcome and correlate it with clinico-pathologic criteria for patient selection for surveillance. Methods: Patients with early stage cancer of the oral tongue (T1–2, N0) after undergoing wide excision with or without END were prospectively kept under observation. Patients having adverse histological features necessitating adjuvant radiotherapy were excluded. All patients gave informed consent and were closely followed. Relapsers were offered appropriate salvage therapy. The primary end-point for our prospective phase II study was the impact of END on relapse-free survival (RFS) with an estimated sample size of 50 patients. Overall survival (OS) was a secondary endpoint. Results: Fifty three eligible patients were consecutively accrued on the trial after surgery. Forty eight patients underwent per oral wide excision, with only 5 requiring a neck approach. Twenty two patients underwent upfront END. Twenty four patients relapsed (23 of which had some loco-regional component). The risk of neck recurrence in patients whose necks were not dissected electively was significantly higher than in patients treated with END (55% vs 9% respectively, p = 0.0016). The 3-year RFS (69.1% vs 40.9%, p = 0.008) and OS (87.2% vs 42.6%, p = 0.0228) was significantly better for patients treated with END. Conclusions: Regional recurrences are the most important cause of failure after wide excision alone. END which achieves excellent disease control in the neck and significantly improves RFS and OS should be considered routine for early stage oral tongue cancer. No significant financial relationships to disclose.
PIM: An Integral Component of FLT3 Signaling and a Potential Therapeutic Target in Acute Myeloid Leukemia.
Authors: Amir T. Fathi, Ian Swinnen, Trivikram Rajkhowa, Donald Small, Fredrik Marmsater, John E Robinson, Stefan David Gross, Matthew Martinson, Shelley Allen, Nick Kallan, Mark Levis
Journal: Blood (2009)
Hybrid therapy of late diagnosed esophageal perforation, complicated by mediastinitis and bilateral empyema
Authors: Petko Karagyozov, Tcvetan Minchev, Ivan Tishkov, Ivan Plachkov
Journal: Endoscopy (2017)

An 81-year-old man was admitted to our hospital with clinical deterioration 6 days after diagnostic gastroscopy. Computed tomography (CT) scan showed distal esophageal perforation, bilateral empyema, and a contrast leak into the right pleural cavity ([Fig. 1]). Bilateral video-assisted thoracoscopy was performed, evacuating the empyema, debriding the pleural spaces, and incising the mediastinal pleura. The site of esophageal perforation was located, and mediastinal and pleural drains were placed ([Video 1]). During the same session upper endoscopy was performed, which showed an approximately 12 mm perforation in the distal third of the esophagus. We used an over-the-scope clip (OTSC; Ovesco, Tübingen, Germany) to close the defect. A gastrografin esophagogram performed immediately after clip deployment showed no contrast leak ([Fig. 2]). A fully covered self-expanding metal stent (SEMS; Wallstent; Boston Scientific, Marlborough, Massachusetts, USA) was placed to cover the perforation site after OTSC deployment ([Video 2]).
A Model To Identify Individuals at High Risk for Esophageal Squamous Cell Carcinoma and Precancerous Lesions in Regions of High Prevalence in China
Authors: Mengfei Liu, Zhen Liu, Hong Cai, Chuanhai Guo, Xiang Li, Chaoting Zhang, Hui Wang, Dong Hang, Fangfang Liu, Qiuju Deng, Xin Yang, Wenqing Yuan, Yaqi Pan, Jingjing Li, Chanyuan Zhang, Na Shen, Zhonghu He, Yang Ke
Journal: Clinical Gastroenterology and Hepatology (2017)
A retrospective analysis of integrative medicine consultations at a major cancer center: Reasons for consultation, symptom burden, quality of life, and satisfaction.
Authors: Richard T. Lee, Gabriel Lopez, Jane Williams, Jill Flury, Amica D Onyemeh Sea, Amy Spelman, Bryan Fellman, M. Kay Garcia, Alejandro Chaoul, Kathrin Milbury, Yisheng Li, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2014)

e17630 Background: Many cancer patients use complementary and alternative medicine, but limited data exists regarding the reasons for an integrative medicine consultation and the patient’s symptom burden, quality of life, and satisfaction. Methods: Beginning in September of 2009, all patients receiving an integrative oncology consultation were asked to complete a modified Measure Yourself Concerns and Wellbeing (MYCaW), a modified Edmonton Symptom Assessment Scale (ESAS, 0-10 scale), and a satisfaction rating (0-10 scale). Starting in January of 2013, quality of life was measured by the Patient Reported Outcomes Measurement Information System Global Health (PROMIS-10). Results: A total of 2,564 new patient integrative oncology consultations were conducted from 9/2009 to 12/2013, representing 63% of all consultative visits, with most patients (97.5%, n=2501) completing at least one assessment. About one-quarter of patients (26.0%) had at least one follow-up visit (average 3.1±1.7). The most common reasons for consultation as reported by the MYCaW were integrative approach (32.3%), herbs/supplements (31.9%), nutrition (20.4%), overall health (13.0%), and pain (12.6%). When ranking the importance of the reason for the consultation, 47% marked 10 on a 0-10 points scale for their first reason. Overall satisfaction was rated ≥8 by 94.6% of patients. The highest rated symptoms on the ESAS included poor sleep (mean=4.2), fatigue (4.0), poor memory (3.2), distress (3), and poor appetite (2.8). For the PROMIS-10 (n=711), the standardized T-scores were 43.6 for physical health and 45.8 for mental health (a score of 50 representing healthy population levels). The most common services utilized after the initial consultation were acupuncture (n=1,028) and massage (n = 636). Conclusions: Patients at a major cancer center commonly seek an integrative oncology consultation to address issues of integrative approaches, herbs/supplements and nutrition. Patients had a high satisfaction with the clinical service and reported mild-moderate symptom burden and clinically significant physical health problems.
Subsequent neoplasms in the fifth and sixth decades of life in the Childhood Cancer Survivor Study cohort.
Authors: Lucie Marie Turcotte, John Whitton, Debra L. Friedman, Sue Hammond, Gregory T. Armstrong, Wendy M. Leisenring, Leslie L. Robison, Joseph Philip Neglia
Journal: Journal of Clinical Oncology (2014)

10039 Background: The risk of subsequent neoplasms (SN) in childhood cancer survivors increases over time, but only limited data exist on risk beyond 40 years of age. Methods: Occurrence of SN was evaluated in 3171 5-year adult survivors of childhood cancer ≥40 years of age (median 44 years, range 40-58) following cancer diagnosed <21 years of age, between 1970-1986. Cumulative incidence and standardized incidence ratio (SIR), with corresponding 95% confidence intervals (CI) were used to evaluate risk of SN and subsequent invasive malignant neoplasm (SMN), respectively. SIR were calculated using age-, sex- and calendar year-specific incidence from the NCI Surveillance, Epidemiology and End Results program. Survivors with a history of SN prior to age 40 (SNpos) were also compared to those without previous SN (SNneg). Results: A total of 371 SN were diagnosed ≥40 years of age, including 136 SMN (SIR=2.2, CI 1.9-2.5), 191 non-melanoma skin cancers (NMSC), and 44 meningiomas and other non-invasive neoplasms. Cumulative incidence of a new SN after age 40 was 34.6% (CI 28.7-40.6) at age 55, with SNpos having a higher incidence compared to SNneg 57.6% (CI 46.7-68.6) versus 30.4% (CI 23.8-37). While cumulative incidence of new SMN at age 55 was similar for SNneg and SNpos (15.4% (CI 10.2-20.5) vs. 20.8% (CI 12.5-29.1)), SNpos experienced more NMSC compared to SNneg (cumulative incidence 16.2% (CI 10.8-21.6) vs. 38.2% (CI 27.9-48.5)). Compared to the U.S. population, risk of a SMN was elevated for both SNneg and SNpos (SIR=2.0, CI 1.7-2.4 vs. SIR=3.0, CI 2.2-4.0). Breast cancer was the most common SMN beyond age 40, and also carried the largest risk (SIR=5.5, CI 4.5-6.7). Significantly elevated risks were also seen for renal cancer (SIR=3.9, CI 2.0-7.5), soft tissue sarcoma (SIR=2.6, CI 1.5-4.4) and thyroid carcinoma (SIR=1.9, CI 1.0-3.5). Hodgkin lymphoma (SIR=3.6, CI 3.0-4.4) and radiation therapy (SIR=2.6, CI 2.2-3.1) were associated with high risk of SMN although the magnitude of risk for SNneg and SNposdid not differ substantially. Conclusions: Risk of SN remains significantly elevated after age 40. These data have important implications for screening and should inform anticipatory guidance provided to childhood cancer survivors.
Are Novel Anticoagulants Worth Their Cost?
Authors: Mark A. Hlatky
Journal: JAMA Cardiology (2017)

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Sorafenib and continued erlotinib or sorafenib alone in patients with advanced non-small cell lung cancer progressing on erlotinib: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).
Authors: Victor Gian, Mark S. Rubin, Dianna Shipley, Howard A. Burris, Joseph Kaplan, Rebecca A. Kosloff, Kent C. Shih, Frederick P. Smith, Raven Quinn, Frank A. Greco, John D. Hainsworth, David R. Spigel
Journal: Journal of Clinical Oncology (2012)

7587 Background: Erlotinib is an oral epidermal growth factor receptor kinase inhibitor used in the treatment of advanced non-small-cell lung cancer (NSCLC). Resistance develops in patients (pts) who initially respond to erlotinib leading to progressive disease (PD). Sorafenib is an oral inhibitor of vascular endothelial and platelet-derived growth factor receptors and Raf kinases which play important roles in PD. This randomized phase II study evaluated the role of sorafenib and continued erlotinib or sorafenib alone in pts with progressive NSCLC following initial benefit with erlotinib. Methods: Eligible pts had IIIB/IV NSCLC, an ECOG PS 0-2, and had received ≤2 lines of therapy with the last being single-agent erlotinib. Pts must have PD following clinical benefit (complete/partial response/stable disease) from erlotinib for &gt;8 weeks. Pts were randomized 1:1 to continue erlotinib at the dose administered at the time of PD with the addition of sorafenib 400 mg orally twice daily (Arm A) or to sorafenib alone (Arm B). Cycles were 28 days with restaging every 2 cycles. The primary endpoint was progression-free survival (PFS). Results: 52 pts were enrolled from 2/2008 to 3/2011 (A 24; B 28). Baseline characteristics were balanced between arms and included: median age 65 years (41-87); 65% female; 69% adenocarcinoma/large cell; and 96% PS &lt;2. 41% of pts were either never smokers or smoked &lt;100 cigarettes/lifetime. Pts received a median of 8 weeks of treatment per arm (0.6–67 weeks). The median PFS was 3.1 (95% CI 1.7-3.7) and 2.3 (1.7-3.6) months for A and B, respectively (p=.84). There were no grade 3/4 hematologic toxicities in either arm except grade 3 anemia in 1 pt (A). Severe nonhematologic toxicities in &gt;5% included: fatigue 17%(A)/7%(B); diarrhea 17%/0; dehydration 13%/7%; hand-foot skin reaction 8%/8%, and anorexia 4%/7%. Conclusions: Sorafenib has modest activity when used in combination with erlotinib or as a single agent in pts with PD following benefit with erlotinib alone. Additional study to identify potential subsets of refractory pts who might derive the greatest benefit from sorafenib are warranted.
Association of low socioeconomic status with more aggressive end-of-life care in working-age cancer decedents.
Authors: Yu-Chieh Su, Ching-Chih Lee, Wen-Yao Yin, Chun-Ming Chang
Journal: Journal of Clinical Oncology (2014)

e20500 Background: Previous studies found conflicting relationships between low socioeconomic status (SES) and aggressiveness of end-of-life (EOL) care in older cancer decedents. In this study, we proposed to assess the association between EOL care aggressiveness and SES differences in working-age (over 18 years old and less than 65 years old) cancer decedents from Taiwan between 2009 and 2011. Methods: This population-based, retrospective cohort study used administrative data. A total of 32,800 cancer decedents were identified from the Taiwan National Health Insurance Research Database. The aggressiveness of EOL care was examined by a composite measure adapted from Earle et al., with higher scores indicating more aggressive EOL care. Hierarchical linear regression methods and multilevel logistic regression models were used to explore the association between SES and indicators of aggressive EOL care. Results: Up to 81% of the patients presented at least one indicator of aggressive care. Working-age patients were more likely to receive aggressive EOL care if they were 35-44-year-old men with low-SES, who presented metastatic malignant disease, lived in urban areas, or were in hospitals with more abundant health care resources. In multilevel logistic regression analyses, an association was seen between being high-SES cancer decedents and having had less chemotherapy (P<0.001), fewer ER visits (P<0.001), fewer ICU admissions (P<0.001), and lower rates of dying in acute hospitals (P<0.001) when compared with low-SES cancer decedents. Conclusions: Between 2009 and 2011, working-age cancer decedents in Taiwan continued to receive aggressive EOL care. EOL care was even more aggressive in patients with low-SES. Public health strategies should continue focusing on low-SES patients to provide them with better EOL care.
Self-reported adherence to regorafenib for metastatic colorectal cancer: A retrospective cohort study.
Authors: Kazuyoshi Kawakami, Mitsukuni Suenaga, Azusa Soejima, Kazuo Sugita, Takashi Yokokawa, Kenichi Suzuki, Ayaka Inoue, Yohiaki Machida, Takeru Wakatsuki, Kensei Yamaguchi, Toshihiro Hama
Journal: Journal of Clinical Oncology (2017)

783 Background: Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) and it is frequently involved in various adverse events. The clinical factors affecting adherence to regorafenib remain unclear. The aim of this study is to evaluate adherence to regorafenib in patients with mCRC and to identify candidate factors which might have influence on adherence to regorafenib. Methods: We evaluated 106 consecutively enrolled patients with mCRC who received regorafenib between May 18, 2013 and March 2, 2015 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Adherence to regorafenib was checked by pharmacists using a self-reported treatment diary for patients at a pharmaceutical outpatient clinic. The adherence rate was defined as the number of actual intakes per 21 intakes scheduled in each cycle. We retrospectively surveyed median relative dose intensities of regorafenib and the factors deteriorating adherence across three cycles. Univariate analyses were then performed using patient socio-demographic factors and clinical factor. Multivariate analysis was performed using logistic regression. Significance levels for uni- and multivariate analyses were p &lt; 0.2 and p&lt; 0.05, respectively. Results: A total of 81 patients were evaluated in the study analysis. Adherence rates were 64.4% in the first cycle of regorafenib treatment, 77.4% in the second cycle, and 83.8% in the third cycle. The median relative dose intensity was 57.6%. The most common reasons for non-adherence were hand-foot skin reaction (34.3%, 331 instances), and liver dysfunction (15.3%, 148 instances). In multivariate analysis, increased non-adherence to regorafenib was significantly associated with gender (female) [odds ratio (OR) = 0.20; 95% confidence interval (CI): 0.06-0.68, p = 0.01] and adverse events ( ≥ Grade 3) [OR = 3.16; 95% CI: 1.00-9.97, p= 0.04) in the first cycle.] Conclusions: The high frequency of treatment-related hand-foot skin reaction and liver dysfunction is the main factor affecting adherence to regorafenib. Intensive supportive care in the management of these symptoms could assist adequate adherence to regorafenib.
A phase II randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of simtuzumab (GS-6624) combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.
Authors: Al Bowen Benson, Zung Thai, Michael J. Hawkins, Douglas Werner, Hua Dong, Claudia Lee, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2013)

TPS4149 Background: Lysyl oxidase-like molecule 2 (LOXL2) is an extracellular matrix enzyme that catalyzes the covalent cross-linking of collagen and is widely expressed across desmoplastic tumors. Simtuzumab (GS-6624) is a humanized antibody that specifically inhibits LOXL2 enzymatic activity. Inhibiting LOXL2 is expected to block formation of desmoplasia, which is thought to play an important role in tumor progression and metastasis. Methods: The primary objective and of the study is to compare the additive efficacy of simtuzumab vs. placebo in combination with gemcitabine as measured by improvement in progression free survival (PFS). The secondary objective is to compare the additive efficacy of simtuzumab vs. placebo as measured by overall survival (OS) and objective response rate. Study Design: The study is a randomized, double-blind, placebo controlled Phase 2 trial in subjects with metastatic pancreatic adenocarcinoma. A total of 234 subjects will be randomized to 200 mg simtuzumab, 700 mg simtuzumab, or placebo at a 1:1:1 ratio (78 subjects per treatment group) in combination with gemcitabine in cycles of 28 days. In each cycle, subjects will receive IV GS-6624 or placebo infused on Days 1 and 15, and IV gemcitabine (1000 mg/m2) on Days 1, 8, and 15. CT or MRI scans will be performed every 8 weeks to evaluate response to treatment. Subjects will continue courses of treatment every 28 days in the absence of disease progression or unacceptable toxicity. As of January 30, 2013, 162 subjects have been randomized. Clinical trial information: NCT01472198.
Should adjuvant zoledronic acid be used in early-stage, endocrine-sensitive breast cancer?
Authors: Nathan William Dana Lamond, Chris Skedgel, Daniel Rayson, Tallal Younis
Journal: Journal of Clinical Oncology (2013)

e17564 Background: Adjuvant zoledronic acid (ZA) appears to improve disease-free survival (DFS) in women with endocrine-sensitive breast cancer and low estrogen levels (LEL) including post-menopausal women, and pre-menopausal women treated with LHRH agonists. ZA, however, is also associated with potential adverse events and incremental drug acquisition costs. An overall assessment of the long-term clinical and economic impacts of adjuvant ZA may therefore help guide the decision to adopt this novel therapeutic option. We examined the incremental quality-adjusted life-years (QALY) and costs per QALY associated with adjuvant endocrine treatment plus ZA relative to endocrine treatment without ZA in women with endocrine-sensitive breast cancer and LEL. Methods: A generic state-transition model was developed to compute cumulative costs, from a Canadian perspective, and QALY associated with and without adjuvant ZA (4 mg IV qM*3→ q3M*8 → q6M*5) over a 25-year horizon for women with endocrine-sensitive breast cancer and LEL. Costs, utilities, DFS and adverse events were derived from relevant clinical trials, the literature and local resources. One-way and probabilistic sensitivity analyses were conducted for key model parameters. Results: Adjuvant ZA was associated with incremental QALY gains of 0.80 and 0.52 and resultant CU estimates of $3,571 and $7,683 per QALY gained in pre- and post-menopausal women, respectively. CU estimates were robust across reasonable uncertainty ranges in all parameters. Conclusions: Adjuvant ZA appears to be associated with long-term QALY gains in women with endocrine-sensitive breast cancer and LEL as well as CU estimates that are well below commonly accepted North American thresholds. The favourable long-term clinical and economic impacts observed in this study further support the use of adjuvant ZA in this setting.