tbuckley/cabot-search huggingface dataset:
The relationships of reduction in pain with other symptoms for cancer patients treated with stereotactic body radiation therapy.
Authors: Tito R. Mendoza, Xin Shelley Wang, Laurence D Rhines, Ugur Selek, Hadley J. Sharp, Charles S. Cleeland, Eric L. Chang
Journal: Journal of Clinical Oncology (2013)

e17588 Background: Radiotherapy attenuates pain in patients with spinal metastases. A newer technology is stereotactic body radiotherapy (SBRT) that allows for high dose radiation to be accurately given to a target while sparing nearby tissues. Although a previous study reported improvement in pain, fatigue, disturbed sleep, drowsiness, sadness, fatigue, distress, lack of appetite, nausea, and difficulty remembering after SBRT, it did not examined the quantitative relationship of pain reduction with improvement in symptom burden. Methods: Cancer patients (n=149) with mechanically stable, non–cord-compressing, spinal metastases (n=166) were treated by SBRT in a phase I/II study. Patients received a total dose of 27–30 Gy, typically in three fractions. Symptoms were measured repeatedly using the M. D. Anderson Symptom Inventory (MDASI). Linear mixed model was fitted with pain as the dependent variable and other symptoms as predictor variables to determine the effect of other symptoms on pain throughout the treatment trajectory. Opioid use was a covariate in the analysis. Results: As reported previously, there were significant reduction in pain (p=0·00003) disturbed sleep, drowsiness, sadness (all p&lt;0·0001), fatigue, distress, lack of appetite, nausea, and difficulty remembering (all p&lt;0·05) during the six months post-SBR. Based on our linear mixed models, a 1-point reduction in fatigue (p&lt;.001) is associated with 0.26 reduction in pain. Similarly, a 1-point reduction in in sleep disturbance (p&lt;.001), numbness (p&lt;.001), distress (p&lt;.005), lack of appetite (p&lt;.01) and dry mouth (p&lt;.03) were associated with reductions of 0.25, 0.22, 0.16, 0.15, and 0.14 in pain, respectively. Opioid use was significantly reduced after SBRT. Conclusions: Significant reduction in pain from SBRT is associated with improvement in symptom burden. These findings may provide insights into how symptoms are interrelated during cancer treatment.
Conversion surgery for unresectable gastric cancer following complete response of distant metastasis by systemic chemotherapy.
Authors: Daisuke Kobayashi, Mitsuro Kanda, Chie Tanaka, Naoki Iwata, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2017)

152 Background: In case of gastric cancer (GC), conversion surgery (CS) can be defined as resection of the primary cancer by gastrectomy which had not been originally planned but was indicated after confirming complete response (CR) in the distant metastasis (DM) by chemotherapy. In the present study, we looked at prognostic significance of CS, which is intended to cure originally unresectable GC. Methods: From 2004 to Feb in 2016, 24 GC patients who were treated by chemotherapy and achieved CR in DM underwent CS among 909 patients with gastrectomy in our department. 10 out of 24 patients who had peritoneal metastases (P) as a single non-curative factor underwent intraperitoneal chemotherapy (IP) in addition to systemic chemotherapy. CR was confirmed by CT and/or laparoscopic examination. Results: 15 patients had P, 13 had distant lymph node metastases (LYM), 2 had liver metastases, and 2 had lung metastases. Chemotherapeutic regimens consisted of systemic chemotherapy plus IP of taxane in 10 patients, S-1/CDDP in 7, capecitabine/CDDP/trastsuzumab in 3, and others in 4. Median duration of chemotherapy before surgery was 7.3 months (2.3-17.5). Total gastrectomy was performed in 18 patients and distal gastrectomy in 6, achieving R0 resection in 21 patients and R1 in 3. 10 patients with P who underwent IP relapsed within 12 months postoperatively except for 2 and had significantly shorter overall survival time than those with other DM except for P (median: 20 vs. 42 months, P = 0.004). Among 14 patients who had DM other than P as target lesions, 9 are disease-free with postoperative median follow up time of 35 months (6.8-82), and 5 patients had recurrence (LYM in 4 and P in 1) with postoperative median survival time of 25 months (4.8-45). DM of the patients without recurrence had achieved CR within shorter period (median: 3.6 vs. 6.7 months) and had higher pathological response rate of the primary lesion (89% vs. 40%) compared to patients with recurrence. Conclusions: Outcome of GC patients who underwent CS after achieving CR in DM was promising, especially in those without P. Further issues such as appropriate chemotherapeutic period, and prognostic factors to decide on the indication for CS need to be solved.
Clinical destiny of indeterminate pulmonary nodules in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.
Authors: David B. Cahn, Brian McGreen, Albert Lee, Elizabeth R. Plimack, Daniel M. Geynisman, Matthew R. Zibelman, Benjamin T. Ristau, Marc C. Smaldone, Richard E. Greenberg, Rosalia Viterbo, David Chen, Robert G. Uzzo, Alexander Kutikov
Journal: Journal of Clinical Oncology (2017)

297 Background: Perioperative risks and significant quality of life concerns following radical cystectomy (RC) render accurate pre-operative staging paramount, since metastatic patients are unlikely to benefit from extirpation. Yet, incidental indeterminate pulmonary nodules (IPNs) are a common pre-operative finding in clinical practice, thus representing a significant management challenge. As such, we sought to evaluate the natural history of IPNs in a large institutional cohort that underwent RC. Methods: We reviewed our institutional database for patients who underwent RC from 2000 through 2014 for urothelial carcinoma (UCC) of the bladder and had at least 1 identifiable pulmonary lesion on preoperative staging imaging measuring &lt;2cm in any axis. Patients who were M1 at surgery, had gynecologic, colorectal, or missing pathology, or non-urothelial histology were excluded. We sought to determine the natural history of these pulmonary lesions and evaluated predictors of metastatic etiology. Results: During the study period, 681 RC were performed at our institution. We identified 73 patients with an identifiable preoperative IPN who met inclusion criteria and underwent RC. In this subset, 23.3% were female, 21.9% were active smokers, and 54.8% former smokers. The median age at surgery was 70±8.6 years. Nearly half (49.3%) received neoadjuvant chemotherapy. 61.6% of RC were performed using the traditional open approach, while 38.4% were performed robotically. Final pathologic staging included 16.4% pT0N0Mx, 19.2% pTa/Tis/T1N0Mx, 42.5% pT2-4N0Mx, and 21.9% pTanyN+Mx. Median IPN size was 0.7±0.3cm. At median follow up of 23.5±21.9 months, 93% (68/73) of IPNs in our cohort were clinically benign, with metastatic urothelial cancer confirmed in only 4 patients, and a primary lung malignancy diagnosed in 1 patient. Conclusions: The majority of IPNs in patients who proceeded to RC for UCC of the bladder were stable upon follow-up and rarely represented malignancy. As such, in appropriately screened UCC patients, IPNs should not be a barrier to proceeding with extirpative surgical therapy.
Congestive heart failure (CHF) in acute myeloid leukemia patients during induction.
Authors: Priyanka Raval, Vamsi Kota, Yousef Zakharia, Giovani Carter, Kala Christopherson, Farrukh Tauseef Awan, Jeremy Mark Pantin, Anand P. Jillella
Journal: Journal of Clinical Oncology (2013)

7105 Background: Leukemia induction treatment is associated with significant morbidity and mortality. Myocardial stunning may be a result of chemotherapy as well as cytokines released from lysis of tumor cells leading to drop in ejection fraction (EF). When CHF is associated with sepsis, it may result in increased mortality. We report the incidence of CHF in leukemia patients undergoing induction. Methods: We performed a retrospective chart review on patients diagnosed with AML including acute promyelocytic leukemia (APL), who received chemotherapy between December 1, 2004 and December 31, 2012 at Georgia Regents University. Baseline and follow up EFs were recorded by echocardiogram or nuclear medicine scan. We evaluated patients who had a drop in EF after the first or subsequent inductions. We excluded patients who had a delayed drop in EF. Results: 217 consecutive patients with AML with normal ejection fraction at diagnosis were evaluated. 18 patients (8.2%) demonstrated a decrease in EF. This included 14 patients with AML and 4 with APL. 15 patients received one cycle of induction, 2 received re-induction and 1 was treated for relapsed disease. 2 patients did not receive anthracyclines(ACs). Median age of patients with CHF was 57 years (range 29-75). The median drop in EF was 23% (10-45%). Median days from the start of treatment to the observed drop were 25 (5-109). 6 patients are alive with median survival of 175 days. Overall, 5 out of 18 patients recovered their cardiac function with a median survival in these patients of 1,173 days. In 13 patients without recovery in EF survival was only 71 days. Conclusions: Chemotherapy by itself and cytokines released from treatment may result in reversible drop in EF in some patients and a persistent drop in the others. Re-induction is essential in a significant proportion of patients and ACs are commonly used that puts them at an increased risk for CHF. We propose that repeat cardiac evaluation, especially in patients getting re-induced, is necessary for identifying patients with cardiac abnormalities to prevent further cardiac injury and increased mortality.
Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants
Authors: Carmel T. Collins, Maria Makrides, Andrew J. McPhee, Thomas R. Sullivan, Peter G. Davis, Marta Thio, Karen Simmer, Victor S. Rajadurai, Javeed Travadi, Mary J. Berry, Helen G. Liley, Gillian F. Opie, Kenneth Tan, Kei Lui, Scott A. Morris, Jacqueline Stack, Michael J. Stark, Mei-Chien Chua, Pooja A. Jayagobi, James Holberton, Srinivas Bolisetty, Ian R. Callander, Deborah L. Harris, Robert A. Gibson
Journal: New England Journal of Medicine (2017)

Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking.We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first.A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06).Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).
Association of smoking with pulmonary recurrences among women with intermediate- to high-risk early-stage endometrial adenocarcinoma.
Authors: Lori Elizabeth Weinberg, Kristine M. Zanotti, Charles Kunos
Journal: Journal of Clinical Oncology (2012)

5089 Background: While a number of histologic risk factors have been identified in endometrial carcinoma, host factors are less well studied. Our aim was to examine the influence of smoking on the risk of pulmonary recurrences in women with early stage intermediate to high-risk endometrioid uterine cancer (EC). Methods: Women with surgically treated stage I or II EC from 1994 to 2010 were included in this study if they had lymphovascular space invasion (LVSI), FIGO grade 2 or 3 histology (G2/3), or outer half myometrial invasion (OI). All demographic, medical and oncologic data were obtained from chart review. Patients were excluded if their follow-up period was less than six months or if they had a diagnosis of a second primary invasive cancer. We performed univariate and multivariate logistic regression analyses and Fisher’s Exact test for two-way analyses of categorical variables to identify prognostic factors of pulmonary recurrences. Significance was determined by two-sided tests with α=0.05. Results: 349 patients were identified to meet histologic criteria, 3% were excluded. The remaining 337 patients had a median follow-up of 60 months (range 6 to 194). The median age of this cohort was 68 years and median BMI was 30.7 kg/m2. 81 patients (24%) had a past or present history of smoking. There were 14 pulmonary recurrences (4.1%), 36 (10.7%) distant recurrences and 58 (17.2%) total recurrences in the cohort. Smoking (present or past) was significantly associated with pulmonary recurrences, with an odds ratio of 1.09 (95% CI 1.04-1.15; P=0.0002). In a multivariate analysis adjusting for age, BMI, grade, LVSI, OI, cervical invasion, and adjuvant therapy, smoking was still a predictor of pulmonary recurrences. Conclusions: Smoking is a significant and independent predictor of pulmonary recurrences among women with early stage EC. Refining our understanding of host factors that influence risk may further allow us to identify those who may benefit most from adjuvant therapies as well as intensive surveillance.
Combined analysis of three randomized phase III trials comparing S-1 monotherapy and S-1 combination therapy for first-line treatment of advanced gastric cancer.
Authors: Madoka Takeuchi, Wataru Ichikawa, Kohei Shitara, Yu Sunakawa, Koji Oba, Hirofumi Michimae, Everardo D. Saad, Wasaburo Koizumi, Yuh Sakata, Hiroshi Furukawa, Marc E. Buyse, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2017)

49 Background: S-1 is the gold standard for first line therapy of advanced gastric cancer in Asia. There have been multiple meta-analyses published researching and comparing the efficacy and safety of S-1 monotherapy versus combination 1,2 . However there has been no analysis using actual trial data. Methods: Actual data from three randomized Phase III trials were combined to compare the efficacy of S-1 Monotherapy and S-1 combination therapy. The START trial, comparing S-1 and combination S-1 with docetaxel, SPIRITS, comparing S-1 and combination S-1 with cisplatin and TOP-002, comparing S-1 and S-1 combination with irinotecan, were merged and combined. For this analysis, the three S-1 arms were combined (n = 642) and the different S-1 combination therapy were combined (n = 617) creating two new treatment arms. The primary efficacy outcome of overall survival, progression free survival and subset analysis of overall survival stratified by baseline characteristics were performed. Results: A total of 1248 patients, including 210 Korean patients from the START were used in the analysis. The median overall survival days for S-1 combination and monotherapy was 382 [209, 648] and 321 [177, 597] and median progression free survival days for S-1 combination and monotherapy was 153 [81, 267] and 122 [61, 204]. Both overall survival (p = 0.0088 HR = 0.85 (0.76,0.96)) and progression free survival ( p = &lt; 0.001 HR = 0.75 (0.67,0.85)) was significantly longer in the combination therapy arm compared to the monotherapy arm. Conclusions:Although there are limitations, the analysis re-confirms that S-1 combination therapy shows to be more efficacious compared to S-1 monotherapy for advanced gastric cancer patients. It must be noted that heterogeneity of the S-1 arm was not carefully considered when combining the S-1 data for the trials. In addition, the results are limited to the Asian (Japanese and Korean) population.
Assessment of HER2 status from an epidemiology study in tumor tissue samples of gastric and gastro-esophageal junction cancer: Spanish results of the HER-EAGLE study.
Authors: Lourdes Gomez, Angel Concha, Tomas Garcia-Caballero, Jose Ignacio Busteros, Emilio Burgos, Maria Company, Stefania Landolfi, Irune Ruiz, Joaquin Gonzalez-Carrero, Rosa Maria Ortiz Duran, Jose Ibanez Martinez, Carmen Martinez, Mar Iglesias, Maria del Pino Florez, Isabel Peligros, Rufo Rodriguez, Eva Musulen, Paola Beatriz Leon, Juan Francisco Parra, Felip Vilardell
Journal: Journal of Clinical Oncology (2012)

4089 Background: Overexpression of HER2 is an important biomarker in gastroesophageal junction (GEJ) and gastric cancer (GC) and a predictive factor for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit in overall survival of adding trastuzumab to chemotherapy inHER2-positive advanced GEJ/GC patients, following validated scoring criteria by a central laboratory. This study examines the incidence of HER2 positivity (local laboratories) in GEJ/GC according to EMA Herceptin label. Methods: HER-EAGLE was an epidemiological, non–interventional, international study assessing HER2 status by IHC/ISH in tumor samples from any stage GEJ/GC patients. Neutral buffered 10% formalin embedded tissues (surgical excision specimens or minimum 6-8 biopsies) analyzed via validated Ventana and Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+. Overall and subgroup estimates calculated with 95%CI. Data from the Spanish cohort are presented. Results: The Spanish cohort of HER-EAGLE included 1,954 participants (63.7% males) from 33 hospitals (Dec2010 to Aug2011), with 469 biopsies (24.0%) and 1,479 excisions (75.7%). Samples were 13.7% GEJ and 86.3% GC, and the adenocarcinomas were 1,137 intestinal (58.2%), 510 diffused (26.1%), 163 mixed (8.3%; Laureen classification), and 144 not available (7.3%). Median time from sampling to HER2 analysis of 5.1 years (range from days to 12 years). Total of 210 cases tested IHC 3+ (10.7%), 215 IHC 2+ (11.0%), 308 IHC 1+ (15.8%), and 1,221 IHC 0 (62.5%). Overall, HER2 positivity (IHC 3+ or IHC2+/ISH+) was 14.1% (95%CI 12.61 – 15.75). HER2 positivity by histological type was higher in intestinal adenocarcinomas (19.5%) compared to diffused (4.5%) or in mixed (9.2%). Conclusions: HER-EAGLE confirmed the feasibility of community based HER2 testing in GC as the first study with a high number of samples analyzed by local laboratories. The incidence of HER2-positivity (EMA label definition) was similar to the ToGA screening population, and it was again higher in adenocarcinomas of intestinal type (19.5%).
Genome-wide analysis and characterization of an online sarcoma cohort.
Authors: Kimberly E Barnholt, Chuong B Do, Amy K Kiefer, Marisa Nelson, Judy Ellen Garber, Mark E. Robson, Robert G. Maki, George D. Demetri, Anne Wojcicki
Journal: Journal of Clinical Oncology (2012)

10097 Background: Recruitment of an adequately sized cohort for genome-wide studies presents a serious challenge for rare diseases such as sarcoma. Traditional barriers to participation include proximity of clinical centers and motivation or ability to travel. 23andMe’s web-based platform provides increased accessibility to research participation, facilitating rapid recruitment of patients (pts) and enabling a large-scale genome-wide association study (GWAS) of sarcoma. Methods: Sarcoma pts were recruited through web and email campaigns, patient advocacy groups, physician offices, and events. Pts provide IRB-approved consent, complete surveys, and receive updates about research progress through an online account. In collaboration with an uncompensated panel of academic experts, an online survey was developed to collect patient-reported data on diagnosis, family history, symptoms and treatment. Results: This web-based approach has accrued the largest genotyped, recontactable sarcoma cohort to date. In 20 months, 772 sarcoma pts have enrolled, 683 have been genotyped and 611 have provided data online. The cohort is primarily of European ancestry (92%), disproportionately female (72%), with an average age of 51 (± 15 years). More than 88% of pts indicated a soft tissue sarcoma diagnosis, with leiomyosarcoma, liposarcoma and “malignant fibrous histiocytoma” being the most commonly reported subtypes. Over 36% of pts report undergoing active treatment of some type. Association scans were conducted across a set of 8,058,452 imputed SNPs, using 568 unrelated sarcoma cases of European ancestry and &gt;70,000 unrelated population controls from the 23andMe database. Initial results have identified no significant genome-wide associations for general sarcoma risk, despite having &gt;90% power to detect risk variants with &gt;5% minor allele frequency and odds ratio &gt;2.5, suggesting the absence of common variants with strong shared effects across sarcoma subtypes. Conclusions: This pilot study demonstrates feasibility of rapid recruitment and longitudinal engagement of pts through online technology. Such techniques may significantly accelerate, and in some cases fully enable, large-scale genomic studies of sarcoma and other rare diseases.