tbuckley/cabot-search huggingface dataset:
Kaposi sarcoma: A retrospective review.
Authors: María Ángeles Vaz Salgado, Ainhoa Madariaga Urrutia, Maria Eugenia Reguero, Ignacio Gallego, Federico Longo, Carmen Guillén Ponce, Reyes Ferreiro Monteagudo, Mercedes Rodríguez Garrote, Vanessa Pachón Olmos, Ana Gomez, Jacobo Muñoz del Toro, Alfredo Carrato
Journal: Journal of Clinical Oncology (2015)

e21520 Background: Kaposi Sarcoma (KS) is a lymphoangioproliferative disease, related to immunodeficiency and may be associated with human herpes virus 8 (HHV-8). KS is classified into four types: classic CKS, iatrogenic, endemic and AIDS-related (AIDS-KS). There is no consensus on the optimal tumor-directed therapy in different KS. Methods: A retrospective analysis of 76 patients treated at a University Hospital between 1998 -2014. A histological diagnosis of KS was required. Results: Forty three percent were CKS, 47% AIDS-KS and 10% post-tranplantation. At diagnosis, the median age was 58 years (y) (CKS 76y (39-95); AIDS-KS 44y (21-79), post-trasplantation 58y (53-65)), with a prevalence in men (82%). KS lesions were presented primarily on the skin (69%), also mucosa (13%), lymph nodes (5%) and visceral involvement (13%). 21% had some kind of other neoplasia than KS. In CKS 80% had only skin lesions, mainly with plaque appearance (48%) and 40% were treated with surgery. Median overall survival (OS) was 12y (CKS 8.9y, AIDS-KS not reached, post-transplantation 2.8y);and median progression free survival was 9.5y (CKS 4.5y, AIDS-KS 12y, post-transplantation not reached). Twenty percent of the patients received systemic treatment as the first approach, whereas for the rest it was local treatment. 28% of patients received systemic therapy at some point of the disease and 70% of patients with visceral involvement. All AIDS-KS patients were treated mainly with pegylated liposomal doxorubicin and everolimus. There was a slight trend between a higher OS and the use of systemic treatment (p: 0.4). Conclusions: KS patients are heterogenic, showing most of them several comorbidities. In most cases KS may be indolent but in some cases may be aggressive. Although there is a prevalence of localized disease, systemic treatment is part of the treatment. There are no consensus about the best regimen and more studies are needed to improve the treatment of these patients.
Structure of a physician assistant (PA)-managed survivorship practice within a multidisciplinary breast clinic
Authors: B. A. Moore, D. W. Northfelt
Journal: Journal of Clinical Oncology (2006)

6087 Background: In the last two decades, success in breast cancer screening and treatment has resulted in evolution of a growing patient population with unique medical needs. The American Cancer Society currently estimates a 98% relative five-year survival rate for patients with localized breast cancer, 88% for all stages combined. Caring for survivors represents both opportunity and challenge for the medical community. The integrated team approach in a multidisciplinary breast center is the ideal model to incorporate PAs in providing comprehensive long-term surveillance and support in this setting. Methods: The core mission of a PA-managed survivorship practice is outlined as follows: Maximize health and quality of life in breast cancer survivors, recognizing physical, psychological and spiritual factors; Provide early detection of disease recurrence and/or new breast cancer occurrence in women with a breast cancer history; Aggressively manage and overcome problems resulting from breast cancer treatment; Aid women in understanding and overcoming risks, including genetic risks, for developing breast cancer. Evidenced-based algorithms defining standards of care create the foundation for clinical decision making and establish precedent for continuity of care. The scope of care is enhanced by opportunities to incorporate research and genetic counseling. Results: Of 205 patients seen between 9/1 and 12/31/2005, 48% were younger than 70, 55% were Stage I, 82% were less than 5 years post-treatment, 63% were on hormone therapy. Conclusions: With continued trends in breast cancer survival, specialized long-term surveillance and support is essential to providing quality, comprehensive care that addresses the unique medical needs of these patients. A PA-managed breast cancer survivorship practice within a multidisciplinary breast clinic not only provides forum for such endeavors, but also fosters opportunity for life-long partnership focusing on quality of life, health and well-being. [Table: see text] No significant financial relationships to disclose.
AR amplification eradication with high-dose testosterone (T) in patients with heavily pretreated mCRPC.
Authors: Patrick Cotogno, Elisa M. Ledet, Joshua Schiff, Charlotte Manogue, Brian E. Lewis, Oliver Sartor
Journal: Journal of Clinical Oncology (2017)

251 Background: Patients (Pts) with mCRPC resistant to novel hormones (abi/enza) and taxanes pose a challenge for clinicians. Typically, once these agents are exhausted, clinical trials represent the best therapeutic option; however, many pts are not appropriate for clinical trials due to marrow suppression and/or extensive pre-treatments. Herein we present limited experience with three pts treated with high dose T when therapeutic clinical trial options were not available. Methods: Data was retrospectively collected at Tulane Cancer Center for pt treatment history, laboratory parameters, and circulating free-DNA genomic testing. High dose testosterone was used at a dose of 87.5-100 mg given daily as a 1% testosterone gel applied to the skin. Results: All the mCRPC patients were pre-treated with abi, enza, taxanes, &amp; radium-223. All pts had RBC transfusions due to marrow suppression. All patients were previously treated on clinical trials. After starting high dose T, pt 1 demonstrated a clinical improvement in energy and appetite with a PSA decline from 530 to 45.8 ng/ml (-91.4%) over 30 days. At baseline, cfDNA analyses measured 15.9X AR amplification and 3.7X MYC amplification. The cfDNA also contained 9.8% of P53R273H mutation. Post high-dose T (serum T from castrate to 1462 ng/dL), both of the cfDNA measured amplifications returned to normal and P53 mutation declined to 0.5%. The PSA nadir occurred 30 days after T start; T was stopped 96 days after starting because of PSA rise to 280 ng/ml. The pt then restarted abi, despite prior resistance, and PSA declined from 280 to 65 ng/ml (-76.6%). The 2 other patients had PSA increases and clinical deterioration and high dose T was stopped after 2-3 weeks. Conclusions: Response to high dose T has been reported in occasional case reports going back over 60 years ago (see Brendler H et al. Arch Surg 1950;61:433–40). The frequency of favorable responses is unknown. In one case, a reversal of AR and MYC amplification was observed. The responding patient then was re-sensitized to abi, a drug to which he was previously resistant. Further research, such as the TRANSFORMER trial, is needed to understand the molecular changes and treatment options for this population.
Superior survival in children with rhabdomyosarcoma treated as per IRSG compared to as per SIOP regimen.
Authors: LeLe Aung, Aung Soe Tin, Thuan Chong Quah
Journal: Journal of Clinical Oncology (2012)

e20003 Background: Rhabdomyosarcoma (RMS) constitutes nearly 4% of all children diagnosed with cancer in ethnically diverse small island city of Singapore (pop. 5 million). Methods: We compared 56 children with RMS from April 1993 to December 2010 from KK Women’s and Children’s Hospital and National University Hospital, Singapore. They were treated as per Intergroup Rhabdomyosarcoma Study Group (IRSG) regimen (n=25), Société Internationale Pediatrique D’Oncologie (SIOP) regimen (n=20), and various other regimens (n=11). Results: Median age of diagnosis was 6.3 (0.1 - 17.3 years) with a median follow-up of 2.5 (0 - 15.6 years). According to IRSG classification, there were 19 (35.1%) with low risk (LR), 21 (38.8%) with intermediate risk (IR) and 14 (25.9%) with high risk (HR) disease. Fifteen (26.8%) were alveolar subtype, 23 (41.1%) were embryonal and sub-classification was not available in 18. The primary sites of tumor were: head and neck (n=22); genitourinary (n=19); extremity (n=10); and abdomen (n=5). At the time of analysis, 80.0% (n=45) were alive with no evidence of disease, 9 were dead of disease, and two were alive with disease. The 5-year EFS and OS for the cohort was 81.8% and 80.3% respectively. By disease risk group, 5-year EFS for LR was 93.3% [95% CI, 88.9 – 98.5], IR at 94.4% [95% CI, 90 – 99.6] and HR at 42.9% [95% CI, 41.5 – 47.7] respectively (p&lt;0.001). The 5-year EFS for risk group by chemotherapy received per SIOP vs. per IRSG revealed: LR- 100% vs. 90.0% (p=0.43); IR- 100% vs. 90.9% (p=0.40); HR- 0% vs. 57.1% (0.64) respectively. Of 16 (7= HR) relapses at median of 2 years, 4 of 4 treated as per SIOP regimen were dead of disease and 2 of 3 treated as per IRSG were alive at last follow-up. Conclusions: High risk disease treated as per IRSG regimen resulted in superior EFS and OS than per SIOP. Although relapsed disease can be salvaged after initial therapy using SIOP regimen, emotional and financial impact of disease relapse on the family is vast. It would be of interest to report whether our findings can be duplicated in a collaborative international study.
An evaluation of the drug interaction potential of netupitant with substrates, inhibitor and inducer of CYP3A4.
Authors: Klaus Peter Kammerer, Giorgia Rossi, Selma Calcagnile, Wolfgang Timmer
Journal: Journal of Clinical Oncology (2012)

e19533 Background: Neurokinin-1 receptor antagonist (NK 1 RA) is commonly administered in combination with a 5-HT 3 RA such as palonosetron (PALO) to prevent the stimulus of nausea and vomiting caused by emetogenic chemotherapy. Netupitant (NETU), a new NK 1 RA under evaluation for its antiemetic efficacy and tolerability, is both a substrate for and a competitive inhibitor of CYP3A4. Two studies were designed to determine the potential risk for drug-drug interaction in clinical practice. In the first study, the effects of NETU on the metabolism of two representative CYP3A4 substrates, erythromycin (ERY) and midazolam (MID) were determined. In the second study, a CYP3A4 inhibitor, ketoconazole (KETO), or an inducer, rifampicin (RIF) was coadministered with a fixed dose combination of NETU/PALO to observe the potential effects on NETU and PALO metabolism. Methods: Serial blood samples were collected from healthy volunteers and pharmacokinetic (PK) parameters were determined in both studies. The first trial was a 3-period crossover performed in 20 subjects receiving NETU (300 mg), ERY (500 mg) or MID (7.5 mg). The second trial was a 2-way crossover in 36 subjects receiving a single dose of NETU/PALO (300 mg/0.5mg, Day 1) administered as a fixed dose combination and KETO (400 mg QD, from Day-2 to Day 10) or RIF (600 mg QD from Day -7 to Day 10). Results: NETU, by inhibiting the CYP3A4, increased Cmax and AUC parameters by 40% and 130%, respectively, when administered with MID and by 30% when administered with ERY. KETO increased NETU AUC by 140% and Cmax by 25%, while RIF decreased NETU AUC by 83% and Cmax by 62%. A decrease of 19% was observed in PALO AUC when administered with RIF, while KETO had no relevant effect on PALO PK. Conclusions: The results of these studies suggest that the coadministration of NETU with drugs that are substrates, inhibitors, or inducers of the CYP3A4 enzymes, may require dose adjustments. These results are in line with pharmacokinetic data of aprepitant, the only commercially available NK 1 RA. The effect of RIF on PALO is not considered clinically relevant. Treatments were well tolerated in all studies.
<i>PPP1R13L </i>variant as a prognostic factor in patients with rectal cancer.
Authors: Yee Soo Chae, Jong Gwang Kim, Sang Kyun Sohn, Soo Jung Lee, Byung Woog Kang
Journal: Journal of Clinical Oncology (2012)

e14074 Background: Genetic variants related with apoptosis and DNA repair pathways may play a meaningful role in cancer progression as well as carcinogenesis. Among them, PPP1R13L and ERCC1 polymorphisms was found to synergistically affect these pathways. The aim of this study was to investigate the association between these genetic variants and prognosis of colorectal cancer (CRC) operated curatively. Methods: A total of 349 CRC patients underwent curative surgery between March 2003 and August 2006 were consecutively enrolled. DNA was extracted from fresh frozen normal tissue and each polymorphism (PPP1R13L rs1005165 and rs967591; ERCC1 rs11615 and rs735482) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: No statistical significance between these 4 variants and survival in a multivariate analysis for all CRC patients. However, the CC genotype of the PPP1R13L rs1005165 was significantly associated with worse survival in 164 patients with rectal cancer (HR = 2.10 and p = 0.037 for RFS; HR = 2.27 and p = 0.039 for DSS, respectively) as a recessive model of the C allele in a multivariate analysis. Meanwhile, no statistical differences in clinicopathologic characteristics were observed according to the rs1005165 genotype in rectal cancer patients. Conclusions: Our results suggest that PPP1R13L variant is possible prognostic marker in Korean patients with operated rectal cancer.
Cardiovascular mortality (CVM) among testicular nonseminoma (TN) survivors after chemotherapy (CHEM) or surgery (SURG).
Authors: Chunkit Fung, Sophie D. Fossa, Michael T. Milano, Deepak M. Sahasrabudhe, Lois B. Travis
Journal: Journal of Clinical Oncology (2014)

9593 Background: Increased long-term risks of cardiovascular (CV) disease after CHEM for testicular cancer are well established whereas few studies have quantified the association of cisplatin-based chemotherapy with arterial thromboembolic events (ATE). We examined CVM in a large population-based cohort of TN survivors managed with modern combination CHEM, which usually includes cisplatin. Methods: Standardized mortality ratio (SMR) of CVM stratified by time since TN diagnosis were calculated for 15,006 TN survivors reported to the SEER program (1980-2010) initially managed with CHEM (n=6,909) or SURG (n=8,097) alone without RT, with each cohort accruing 60,065 (median 6.5) and 81,227 (median 7.9) person-years (PY) of follow up, respectively. Results: After CHEM, significant excesses of CVM occurred (n=54; SMR 1.4; 95% CI 1.03-1.8; absolute excess risk (AER) 2.4 per 10,000 PY) including deaths from heart disease (n=42; SMR 1.3; 95% CI 0.9-1.7), cerebrovascular disease (CVA) (n=10; SMR 2.4; 95% CI 1.2-4.4) and other arterial diseases (n=2; SMR 6.5; 95% CI 0.8-23.5). Excess CVM was concentrated within 1 yr after diagnosis, with SMRs during the <1, 1-4, 5-9, 10-14, 15-19 and 20+ yr periods 5.3 (95% CI 2.7-9.5), 1.7 (95% CI 0.9-2.9), 1.2 (95% CI 0.6-2.2), 0.9 (95% CI 0.4-1.9), 1.2 (95% CI 0.5-2.3), and 0.8 (95% CI 0.3-1.7), respectively. In particular, significantly elevated 4- to 22-fold risks of mortality due to either heart disease (n=6; SMR 3.5; 95% CI 1.3-7.5) or CVA (n=5; SMR 21.7; 95% CI 7.1-50.7) occurred in the <1 yr period. In contrast, among those managed with SURG only, no excess deaths were observed, either for all CVM taken together (n=50; SMR 0.8; 95% CI 0.6-1.1), heart disease (n=43; SMR 0.8; P>0.05) or CVA (n=7; SMR 1.07; P>0.05). Univariate Cox regression analysis showed excesses of CVM after CHEM vs. SURG (hazard ratio 1.5; 95% CI 1.01-2.2). Conclusions: Early ATE associated with modern CHEM may in part explain the excess deaths due to heart disease and CVA during the <1 yr period. Future analytic studies should not only quantify temporal trends of CV disease incidence and CVM in TN survivors, but include mechanistic investigations to facilitate the development of preventive efforts.
Risk factors for anthracycline-associated cardiotoxicity.
Authors: Raquel E. Reinbolt, Roshan Patel, Xueliang Jeff Pan, Cynthia Dawn Timmers, Robert Pilarski, Charles L. Shapiro, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2014)

e20583 Background: Genomic predictors of anthracycline (AC) cardiotoxicity are under investigation. Carbonyl reductase (CBR) catalyzes anthracycline metabolism and single nucleotide polymorphisms (SNPs) in CBR impact metabolic efficiency. In pediatric patients, homozygosity for the major allele (G) in the CBR3 gene was associated with increased risk for AC cardiomyopathy. We hypothesized that CBR SNPs contribute to cardiotoxicityin adults. Methods: We retrospectively identified female breast cancer patients in the Columbus Breast Tissue Bank Registry treated with AC from 2003-2012. We selected patients who developed cardiomyopathy, defined as a drop in ejection fraction to <50% or >15% decrease from pre-therapy. Univariate and multivariate logistic regression was performed to identify clinical and genomic cardiotoxicity risk factors. SNPs were genotyped and frequency of the major allele (G)/minor allele (A) of the CBR3 and CBR1 genes was calculated. Results: We identified 59 cases of cardiotoxicity after AC and 122 controls. Trastuzumab was associated with cardiotoxicity (univariate/multivariate p=0.015/0.011). Hyperlipidemia (p=0.009), hypertension (p=0.035), and diabetes (p=0.02) were associated with increased risk by univariate analysis. A greater percentage of the major allele (G) of the CBR3 gene was observed in patients with cardiotoxicity than in controls (66% vs 59%, p=0.16, OR=1.39, 95% CI: 0.88-2.21). Conclusions: This is the first study to evaluate SNPs in the CBR pathway as predictors of AC cardiotoxicity in adults. There was a non-statistically significant trend toward increased frequency of the allele G of the CBR3 gene. Further investigation into CBR SNPs in a larger adult sample is needed.
Abstract 14173: Activation of Cellular Immunity in Peripartum Cardiomyopathy: Results of the Multicenter IPAC Registry
Authors: Charles McTiernan, Karen Hanley-Yanez, Jessica E Pisarcik, Penelope A Morel, Leslie T Cooper, Uri Elkayam, James D Fett, Dennis M McNamara
Journal: Circulation (2011)

Introduction: Peripartum Cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Cellular immunity is downregulated during normal pregnancy and reset during the peripartum ...
Patient perceptions about potential side effects and benefits from chemotherapy agents.
Authors: Iryna Kuchuk, Nathaniel Bouganim, Kathy Beusterien, Jessica Grinspan, Lisa Vandermeer, Sasha Mazzarello, Freya Crawly, Stan Z. Gertler, Susan Faye Dent, Xinni Song, Roanne Segal, George Dranitsaris, Mark J. Clemons
Journal: Journal of Clinical Oncology (2013)

6595 Background: Little is known about how breast cancer patients (pts) perceive the relative side effects and benefits of different chemotherapy (CT) agents. The objective of this study was to better understand these preferences in pts receiving CT at a Canadian cancer center. Methods: Pts completed a Web survey. Grade I/II (mild to moderate) and III/IV (moderate to severe) descriptions of 9 common CT side effects were assigned preferences by: conjoint and standard gamble (SG). Conjoint involved making trade-offs among different risks of side effects, yielding preferences (utilities) for each side effect. SG involved choosing to stay in a selected side effect state or taking a gamble between full health (probability p) or being dead (1-p). For each side effect, p was varied until the patient was indifferent of the side effect. Pts were also asked to rate how much of detriment in quality of life they would endure for benefits in survival. Results: 102 women participated, mean age 54 + 11, stage 1 (21%), 2 (24%), 3 (38%) and 4 (18%). Among the grade I/II side effects, a 5% reduction in risk of sensory neuropathy, nausea, and motor neuropathy had the highest impact on preferences. Among grade III/IV side effects, motor neuropathy, nausea/vomiting, and mucositis made the most difference. SG preferences for side effects were lowest (i.e. least preferred) for grade III/IV nausea (0.624) followed by diarrhea (0.633), hand-foot syndrome (0.681), and highest for grade I/II sensory neuropathy (0.757), mucositis (0.756), and myalgia (0.750). Agree/disagree items revealed patients are willing to endure quality of life detriments for improvement in survival; this willingness increased as disease stage increased (p=0.01). Conclusions: Relatively small changes in the risks of some CT side effects may have substantial impacts on pt treatment preferences. Nevertheless, pts will endure significant toxicity for a potential gain in survival. The standard gamble utilities from this population may also be used to quality-adjust life expectancy in cost-effectiveness evaluations of breast cancer chemotherapies.
RECIST measurement through the exhaled breath in lung cancer: Myth or reality?
Authors: Inbar Nardi-Agmon, Manal Abud-Hawa, Ori Liran, Naomi Gai-Mor, Maya Ilouze, Amir Onn, Jair Bar, Rossie Navon, Fred R. Hirsch, Paul A. Bunn, Hossam Haick, Nir Peled
Journal: Journal of Clinical Oncology (2014)

e19023 Background: Exhale breath analysis can assist in early detection of lung cancer (LC). The cancerous cells induce biochemical changes that cause a release of various compounds to blood, some of which are then exhaled at breath as Volatile Organic Compounds (VOCs). We examine whether exhaled breath analysis can be used for monitoring response to systemic therapy in lung cancer patients, as a potential non-invasive tool. Methods: The first breath sample was collected prior to the beginning of first systemic therapy. Repeated samples were collected during treatment period. Computerized tomography (CT) scans were done periodically. Patients' response to treatment was assessed by CT scans, and categorized according to RECIST [RECIST criteria- the Response Evaluation Criteria in Solid Tumors] criteria as: Complete Response (CR), Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD). VOCs profiles were determined by GC-MS [gas-chromatography/mass-spectrometry] and by nanomaterial-based array of sensor. Results: 38 patients with stage III/IV lung cancer were recruited to our study. 33 of the patients had non-small cell lung cancer (NSCLC) and 6 patients had small cell lung cancer (SCLC). 143 breath samples were collected; the number of samples per patients ranges from 2 to 12 samples, with a median of 3 samples. 48 samples were categorized as PR, 36 as SD, and 18 as PD.In order to identify compounds / patterns which distinguish the response categories, comparisons were conducted at 4 levels: baseline samples vs. PR+SD; baseline samples vs. PD; PR vs. SD; PR+SD vs. PD. VOC signature was able to discriminate between disease control and PD by a set of four isolated VOCs in a significant manner. Conclusions: Breath sampling can pose an important tool in clinical practice for the detection of lung cancer, and may serve as a non-invasive biomarker to monitor response to anti-cancer treatment, even before it is indicated by imaging tests. Clinical trial information: NCT01386203.