tbuckley/cabot-search huggingface dataset:
Genetic testing in young women with breast cancer: Results from a web-based survey
Authors: J. A. Shin, S. Gelber, J. Garber, R. Rosenberg, M. Przypyszny, E. Winer, A. Partridge
Journal: Journal of Clinical Oncology (2007)

21093 Background: Young women with breast cancer have an increased risk of harboring a BRCA1/2 mutation. The frequency of genetic testing in this population is not well described. We evaluated the reported frequency and factors associated with genetic testing among young breast cancer survivors identified through the Young Survival Coalition (YSC), an international advocacy group for young women with breast cancer. Methods: Items regarding family history and genetic testing were included in a large web-based survey addressing quality of life and fertility issues for young women with breast cancer. All YSC members were invited by email in March 2003 (N= 1,703 women) to participate in this cross-sectional survey. Results: 657 women completed the on-line survey; 622 were eligible for this analysis (age &lt;40, no metastatic or recurrent disease). Mean age at breast cancer diagnosis was 33 years; mean age when surveyed 35.5 years. Stages included: 0 (10%), I (27%), II (49%), III (12%), missing (3%). 90% of women were white; 64% married; 49% with children; 78% had at least a college education; 42% of women reported a 1 st or 2 nd degree relative with breast or ovarian cancer, and 13% considered themselves high-risk for harboring a genetic mutation at the time of diagnosis. At the time of the survey, 23% of women had undergone genetic testing, and 26% of those tested reported that a mutation was found. In a multivariate model, women who were younger (age 36–40 vs. age =30, O.R. 2.26, p=0.004), more educated (&lt; college vs. &gt; college education, O.R. 2.62, p=0.0009), had a family history of breast or ovarian cancer (O.R. 3.15, p&lt;0.0001), and had had a mastectomy (O.R. 1.99, p=0.001) were more likely to have undergone genetic testing. Non-significant covariates included: age at survey, stage, time since diagnosis, race, marital status, employment, finances, insurance, number of children, comorbidities, baseline anxiety and depression, and fear of recurrence. Conclusion: The majority of women diagnosed with breast cancer age 40 and younger do not undergo genetic testing. Younger, more educated women with a family history of breast or ovarian cancer are more likely to get tested. Further research to define the appropriateness of genetic testing in this relatively high-risk population is warranted. No significant financial relationships to disclose.
Elective surgery targets scrapped in favour of better cancer and A&amp;E services
Authors: Adrian O’Dowd, Gareth Iacobucci
Journal: BMJ (2017)

Targets on waiting times for elective surgery have been abandoned for the foreseeable future, so that the NHS in England can focus on services in most need of improvement, including emergency care and cancer treatment, show new plans. A report from NHS England charts “practical and realistic” steps to improve the NHS over the next two years, including new targets on access to primary care, emergency care, cancer treatment, and growing the workforce.1 The report, which follows on from the NHS Five Year Forward View published in 2014,2 spells out changes that are due to take place across the health service in England, including: #### Box 1: Key improvements planned for general practice
The impact of adjuvant breast cancer (BC) chemotherapy on ovarian reserve and menses.
Authors: Shari Beth Goldfarb, Giuliano Bedoschi, Eli Grunblatt, Sumanta Goswami, Tessa Cigler, Jessica Quistorff, Fernanda Pacheco, Robert Stobezki, Mark E. Robson, Fred Moy, Clifford A. Hudis, Sujata Patil, Maura N. Dickler, Kutluk Oktay
Journal: Journal of Clinical Oncology (2015)

9522 Background: In prior studies, menses was used as a surrogate for fertility. But, anti-mullerian hormone (AMH) may be a better surrogate for ovarian reserve. The goal of this study is to delineate the extent of ovarian damage from specific treatments by using AMH level and menstrual calendars and to determine if chemo-induced amenorrhea and AMH levels correlate. Here we report results from the largest longitudinal study with a pretreatment evaluation to measure the impact of chemo on ovarian reserve in women with BC. Methods: A multi-institutional IRB-approved study was performed in 207 premenopausal women with stage 0-III BC. AMH levels were evaluated at baseline and 1 yr post adjuvant chemo. Menstrual calendars were completed monthly. After the exclusions (failure to f/u, serum sample inadequacy, presumed PCOS, Tam only treatment and consent withdrawal), 104 women ages 26-46 (median 38) were available for analysis at 1 yr post treatment. AMH levels were measured in frozen sera with an ultrasensitive ELISA assay and were log transformed due to non-normal distribution. Results were analyzed with Wilcoxon rank sum test and repeated measures ANOVA to adjust for age, tam use and stage. Results: In the104 evaluable women, 95 pts had HR+ and 21 had triple negative BC. 78 pts received anthracycline-based (ddAC-T/EC-T) chemo and 26 non-anthracycline-based chemo (TC/CMF/TH). In the 104 pts who received chemo,compared to baseline (median0.20ng/ml, 0.001-3.9 ng/ml), AMH levels declined significantly (median 0.12 ng/ml, 0.001-4.47 ng/ml; p < 0.0001) at 1 yr post chemo. The type of chemo, stage and adjuvant tam use post-chemo did not significantly impact the results. Despite a significant decline in ovarian reserve by AMH, 73% (74/102) of women who received chemo and completed menstrual calendars had return of menses by 1 yr post treatment. There was no difference in AMH levels between the women whose menses returned and those who remained amenorrheic. Conclusions: This longitudinal study shows that BC chemo is detrimental to ovarian reserve. The fact that the majority of pts resumed their menses despite a significant decline in their ovarian reserve by AMH indicates that resumption of menses is not a reliable measure of ovarian normalcy/fertility.
Characterizing the costs of complications after cystectomy: Can we target the primary drivers?
Authors: Matthew Mossanen, Ross E Krasnow, Matthew Ingham, Adam S Kibel, Mark A Preston, Steven Lee Chang
Journal: Journal of Clinical Oncology (2017)

304 Background: Radical Cystectomy (RC) is subject to substantial morbidity and patients face complication rates as high as 64% at 90-days. Understanding the costs of complications after RC is essential to improving care. We studied the financial cost of different categories of complications after RC in order to identify drivers of expenditures. Methods: Using the Premier Hospital Database we identified adult patients who underwent RC for bladder cancer from 600 hospitals across the US from 2003-2013. Ninety-day complications were captured using ICD9 codes. Complications were categorized according to Agency for Healthcare Research and Quality Clinical Classification Software. The primary outcome was cost of complication and secondary outcomes were mortality, length of stay (LOS), and discharge disposition. A generalized liner model conforming to a gamma distribution was used to evaluate cost data. Analyses were survey weighted, and all models were adjusted for patient (age, race, obesity, marital status, payer), hospital (bed size, teaching affiliation, rural, region), and surgery characteristics (lymphadenectomy, continent diversion, robotic, operative time, transfusion, surgeon volume, hospital volume) and clustered by hospital. Results: We identified 9,137 RC patients, representing a weighting population of 57,553 patients. The top four most costly complications were venous thromboembolism (VTE $17547), soft tissue ($13523), gastrointestinal (GI $8663), and infectious (non-wound, i.e. sepsis, $7930). Pharmacy related costs were the primary driver of VTE costs. LOS was increased in each complication by 1.7 days for infectious, 4.5 days for soft tissue, 3.5 days for GI, and 3 days for VTE. Being married, having fewer comorbidities, larger hospitals, teaching hospitals, shorter operations, lack of transfusions, high volume hospitals, and high volume surgeons were associated with statistically significantly lower costs of complications after cystectomy. Conclusions: VTE, soft tissue, and GI complications are the most expensive complications after cystectomy, and thereby highlight potential candidates for future quality improvement initiatives.
Phase I dose escalation of the oral histone deacetylase inhibitor (HDACi) resminostat in combination with FOLFIRI in colorectal cancer (CRC) patients: The SHORE trial.
Authors: Henning Schulze-Bergkamen, Dirk Jaeger, Hans-Georg Kopp, Frank Mayer, Michael Bitzer, Anna Mais, Karin Resemann, Bernhard Hauns, Julia Asche, Stefan W. Henning, Bernd Hentsch
Journal: Journal of Clinical Oncology (2013)

3625 Background: Resminostat is a novel oral HDAC inhibitor with broad activity in various cancer models. In CRC models, resminostat revealed synergistic effects with 5-FU and irinotecan/SN-38, indicating its (re-)sensitization potential when applied in combination therapy. Furthermore, resminostat downregulates thymidylate synthase, involved in drug resistance to 5-FU and effectively inhibits HDAC2, one of the target enzymes believed to critically support development of CRC. The phase I/II SHORE trial investigates resminostat in combination with FOLFIRI in patients previously treated with 5-FU. Methods: Patients (pts) with advanced CRC having previously received 5-FU alone or in combination with other agents who were scheduled for FOLFIRI in second or later treatment lines were included. The phase I comprised an open-label, inter-patient, ‘3+3’ dose escalation design with increasing doses of resminostat combined with standard FOLFIRI. Pts received resminostat on 5 consecutive days, followed by a 9-day drug free period (‘5+9’ scheme, i.e. 14-day cycles). On days 3 and 4 of each cycle (C), FOLFIRI was administered. Primary objective of the Phase I part was to determine safety and tolerability, the maximum tolerated dose and pharmacokinetics of the combination. Results: 17 pts (median age 61 yrs; 12 males; 11 ECOG 0; 6 ECOG 1; median therapy line 2 [2-6]) were enrolled in 4 dose levels of resminostat 200, 400, 600 mg QD (3 pts each) and 400 mg BID (6 pts) plus FOLFIRI. Two pts discontinued in C1 and were replaced. No DLT occurred. AEs consisted mainly of GI symptoms of mild and moderate intensity (nausea, vomiting and diarrhea) leading to decreased electrolyte plasma levels in some pts. In the highest dose level tested (400 mg BID) hematological toxicity, mainly neutropenia up to grade 4, was observed leading to dose reductions in 3 pts in C3 and C7. No objective responses were reported, however some pts showed SD for prolonged time (up to 32 w). Results of the completed phase I part will be reported. Conclusions: The combination of resminostat with standard FOLFIRI was safe and well tolerated warranting continuation into the Phase II part of the study. Clinical trial information: NCT01277406.
A phase II trial of zoptarelin doxorubicin in castration- and taxane-resistant prostate cancer.
Authors: Steven Yu, Kanthi Athreya, Stephen V. Liu, Andrew V. Schally, Susan G. Groshen, Denice D Tsao-Wei, David I. Quinn, Tanya B. Dorff, Shigang Xiong, Jacek Pinski, Jurgen Engel
Journal: Journal of Clinical Oncology (2017)

210 Background: Luteinizing hormone-releasing hormone receptors (LHRH-R) are expressed in ~86% of prostate cancers, with sustained expression despite prolonged exposure to LHRH agonists. Limited expression of LHRH-R on normal cells suggests LHRH-R may be a therapeutic target for prostate cancer. Zoptarelin doxorubicin is a cytotoxic hybrid molecule linking doxorubicin to an LHRH analog that selectively targets doxorubicin to cancer cells expressing LHRH-R. Methods: This Phase 2 trial evaluated the clinical benefit of zoptarelin doxorubicin for metastatic castration-resistant prostate cancer (mCRPC) following androgen deprivation therapy and ≥1 taxane-based regimen. The primary endpoint was clinical benefit (CB) defined as progression-free survival (PFS) per RECIST v1.1 at 12 weeks with no dose-limiting toxicities (DLT) or other toxicities resulting in treatment cessation. Secondary endpoints were time to overall progression, response rate, pain response, overall survival (OS), and PSA response. Results: Of 25 patients enrolled, 20 had ≥1 measurable lesion at baseline with PFS ≥12 weeks achieved in 56% and PSA response of PR (4%) and SD (84%). Median PFS and OS were 3.8 and 6.0 months, respectively. Reduced pain was reported by 59%. Treatment was well tolerated, with no cardiotoxicity and neutropenia (all grades) the most common hematologic adverse event. Conclusions: This phase 2 trial demonstrated clinical benefit in 56% of patients with no DLT or other toxicity requiring treatment termination. These results suggest a role for zoptarelin doxorubicin for mCRPC following progression on second- and third-line hormonal therapy. Clinical trial information: NCT01240629. [Table: see text]
<i> Clostridium difficile</i> infection in hospitalized cancer patients.
Authors: Analia Adela Rodriguez Garzotto, Antonio Merida Garcia, Nerea Muñoz Unceta, Maria del Mar Galera Lopez, Maria Angeles Orellana, Susana Cortijo Cascajares, Lara Iglesias, Hernan Cortes-Funes, M. Teresa Agullo Ortuno
Journal: Journal of Clinical Oncology (2014)

e20707 Background: The incidence and severity of Clostridium difficileinfection (CDI) has significantly increased over the past decade. Although the epidemiology and treatment of CDI is well elucidated in the non-oncology population, it is poorly understood among cancer patients. CDI prevention is particularly important for patients with cancer, because diarrhea often results in dose reductions or delays of chemotherapy or radiotherapy. Methods: We performed a retrospective study to assess the incidence and severity of C. difficile infection among adult cancer patients admitted to the Oncology Service at “12 de Octubre” University Hospital, from January 2009 to March 2013. All inpatients with diarrhea underwent testing for the presence of C. difficile (enzyme immunoassay for toxins A and B). Chemotherapy administered, and antibiotics used before the development of CDI symptoms, was noted. Results: Of the 230 admitted patients during the 4-year study period, the overall incidence of CDI was 9.6% (N=22). Of these, 8 (36.4%) and 14 patients (63.6%) were deemed to have mild and moderate CDI, respectively. Patients with CDI (N=5, 22.7%) suffered more severe complications than patients with other enteric infections (N=2, 15.4%). There was a slight trend between previous use of antibiotics and CDI (P= 0.09), however we found no relationship between CDI and previous administration of corticosteroids or proton pump inhibitors. With regards to outcome of chemotherapy, patients with platinum-based therapy were more affected by CDI (N=19, 86.3%), and four of them died. Conclusions: Despite a potential decrease in the incidence of CDI in the last years, this infection still contributes substantially to morbidity and possibly mortality in this vulnerable patient population. There was no relationship between gastrointestinal cancer and CDI. Use of carboplatin chemotherapy was significantly associated with CDI, and CDI was more frequent in gynecologic cancer patients, as these patients are more frequently treated with this therapy. Our study supports the possibility of platinum-based chemotherapy as a risk factor for CDI although the reason for the effect is not clear.
Comparative analysis of DNA-cytometric indices of primary and relapsing ovarian cencer.
Authors: Inna Arnoldovna Novikova, Galina Nerodo, Anna Iurievna Mordan
Journal: Journal of Clinical Oncology (2013)

e16558 Background: A ploidy of an average grade of aneuploidy cells and of proliferation index in ovarian tumor was studied. Methods: 21 patients with ovarian cancer of III-IV grades and 12 patients with acknowledged relapse of the disease aged from 46 to 67 to part in the research. We used CycleTEST PLUS DNA Reagent Kit (Becton Dickinson) for the analysis of DNA in the tumor’s tissues. Preparation of the tumor’s tissues was made with the use of disaggregating device BD Medimachine; after painting with propidium iodide (PI) we analyzed at flow cytofluorimeter BD Facs CantooII. Received data was processed with the help of computer program ModFit LT, allowing to analyze the ploidy and distribution of tumor’s cells according to phases of cellular cycle. Results: There was revealed the 2.5 times predominance of aneuploidy tumors over diploid in case of the relapse of the disease. The DNA index, different from 1.0, was registered in 83.3%, whereas there was noticed 33.3% primary ovarian tumors with aneuploidy content of DNA with predominance of diploidy tumors. There was noticed a tendency to the increase of aneuploidy cells during the relapse of the disease, where they made up 42.7±1.8%, whereas in primary ovarian tumors the share of aneuploidy cells was 40.4±1.6%. The index of proliferation of relapsing tumors was 1.8 times higher than this index of primary tumors, and made up 35.5±2.9 and 26.7±2.1 (p &lt; 0.05). Conclusions: During the relapse of a tumor there is a predominance of aneuploidy tumors over diploid, the index of proliferation is higher in comparison with primary tumors.
Evaluation indel TYMS gene polymorphism in association with response regarding the use of fluoropyrimidines in patients with neoplasms of the gastrointestinal tract in the Brazilian Amazon.
Authors: Danielle Costa, Ney PC Santos, Millene A Bechara, Williams Fernandes Barra, Tayssa CL Vilhena, Mayara FERREIRA Mota, Marianne RODRIGUES Fernades, Eliude RODRIGUES Do Nascimento, Giovanna CHAVES Cavalcante, Paulo PIMENTEL De Assunpcao
Journal: Journal of Clinical Oncology (2014)

e13537 Background: Cancer is a public health problem worldwide, with an estimated of 27 million new cases and 17 million cancer deaths in 2030. In Brazil, estimates for cancer in 2014, indicate the occurrence of approximately 580 000 new cases. Fluoropyrimidines are used in the main chemotherapy regimens targeted to tumors of the gastrointestinal tract. Recently, much has been investigated on causes of different individual responses to chemotherapy.Thus, it has been sought an individualized therapy that can maximize drug efficacy and minimize adverse effects associated with drugs. We aimed to seek the association of an INDEL polymorphism (rs16430) in TYMS gene with the pattern of response to chemotherapy drugs based on fluoropyrimidines, in order to contribute to the development of personalized medicine Methods: We studied 151 samples of cancer patients treated with fluoropyrimidine, from a population of the Brazilian Amazon region with high interethnic admixture. An INDEL polymorphism (rs16430) was genotyped in TYMS gene, that is involved in the response to treatment using fluoropyrimidines. Results: The research reported that most patients had advanced disease at diagnosis, of which 32.7% were treated with palliative intent, and 22.8% neoadjuvant treatment. Our results show that the INDEL polymorphism in the TYMS gene appears to have a protective effect on tumor progression (p = 0.033). Patients treated with fluoropyrimidine who were wild homozygous (INS / INS) had a 24% protection to tumor progression compared to other genotypes of this polymorphism. Estimates of global genetic ancestry of the sample investigated were: 62.4% European, 25.2% Amerindian and 12.4% African. It was possible to establish an inverse correlation between the increase of Amerindian ancestry and metastasis (p = 0.024). Conclusions: Pharmacogenetic studies can provide a personalized therapy toxicity reducing mortality and improving therapeutic efficacy, thereby providing a cancer therapy with better clinical results.
Outcomes of pediatric cancer patients enrolled in phase 1 clinical trials designed for adults: Experience from a major cancer center.
Authors: Vivek Subbiah, Fernando F. Corrales-Medina, Cynthia E. Herzog, Kenneth R. Hess, Daniela Elizabeth Egas Bejar, David S. Hong, Gerald Steven Falchook, Peter Meade Anderson, Cesar Nunez, Winston W. Huh, Aung Naing, Apostolia Maria Tsimberidou, Jennifer J. Wheler, Sarina Anne Piha-Paul, Filip Janku, Eugenie Kleinerman, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2014)

e21024 Background: Phase I trials play a key role in the early evaluation of novel targeted therapies for patients with advanced cancer. Pharmaceutical industry sponsored trials exclude patients less than 18 years of age for phase I clinical trials even in the era of targeted therapy. Some investigator-initiated phase 1 trials combining US FDA approved agents allow patients less than 18 years. We sought to determine the relationship between clinical characteristics and survival outcomes of pediatric patients enrolled in adult-based phase I trials at MD Anderson Cancer Center and to validate the Royal Marsden Hospital (RMH) score and the MD Anderson Cancer Center (MDACC) score as survival predictor tools in this population. Methods: Medical records of 40 patients younger than 18 years who were treated in at least 1 phase I trial at MDACC between 2005-2013 were reviewed. Univariate and multivariate analyses were used to determine which baseline clinicopathologic characteristics were associated with overall survival (OS) and progression-free survival (PFS). Results: The median OS was 8.5 months (95% CI, 5.5-13.2 months). In the multivariate analysis, age ≥15 was the only independent factor that predicted increased OS (P = 0.0065), and >3 prior therapies (P = 0.053) predicted decreased OS. The median PFS duration was 2.8 months (95% CI, 2.3-4.1 months). In multivariate analysis, independent factors that predicted increased PFS were age ≥15 years (P < 0.001) and prior radiation therapy (P = 0.049); ECOG performance status >1 (P < 0.001) and >3 prior therapies (P = 0.002) predicted decreased PFS. RMH score ≥ 2 and MDACC score ≥ 3 were associated with decreased median OS (P = 0.029 and P = 0.031 respectively). Conclusions: It is feasible to include pediatric patients in phase I studies focused on treatment of adults. A composite score using a larger number of pediatric patients needs to be developed using the RMH and MDACC scores in future trials. In the era of targeted therapy more trials should allow earlier evaluation of drug development for pediatric patients.