bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of a supervised exercise program on arm girth measurements in breast cancer survivors.
Authors: Leach Laura M. , Kleski Amy , Spencer Kathy , LaLonde Michelle , Sweeney Thomas J. , Caulin-Glaser Teresa
Published: March 2020

9115

Background: There is minimal research examining the effect of cardiovascular and resistance exercise after surgery and/or radiation treatment to the breast and axillary area. Currently there are no guidelines for activity restrictions; however, medical providers historically have recommended limiting activity of the affected arm in an attempt to prevent the development of lymphedema. This could potentially affect future quality of life and other medical issues in breast cancer survivors. Methods: Female breast cancer survivors (n=79) completed an 8-week group exercise program meeting two days per week for cardiovascular and resistance training. Participants were also encouraged to exercise independently in addition to their group sessions. Bilateral arm girth measurements were performed on all participants upon program entry and exit. Measurements were taken distal to the ulnar styloid process (wrist) and three inches above (upper arm) and below (elbow) the lateral epicondyle of the elbow. All participants included in this analysis attended ≥ 70% of the group exercise sessions and had complete entry and exit measurements. Results: Participants attended an average of 15.94 ± 3.75 exercise sessions during the 8 week program. Changes in arm girth measurement were compared for the surgical side and non-surgical sides of the body using paired t-tests. Arm girth changes in the surgical side of the body were compared to the non-surgical side of the body using the Wilcoxon Ranked Sum test. The surgical and the non-surgical arm girths did not significantly increase at the wrist (p=0.55 and p=0.76), elbow (p=0.31 and p=0.24) or upper arm (p=0.18 and p=0.42). The changes in arm girth observed on the surgical body side were not significantly different from the changes observed on the non-surgical side (wrist (p=0.67), elbow (p=0.44), and upper arm (p=0.36). Conclusions: A structured, group-based exercise program involving both cardiovascular and resistance training did not significantly increase arm girth measurements in breast cancer survivors.
Disease-driven symptoms and response to chemotherapy in treatment-naive patients with advanced non-small cell lung cancer (NSCLC).
Authors: Jones Desiree , Vichaya Elisabeth G. , Wang Xin Shelley , Mendoza Tito R. , Mobley Gary M. , Lu Charles , Cleeland Charles S.
Published: March 2020

9118

Background: The disease-driven symptoms of treatment-naïve patients with advanced NSCLC have not been the primary focus of previous studies. One reason for this gap in the literature is that randomized trials typically lack an opportunity to capture the symptom profiles of patients who are truly treatment-naïve. To address this need, this study sought to: (i) characterize the symptom profile of treatment-naïve patients with advanced NSCLC, and (ii) describe patients’ response to chemotherapy. Methods: The study sampleconsisted of43 treatment-naïve patients (no prior treatment by surgery, radiation, or chemotherapy) with a primary diagnosis of advanced NSCLC from the MD Anderson Cancer Center, and was derived from a larger study (Cleeland et al. J Clin Oncol 29:2859-65, 2011). Patients’ symptoms were assessed pre-chemotherapy, and then prospectively at 6, 12, and 18 weeks from initiation of chemotherapy using the MD Anderson Symptom Inventory Lung Cancer module. Results: The top symptoms reported by patients, in order of severity, were shortness of breath, fatigue, distress, sadness, drowsiness, and pain. Chemotherapy did not significantly improve shortness of breath, drowsiness, pain, disturbed sleep, lack of appetite, coughing, and constipation in this sample of patients, and was associated with a significant increase in levels of fatigue and numbness (mean difference in fatigue at 12 weeks from baseline = 2.8; 95% CI, 0.5–2.9; p = .01; and in numbness from baseline = 1.1; 95% CI, 0.2–2.0; p = .02). Conclusions: This study characterizes the disease-driven symptoms of truly treatment-naïve patients with advanced NSCLC. Knowledge of these symptoms is of intrinsic value in the clinical management of advanced NSCLC as it provides the critical reference point against which symptom palliation must be measured. Patients’ lack of symptomatic improvement from chemotherapy in this study suggests that this sub-set of patients may have had rapidly progressing disease and that chemotherapy may have prevented symptoms levels from worsening. Consistent with literature, transient but significant increase in both fatigue and numbness are chemotherapy-related toxicities.
Using scenarios to explain survival time: Attitudes of people with a cancer experience.
Authors: Stockler Martin R. , Kiely Belinda E. , McCaughan Georgia J. , Christodoulou Sophie , Beale Philip James , Trotman Judith , Grimison Peter , Tattersall Martin HN
Published: March 2020

9126

Background: Most people with advanced cancer want some information on their life expectancy. We sought the attitudes of people with a cancer experience to using three scenarios for survival (best-case, worst-case, and typical) to explain life expectancy to people with advanced cancer. Methods: Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with incurable cancer - providing either three scenarios for survival or just the median survival time. Associations between respondent attitudes and their demographic and tumour characteristics were explored. Results: Characteristics of the505 respondents from outpatient clinics (n=251) and BCNA (n=254) were: median age 58 years; female 74%; completed high school education 80%; breast primary 64%; self-report of cancer spread to other body parts 23% and; a median of 4 years since diagnosis of cancer. More respondents agreed that explaining three scenarios (vs. just the median survival time) would: make sense (93% vs. 75%), be helpful (93% vs. 69%), convey hope (68% vs. 44%), reassure (60% vs. 40%) and help family members (91% vs. 71%); all p-values <0.001. Fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24% v 36%); p<0.001. The proportions of respondents agreeing that each of the 3 scenarios should be presented were: best-case 89%, worst-case 82%, and typical 92%. Most respondents (85%) agreed it would be helpful to receive a printed summary of the scenarios for survival. For information about their own prognosis, 88% preferred all three scenarios and 5% a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95% v 90%, p=0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31% v 13%, p<0.001). Conclusions: Most respondents judged presentation of best-case, worst-case and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.
Relapse-specific mutations in cytosolic 5’-nucleotidase II in childhood acute lymphoblastic leukemia.
Authors: Meyer Julia , Wang Jinhua , Hogan Laura E. , Patel Jay , Tang Zuojian , Zumbo Paul , Li Sheng , Zavadil Jiri , Levine Ross L. , Cardozo Timothy , Hunger Stephen , Raetz Elizabeth A. , Morrison Debra J. , Mason Christopher , Carroll William L.
Published: March 2020

9507

Background: Relapsed childhood acute lymphoblastic leukemia (ALL) carries a very poor prognosis despite intensive retreatment that often includes allogeneic stem cell transplantation, due to intrinsic drug resistance. Novel therapeutic approaches are urgently needed and identification of the biological pathways that mediate resistance might provide targets for the effective prevention and treatment of relapsed ALL. However, the spectrum of somatic mutations responsible for ALL relapse is not yet known. Methods: We profiled the transcriptome of matched diagnosis and relapse bone marrow specimens from 10 pediatric B lymphoblastic leukemia patients using massively parallel sequencing technology (RNA-seq) to identify novel mutations specific at disease recurrence. Results: Transcriptome sequencing identified 20 newly acquired novel non-synonymous mutations in 10 relapse specimens not present at initial diagnosis. Two patients harbored relapsed specific mutations in the same gene, NT5C2, which codes for the Cytosolic 5’-nucleotidase II protein at different sites in the protein sequence. Mutations were validated as relapse specific after Sanger resequencing of germline, diagnosis and relapse DNA. RNA-seq coverage of each mutation was >100X, indicating that if a relapsed clone were present at diagnosis it made up < 1% of the bulk leukemia. Full exon sequencing of NT5C2 was completed in 61 additional relapse specimens, identifying 5 additional mutations which were also confirmed as relapse specific. Structural modeling of the relapse-associated mutations in the encoded protein Cytosolic 5’-nucleotidase II suggests alteration of enzyme subunit association/dissociation. Clinically, patients who harbored NT5C2 mutations were more likely to relapse earlier following initial diagnosis than those patients without mutations (p=0.03). Conclusions: Mutations in NT5C2 are associated with the outgrowth of drug resistant cells in childhood ALL.
Results of autologous transplants for children from a tertiary cancer center in India.
Authors: Dongre Amol , Singh Randeep , Thippeswamy Ravi Shankar , Goyal Gautam , Kannan Sadhna , Bagal Bhausaheb Pandurang , Gawande Jayant Shankar , Kurkure Purna Arun , Banavali Shripad , Khattry Navin
Published: March 2020

9559

Background: Autologous transplantation is a curative option for children with various malignancies. We report the results of our center with the aim of evaluating toxicities and prognostic factors that may influence decision making to use our limited resources judiciously. Methods: Forty-six patients diagnosed below 18 years from 1st April 1994- 28th February 2011 were included in this retrospective study. Twenty-four patients had lymphoma, 12- neuroblastoma and 10-others ( 5- acute leukemia, 4- Ewing sarcoma and 1 - rhabdomyosarcoma). Twenty-eight patients received peripheral blood stem cells, 12 – marrow and 6-both. Prognostic factors evaluated for overall survival (OS) and progression-free survival (PFS) were remission status at transplant, baseline and pre-transplant serum albumin, time interval between diagnosis and transplant, type of malignancy and number of lines of chemotherapy pre transplant. Results: Median age at diagnosis and transplant were 9 and 12 years respectively. Median baseline and pre transplant serum albumin were 3.6 and 3.9 g/dl. Median number of lines of chemotherapy was 2. Median time from diagnosis to transplant was 1.1 years. Incidence of grade 3 and 4 oral mucositis and diarrhea were 46% and 25% respectively. At the time of transplant, 45% were in complete remission (CR), 41% in partial remission (PR) and 13% in refractory state. Total Parenteral Nutrition (TPN) was used in 63% patients with median duration of 11 days. No patient developed sinusoidal obstruction syndrome.Median days to neutrophil and platelet engraftment were 11 and 15 days respectively. Neutropenic sepsis leading to death was seen in 17%. Median follow up was 1.5 years. At 2 years, the probability of OS and PFS were 39% and 35% for all patients while OS and PFS for lymphoma, neuroblastoma and others were 45% and 32%, 17% and 0% and 50% and 40% respectively. CR at transplant was the most important determinant of better OS (59 % vs 28%; p = 0.000004) and PFS (53% vs 8%; p = 0.0000018). Conclusions: CR at transplant is the most important prognostic factor. Patients with neuroblastoma have dismal outcome which requires reevaluation of transplant strategies for this group.
Use of pharmacokinetic modeling to optimize direct inhibition of the "undruggable" target EWS-FLI1 of Ewing sarcoma.
Authors: Toretsky Jeffrey , Hong S. Peter , Gamble S. Ellen , Hong Sung-Hyeok , Kobs Christina L. , Elsass Karen E. , South Natalie L. , Summer Stephen J. , Monroe Philip J. , Uren Aykut
Published: March 2020

9575

Background: Chimeric transcription factors are ideal anti-cancer targets; however, they lack enzymatic activity thus rendering them ‘undruggable’ proteins. The EWS-FLI1 fusion protein of Ewing sarcoma (ES) has been validated as an anticancer target both alone and as a partner of RNA Helicase A (RHA). Our prior work identified the small molecule YK-4-279 as a specific inhibitor that blocks RHA from binding to EWS-FLI1. Blocking this interaction leads to apoptosis. We have modeled YK-4-279 treatment using ES cells to establish the duration of YK-4-279 exposure that leads to apoptosis. Methods: Apoptosis was measured by caspase-3 cleavage. A validated plasma detection method allows for HPLC measurement of YK-4-279. Pharmacokinetic (PK) models of YK-4-279 for both intraperitoneal (IP) and intravenous (IV) administration were developed in SD rats and BL6 mice. Results: ES cell lines were exposed to YK-4-279 over a time-course, followed by a caspase-3 activity assay that demonstrated a minimum of 16 hours exposure was necessary to achieve maximal apoptosis using either 3 or 10 microM compound. A dose-dependency assay demonstrated that while apoptosis could be achieved with 30 – 80 microM YK-4-279 after 4 hours of treatment, caspase-3 activity was less than or equal to 3 microM for 16 hours. Rat PK modeling demonstrated a t1/2 of 30 minutes following IV administration. BL6 mice demonstrated similar kinetics to the rat. SCID/bg mice, which are necessary for tumor efficacy studies, demonstrated approximately 50% faster clearance than either rat or BL6 mice. Absolute bioavailability for IP administration was 41%. Conclusions: Models will be created to optimize IP dosing regimen. The optimized IP dosage and dosing intervals will be evaluated in tumor bearing animals in order to advance development of YK-4-279. The results of these studies will be used to guide toxicology studies in animals. In addition, pharmacodynamics models are being developed to compare YK-4-279 levels with functional activity. The combined results of these investigations will lead to human clinical trials for this first-in-chemical class, first-in-mechanism drug candidate.
Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: Results of a randomized phase III intergroup study (TML study).
Authors: Arnold Dirk , Andre Thierry , Bennouna Jaafar , Sastre Javier , Osterlund Pia J. , Greil Richard , Van Cutsem Eric , Von Moos Roger , Reyes-Rivera Irmarie , Bendahmane Belguendouz , Kubicka Stefan
Published: March 2020

CRA3503

The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Neoadjuvant chemotherapy in locally advanced breast cancer.
Authors: Soraya Sami sahnoun
Published: March 2020

e11034

Background: Neoadjuvant chemotherapy(NAC)is one of the treatment options for locally advanced breast cancer. In this study, we evaluated the efficacy and safety of 4 cycles of NAC doxorubicine,docetaxel and cyclophosphamide(TAC),correlation between the response to NAC and molecular classification sub-groups and between the pCR and the time to progression(TTP). Methods: This is a prospective study from January 2005 to December 2008.110 pts with locally advanced breast cancer stage III.All pts have received 4 cycles of NAC based on docetaxel 75 mg/m², doxorubicine 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks, followed by surgery.101 pts were assessed, since 9 of them have progressed on treatment and came out of the study. Pts were stratified according to age, menopausal status, histopathological analysis (luminal tumors(ER-positive and HER2-negative), triple-negative tumors (TN)and HER2-positive tumors), response to the treatment and survival. The median follow up of patients was 39 months. The statistical study was done using SPSS 17. Results: The median age was 41(23–65).30% of pts were younger than 35 and 80% were premenopausal. 55% luminal tumors(56 pts), 33% HER2 positive(33 pts) and 12 % TN(12 pts).CRR was estimated at 89%(37% of CR and 63% of PR).There were 23, 7% of pCR according to Chevallier’s classification. In luminal, TN and HER2-positive pCR rates were 16%(9 of 56), 66,6%(8 of 12), and 21,2%(7 of 33) respectively. Multivariate analysis showed that the ER status was the only significant predictor of pCR(P = 0.025).HER2 status was not significantly associated with pCR(P= 0,423).TTP was 50 months. In luminal tumors, TN and HER2-positive tumors the TTP was respectively 59, 52 and 49 months. There was not a significant difference in TTP between the pCR(51 months) and the non-pCR group(44 months)(CI 95, p= 0.109).Grade III/IV toxicity included neutropenia(22%), febrile neutropenia(6,5%), mucositis(13%), and diarrhea(4%). Conclusions: Breast cancer occurs in young women in Algeria. In this study, neoadjuvant TAC was effective and well tolerated. The ER status was the only significant predictor of pCR. The molecular classification group with the highest percentage of pCR was the TN group. pCR was not associated with a better prognosis.
Invasive ductal breast cancer, tumor size, and its correlation between physical examination, imaging techniques, and pathological anatomy.
Authors: Lopez-Gonzalez Ana , Ibeas Patricia , Carmona Maria Soledad , Rivero Elisabeth , Lopez Roberto , Huelves Miriam , Doger de Speville Bernard Gaston , Cantos Blanca , Pastrana Miguel Angel , Provencio Mariano
Published: March 2020

e11035

Background: The most frequent indication of magnetic resonance in breast cancer is the evaluation of tumoral extension. Several studies suggest that mammography and ultrasound underestimate tumor size. We try to analize the correlation between the tumor size of invasive ductal carcinomas in physical examination, mammography, magnetic resonance and pathological anatomy. Methods: We review the 290 magnetic resonance made in our Radiology Department from 1st January 2009 to 1st September 2010. 56 of them were applied as complementary study before surgery of suspected lesions of breast cancer. We made an analysis of paired test, and then a hypothesis test for equal sample testing, supported by an analysis of power curves. The paired test analysed were physical examination (PE)- mammography - magnetic resonance (MR) - pathological anatomy (PA). Results: A 100% were women; average of age of 54.1 years old. A 42.8% were premenopausal. Averages of tumor size: 18.3mm in PE; 18.8mm in mammography; 25.3mm in MR and 24.8mm in PA. The correlation between the tumor size in PE and PA is not statistically significant (p=0.05, 95% CI 11.07; 1.93), and also between the mammography and the PA (p=0.05, 95% CI 10.69; 1.47). The correlation between tumor size in mammography and MR is statistically significant (p=0.05, 95% CI -9.83; -3.26), and also between MR and PA (p=0.05, 95% CI -3.31; 4.25). We analysed the relation between clinical tumor size by MR and PA size, and in a 25% of the cases, the clinical and the pathological stage were different. The pathological was more advance in a 57.1% of them. Conclusions: Mammography underestimate the tumor size, with no correlation with the pathological tumor size. However, there is a good correlation between the tumor size in MR and the pathological size. The MR is the most reliable imaging technique to optimize the surgical and oncological treatment in patients with breast cancer.
Role of clinical and histologic factors in decision making on adjuvant therapy of small HER2-positive breast cancer.
Authors: Azam Faisal , Yousif Saif , Aaseem Aarifah , Ahmed Eliyaz
Published: March 2020

e11053

Background: With increased use of screening mammography for breast cancer (BC), the incidence of small (T1a, b), node negative BC has increased. These cancers are considered low-risk and hence not offered adjuvant (adj) chemotherapy (CT). However, increasing retrospective studies suggest that outcomes in small node negative HER-2 positive BC might be worse than the HER-2 negative tumours of similar size. Current guidelines generally do not recommend adj CT and Trastuzumab (T) for small (T1 a, b) HER-2 positive tumours. As a part of our ongoing audit on the outcome of small HER -2 positive BC, we wished to determine the factors that oncologists consider in decision making on adj treatment of these tumours in the absence of clear guidelines. Methods: Patients (pts) with a diagnosis of node negative T1a, b, HER-2 positive BC treated across our cancer network, between Jan 2008 and Dec 2011, were identified from our electronic database. Results: A total 230 pts had stage T1, HER 2 +ve BC. Out of those 41(17%) pts had tumour size of < 1cm (13, 31%pts were T1a and 28, 74%pts wereT1b) and node negative disease. Median age was 55 years (29-84yrs). 33 Pts had BCS and 8 pts had mastectomy. All pts with BCS received adj radiotherapy and all pts who were ER positive received adj endocrine therapy. 21(51%) out of 41pts received adjuvant CT and T. All pts had anthracycline based CT. The clinical and pathological characteristics of pts who received adj CT and T were as follows; Median age- 50 (33-64years), grade 1- 1(4%), grade 2 – 9(43%), grade 3- 11(53%), LVI present- 2(9%), LVI absent- 7(34%), LVI unknown – 12(57%), ER positive- 16(76%), ER negative – 5(24%). None of the pts had recurred or died at the time of analysis of the data and longer follow up is needed for survival analysis. Conclusions: In the absence of clear guidelines on adj CT and T in node negative small HER-2 positive BC, the oncologists relied on the traditional factors such as grade, ER status in risk stratification and decision on adj therapy. Tumour grade was the most important factor but age and ER status were not discriminating factors in this study. Prospective randomised trials needed to clearly define the role of adj systemic therapy in this group of pts.
Phase II study of lapatinib and tegafur combination efficacy for the treatment of HER2+ metastatic breast cancer.
Authors: Manikhas Alexey , Sharvashidze Ineza O. , Kotkova Tatjana N.
Published: March 2020

e11086

Background: One of effective ways to overcome resistance to trastusumab is to prescribe lapatinib, an inhibitor of ErbB1 and ErbB2 receptors, in combination with capecitabine, a fluopirimidine cytostatic agent. We examined the efficacy and safety of combination of lapatinib plus tegafur, another oral fluopirimidine, in patients with ErbB2-positive metastatic breast cancer (MBC). Methods: 13 patients with HER2+ MBC were enrolled into the study. 11 patients were analyzed, as 2 women had been included into the study too late to be assessed. Median age was 43.5 years. All patients had previously received trastuzumab for MBC, 92% of patients had been treated with taxanes, 77% - with anthracyclines, and 31% received capecitabine. 69% of patients were treated with more than 2 lines of chemotherapy for MBC. The study included 4 patients with CNS metastases. During the study, the patients received lapatinib 1250 mg/day and tegafur 1200 mg/day, days 1-21, with 3-week intervals. Results: 1 patient achieved and still is in partial response which has been lasting for 5 months, while disease stabilization was observed in 9 out of 10 cases. The clinical benefit rate in this trial was 90%. There was 1 case of the disease progression. At the time of analysis median TTP was 10.1 months (95%CI 6-13). The combination of lapatinib and tegafur was effective in 4 out of 5 patients with CNS metastases. There were no adverse events greater than grade I observed on lapatinib plus tegafur therapy. Diarrhea was the most common adverse event, but it did not compromise the patients' quality of life. Conclusions: The lapatinib plus tegafur combination is a promising option for treatment of patients with HER2+ MBC after progression on trastuzumab-containing therapy. This mode was acceptable for patients who had received 2 or more lines of previous therapy. The combination was well tolerated by the patients. Both agents being oral formulations, the treatment mode is quite suitable for outpatient use.
A randomized, open-label, phase II study of lapatinib / capecitabine, lapatinib / vinorelbine, or lapatinib / gemcitabine in patients with ErbB2-amplified metastatic breast cancer progressing after taxane treatment: Results of an interim analysis (GLICO-0801 / EGF111792).
Authors: Gomez Henry Leonidas , Neciosup Silvia P. , Tosello Celia , Xavier Patricia , Neron do Nascimento Yeni , Fanelli Marcelo , Ismael Gustavo , Bines Jose , Sampaio Carlos , Lerzo Guillermo Luis , Capo Adolfo Miguel , Mano Max S. , Fein Luis , Werutsky Gustavo , Barrios Carlos H.
Published: March 2020

e11087

Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.
Breast cancer screening guidelines: Is it time to revisit? A survey.
Authors: Rao Archana C. , Gopaluni Srivalli , Lemke Sheila M.
Published: March 2020

e11089

Background: Breast cancer is the most common non-skin cancer among women in US. In a 2012 report by CDCbreast cancer screening rates are falling short of government targets. At least 10 different societies have laid out screening guidelines, making it difficult to follow. We conducted a survey to better understand adherence to guidelines among health care providers. Methods: A questionnaire comprising of 15 questions was distributed to 120 providers within the Department of Medicine at a University Hospital. Results: 68% returned completed questionnaires: Residents (53%), Attendings/Fellows (36%) and Nurse Practioners/Medical students (11%). Despite 60% respondents claiming that screening guidelines were easy to comprehend and follow; the table suggests otherwise. 49% of the respondents follow United States Preventive Services Task Force guidelines (USPSTF) 28% of these commenced screening at age 40; against the recommendations to start at age 50 and to initiate discussions between the ages of 40-50. 16% of the respondents followed National Comprehensive Cancer Network (NCCN)/American Cancer Society guidelines. 46% of these commenced screening at age 50 or between ages 40-50 contrary to recommendations to begin screening at age 40. Similarly 42% of respondents chose to discontinue screening at the age of 75 in concordance to USPSTF guidelines. 5% chose to screen indefinitely and 1% said they would individualize. 52% did not conform to any guidelines. 69% advocated self breast examinations despite most societies not encouraging the same. Conclusions: While majority of providers follow USPSTF guidelines, there is a considerable discordance between guidelines respondents claim to follow and their practices. This could be attributed to the lack of uniformity in the guidelines across various societies making it harder to comprehend and recall. A unifying consensus would make it easier for providers to improve effective screening. [Table: see text]
Image-guided biopsy of non-palpable breast lesions: Experience of a university hospital in Mexico City.
Authors: Morales-Espinosa Daniela , Navarro-Garcia Lilian Monica , Green Dan , Motola Daniel , Alvarado-luna Gabriela , Cortes-Gonzalez Ruben
Published: March 2020

e11098

Background: Breast cancer is the most common cancer in women in Mexico. It is mostly diagnosed at advanced stages. Objective: To describe the experience of image-guided biopsies of non-palpable breast tumors in a University Hospital in Mexico City. Methods: Medical records from the Radiology and Oncology Department (January 2007 - April 2011) were reviewed. Patients with incomplete medical records as well as those lacking imaging control and pathology report were excluded. Results: A total of 123 medical records were obtained,12 were excluded. The median age was 50 years (rank 21-88). Most patients were asymptomatic. Medical indications leading to biopsy: see table below. Of the studied population, 56% had a family history of any type of cancer; 40% had a family history of breast cancer. Nine patients had a past medical history positive for breast cancer, 8 patients had a past medical history of any type of cancer. 26 patients were nulligravid and 60 post-menopausal; of which 27 had received hormone replacement therapy. 24 patients had positive contraceptive use. Most patients were catalogued as BIRADs 4A. From all the imaged-marked lesions, only 18 were malignant; 72% of which were carcinoma in situ. Most procedures were ambulatory; only 15 patients had to be admitted. The complications rate was very low (6%), 1 procedure-related infection, 3 seromas and 3 hematomas. Conclusions: Imaging-guided biopsies are a safe, with very low morbidity, accessible procedure. It helps to prompt effective treatment; especially in patients with non-palpable lesions who would otherwise not be diagnosed until advanced stages. [Table: see text]
Feasibility, efficacy, and cosmetic effect of three-dimensional conformal external beam partial breast irradiation for the selected early-stage breast cancer patients after breast-conserving surgery in China.
Authors: Xu Min , Li Jianbin
Published: March 2020

e11520

Background: To explore the feasibility, efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation after breast-conserving surgery for the selected Chinese early stage breast cancer patients Methods: Forty four early stage breast cancer patients undertaken EB-PBI after breast-conserving surgery. Twenty patients undertaken CT simulation scan in the state of moderate deep inspiration breathing hold (mDIBH), and twenty-four patients during free breathing (FB). The surgical cavity marked by silver clips was delineated and defined as gross tumor volume (GTV), and planning target volume (PTV) was defined as the area encompassed GTV with extended margin of 15 mm for the patients treated in the state of mDIBH or 20 mm for the patients treated in the state of FB. EB-PBI was planned and carried out by three-dimensional conformal radiotherapy (3DCRT) , the total prescribed dosage was 34 Gy delivered in 3.4 Gy per fractions in thirty nine patients and 38.5Gy delivered in 3.85 Gy per fractions in five patients, twice per day at intervals of at least six hours, in five consecutive days Results: Grade 1 of acute radiation-induced dermatitis was observed in 38.6% (17/44) of all the patients, no equal or more than grade 2 of radiation-induced dermatitis was observed, and no any grade of acute radiation-induced pneumonitis was observed. Cosmesis scored basing on Harris critieria was good or excellent in all cases at the time of six months after radiotherapy and in 94.9% cases at the time of two years after radiotherapy. The 2-, 3- and 5-year local control rates were 100% (39/39), 98.8% (30/31) and 93.8% (15/16), respectively. The 2-, 3-, and 5-year survival rates were all 100% and no metastases occurred Conclusions: EB-PBI delivered by 3DCRT is feasible for the selected Chinese early stage breast cancer patients after breast-conserving surgery, satisfactory cosmetic effect, local control rate and long-term survival rate are obtained, meanwhile, acute radiation response rate is lower.
Cost-effectiveness analysis of neoadjuvant chemotherapy with intensive dose of epirubicin and different cycles in patients with locally advanced breast cancer: 4 FE100C versus 6 FE100C.
Authors: Ramirez Nicolas , Herrera Jorge Eduardo , Chavez Jose Fortino , Astudillo Horacio
Published: March 2020

e11565

Background: There are different combinations of neoadjuvant chemotherapy (NCT) to treat locally advanced breast cancer (LABC); treatment with cytostatics drugs make it a costly concern, by establishing economic differences in the consumption of healthcare resources. To compare the cost-effectiveness of two NCT strategies (4FE100C vs. 6FE100C). Methods: It was made a cost-effectiveness analysis (CEA) of two treatment schemes (4FE100C vs. 6FE100C) in patients with clinical stage III breast cancer, each cohort included 48 patients. Effectiveness parameter: pathologic complete response (pCR). Differential cost: incremental cost-effectiveness ratio (ICER) using a Markov’s model. Results are expressed in terms of incremental cost per extra unit of effectiveness. Costs were expressed in Mexican (MXN) pesos ($) as of 2005; these were calculated under the perspective of public healthcare system (SSP, for its acronym in Spanish) denominated IMSS, with a 3 to 4 years analytical horizon. In order to determine the robustness of the results, a sensitivity analysis was carried out by modifying only the medical direct costs with a 3% discount rate. Results: The use of 6FE100C offered greater effectiveness compared against 4FE100C; the medical direct cost of only the cytostatic drugs for NCT with 6 FE100C and 4 E100C generated a cost per case of $30,467.00 MXN (€ 2,343.61) and $18,004.00 MXN (€ 1,384.92), respectively. The greatest unit price was given by epirubicin. The CEA demonstrated that the cost-effectiveness (C/E) was greater with 6 FE100C and the incremental cost-effectiveness ratio (ICER) showed that it was necessary to pay $11,765,925.42 MXN (€ 905,071.20) because it tells us how much it is paid additionally for every extra unit of effectiveness (pCR) which assumes 6 FE100C in front of 4 FE100C. The sensitivity analysis performed shows the robustness of the results. Conclusions: The6 FE100C scheme is the chemotherapeutic strategy with better cost-effectiveness ratio and is the most efficient in the short run for treating LABC.
The predictive value of protein, glucose, and lactate for a diagnosis of neoplastic meningitis.
Authors: McClain Jonathan , Glantz Michael J.
Published: March 2020

e12005

Background: Neoplastic Meningitis (NM) is a complication of many common cancers that occurs with an incidence as high as 15% in some cancer types. Diagnosis remains elusive with poor screening tools and insensitive diagnostic options. Methods: A retrospective analysis of 341 consecutive patients with suspected NM was undertaken. Clinical presentation, demographic, cytologic and MRI data were recorded. Using cytology as the diagnostic gold standard, sensitivity, specificity, ROC curves and likelihood ratios were calculated. Results: 210 patients met inclusion criteria, 87 with primary brain tumors (PBT), 72 with non-CNS solid tumors, and 44 with lymphomas. 111 patients were male; 123 (58.6%) ultimately had a positive cytology. Only 59% of patients with positive cytology presented with symptoms concerning for NM. 32.9% of patients with PBTs and positive CSF cytology exhibited neurologic symptoms suggestive of NM. Patients with non-CNS solid tumors and positive CSF cytology presented with symptoms concerning for NM 80% of the time. Patients with cytology-positive, MRI-positive and symptom-positive NM had very different survivals. Potentially informative CSF values are in table below. Conclusions: A definitive diagnosis for patients with suspected NM remains elusive without a positive cytology, but some clinical, radiographic, and CSF findings are useful for raising diagnostic concern, and for screening in at-risk populations. Symptom-positive or MRI-positive NM may represent different diseases than cytology-positive NM. [Table: see text]
Gene polymorphisms of folate metabolizing enzymes and susceptibility to lung adenocarcinoma in Serbia.
Authors: Jankovic Radmila , Cavic Milena , Krivokuca Ana , Jakovljevic Ksenija , Malisic Emina , Spasic Jelena , Radosavljevic Davorin , Radulovic Sinisa
Published: March 2020

e12020

Background: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are important enzymes of the folate metabolism and are suggested as new prognostic factors for lung cancer. Cytosine to thymine transition at nucleotide 677 (C677T) leads to reduced MTHFR activity. The TS promoter has a tandem repeat polymorphism (2R, 3R) and a guanine to cytosine transition in the 3R allele related to TS protein expression. The aim of this study was to analyze the association of MTHFR and TS polymorphisms with lung adenocarcinoma in Serbia. Methods: A case-control study including 55 late-stage lung adenocarcinoma patients and 53 healthy subjects was performed. Restriction fragment length polymorphism analysis was used for MTHFR and TS genotyping. Depending on the presence of high (3RG) or low (2R, 3RC) expression alleles, TS functional groups were subclassified into HH (3RG/3RG), HL (2R/3RG, 3RG/3RC) and LL (2R/2R, 2R/3RC, 3RC/3RC) groups. Descriptive analyses included genotype and allelic frequencies; the odds ratio (OR) and 95 % confidence interval (CI) were calculated as an estimate of relative risk. Significance was considered for p < 0.05. Results: The distribution of the MTHFR variants in patients vs. controls was 61.8 % vs. 24.5 % for CC, 32.7 % vs. 62.3 % for CT and 5.5 % vs. 13.2 % for TT. A significant difference in CC vs. TT+CT MTHFR genotype distribution was observed between patients and controls (χ2 = 13.79; OR = 4.98; 95 % CI, 2.14 – 11.61). There was no significant association between the TS polymorphisms and the risk of lung adenocarcinoma occurrence, but in the CT+TT MTHFR subgroup, a nonsignificant difference in LL vs. HL+HH TS genotype distribution was observed between patients and controls (χ2 = 0.04; OR = 1.07; 95% CI, 0.31 – 3.67). Conclusions: A significant corelation between the CC MTHFR genotype and lung adenocarcinoma occurence in Serbia was found. Also, there was no significant correlation with lung adenocarcinoma occurence in the CT+TT MTHFR subgroup for carriers of the LL TS genotype. As this study was performed on a relatively small sample size further large case-control studies including analysis of gene-gene interactions with genes coding for other folate metabolism enzymes is needed.
Investigating parent of origin effects (POE) and anticipation in Irish Lynch Syndrome kindreds.
Authors: Farrell Michael P. , Hughes David J. , Schmid Jasmin , Boonstra Philip S , Mukherjee Bhramar , Walshe Margaret B. , Mac Mathuna Padraic M. , Gallagher David J
Published: March 2020

e12031

Background: Genetic diseases associated with dynamic mutations often display parent-of-origin effects (POEs) in which the risk of disease depends on the sex of the parent from whom the disease allele was inherited. Genetic anticipation describes the progressively earlier onset and increased severity of disease in successive generations of a family. We sought evidence for a specific POE effect in Lynch syndrome families by studying the ages at diagnosis in the offspring of affected parent-child pairs. In addition, a paired t-test and a specifically developed bivariate statistical approach were used to assess a possible role of anticipation. Methods: Affected parent-child pairs (APCPs) (N = 53) were evaluated from kindreds (N = 20) with known germline MMR mutations. Differences in the mean age of LS associated cancer diagnosis were compared between various groups via t-tests: all p-values were 2-sided. Different group comparisons include: (1) unique parental ages (mothers vs. fathers) (2) affected offspring ages (mothers vs. fathers (3) age of affected female offspring (mothers vs. fathers (4) age of affected male offspring (mothers vs. fathers. Results: There were no statistically significant differences in diagnosis of offspring or parents. Sons of affected mothers were more likely to be affected than daughters of affected mothers. However, the affected cohort/study number is small and while affected sons of affected mothers were diagnosed with cancer almost 3 years younger than female offspring (39.7 vs 42.5), this finding failed to reach clinical significance. Comparison in age at diagnosis in 53 affected parent-child pairs with Lynch syndrome associated malignancies Conclusions: These data demonstrate a similar age at diagnosis among all offspring of affected mothers that was indistinguishable from affected fathers. This study will be expanded to recruit more eligible affected parent child pairs to increase the power of this evaluation. The Veiland & Huang algorithm will be used to compare mean ages of affected parents and children.
Using primary patient data to identify the symptoms of brain metastases to develop a patient-reported outcome measure.
Authors: Lasch Kathryn Eilene , Fitzgerald Kristina , Ganguli Arijit , Bonthapally Vijayveer , Pompilus Farrah , Delbecque Laure , Ray Saurabh
Published: March 2020

e12515

Background: Increasingly, there has been a public call for direct patient input into the development of patient reported outcome (PRO) measures of treatment benefit in adult oncology clinical trials. Patient involvement is especially important in conditions where there is poor prognosis and comparative treatment benefit is minimal with standard outcome measures such as overall or progression free survival. To develop a PRO instrument specifically for patients with brain metastases (BM), this study interviewed patients in this population and also reviewed the clinical literature to identify the signs and symptoms relevant to BM. Methods: A literature search was performed inMEDLINE for articles published between 2000 and 2010. Individual in-depth interviews were conducted with 19 patients with BM using open-ended questions to elicit the most frequent and the most bothersome symptoms. Patient inclusion criteria included a diagnosis of BM and being eligible for whole brain radiotherapy. Results: The literature review identified the following symptoms as important: intracranial pressure symptoms (e.g., headache, nausea, vomiting), seizures, and focal neurological symptoms (e.g., paralysis, mental status changes, memory, motor loss/weakness, visual loss/changes). The most frequent symptoms reported by patients in the interviews were: headache (74%), memory loss (63%), vision problems (58%), loss of balance (53%), and physical weakness (53%). Also, the patient interviews identified the following as most bothersome: headache (32%) and vision problems (21%). The patients reported additional concepts not identified in the literature review, including pain, fear, falling, fainting, and difficulty reading. Some symptoms or signs identified in the literature were not mentioned by patients during the interviews such as intracranial hypertension and hemorrhage. Conclusions: Although there was considerable overlap among patient and literature reports, including patient input broadened the comprehensiveness of potential symptoms. The results suggest the added value of collecting direct, primary patient data when developing measures to assess benefits of treatment in BM patients.
Doxorubicin-induced vascular toxicity: Targeting potential pathways to reduce procoagulant activity.
Authors: Bar-Joseph Hadas , Ben-Aharon Irit , Tzabari Moran , Savion Naftaly , Shalgi Ruth , Stemmer Salomon M.
Published: March 2020

e13080

Background: In a former study in mice using the gonads as an end-organ prototype, we have characterized by real-time intravital imaging an acute deleterious effect of doxorubicin (DXR) on the gonadal vasculature, manifested by a reduction in blood flow and disintegration of the vessel wall. We hypothesized this pattern may represent the formation of microthrombi. We aimed to further characterize the effect of DXR on platelets’ function and to use potentially protectants to reduce DXR acute effect on the blood flow. Methods: 100 µg/mouse 24 hours and 1 hour prior to DXR treatment (8 mg/kg), or with eptifibatide (integrilin,75µg/mouse) 90min prior to DXR treatment. Testicular arterial blood flow was examined in real-time by pulse wave Doppler ultrasound. Platelet adhesion to confluent endothelial cells (EC) was evaluated following exposure of EC to DXR (100 µM) for 4h followed by exposure to whole blood under defined shear rates. Fixed platelets were immunostained by anti- CD41a antibody. DXR effect on platelet adhesion was determined by pre-incubation of platelet rich plasma for 15min with increasing concentrations of DXR and induction of aggregation by ADP. For in vivo study, mice were injected with either LMWH (Enoxaparin; Clexane). Results: There was a significant 3.6-fold increase in platelet adhesion to DXR-exposed EC (p<0.002) reflecting the toxic effect of DXR on EC. Yet, significant DXR- dose dependent decrease in platelet aggregation was observed reaching up to 40% inhibition at 100 µM (p<0.001). Testicular arterial blood flow was preserved as a result of pre-treatment with LMWH or eptifibatide prior to DXR (P<0.01). Conclusions: DXR-induced acute vascular toxicity may trigger the coagulation pathway while enhancing platelet adhesion yet inhibiting massive aggregation, which result in compromised blood flow due to microthrombi formation. Anti-platelet/anti-coagulant agents appear to be effective in reducing the detrimental effect of DXR on the vasculature.