bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormetic Effects of Early Juvenile Radiation Exposure on Adult Reproduction and Offspring Performance in the Cricket (Acheta domesticus)
Authors: Shephard Alexander M. , Aksenov Vadim , Tran Jonathan , Nelson Connor J. , Boreham Douglas R. , Rollo C. David
Published: September 2018

Exposure to low-dose ionizing radiation can have positive impacts on biological performance—a concept known as hormesis. Although radiation hormesis is well-documented, the predominant focus has been medical. In comparison, little research has examined potential effects of early life radiation stress on organismal investment in life history traits that closely influence evolutionary fitness (eg, patterns of growth, survival, and reproduction). Evaluating the fitness consequences of radiation stress is important, given that low-level radiation pollution from anthropogenic sources is considered a major threat to natural ecosystems. Using the cricket ( Acheta domesticus), we tested a wide range of doses to assess whether a single juvenile exposure to radiation could induce hormetic benefits on lifetime fitness measures. Consistent with hormesis, we found that low-dose juvenile radiation positively impacted female fecundity, offspring size, and offspring performance. Remarkably, even a single low dose of radiation in early juvenile development can elicit a range of positive fitness effects emerging over the life span and even into the next generation.
Nonrelative sliding gear mechanism based on function-oriented design of meshing line functions for parallel axes transmission
Authors: Chen Zhen , Ding Huafeng , Zeng Ming
Published: September 2018

In this article, the design of a nonrelative sliding gear mechanism for parallel axes transmission is presented. First, the general meshing line functions were actively designed for the nonrelative sliding transmission between parallel axes. The parametric equations of contact curves on the driving and driven gears were deduced by the coordinate transformations of function-oriented design of meshing line functions. The meshing between two contact curves on driving and driven gears follows the principle of space curve meshing. Based on two types of motion equations of meshing points, the parametric equations of driving and driven tooth surfaces were deduced according to the helical motion along the calculated contact curves. According to the calculation equations, two pairs of numerical examples were designed and material prototype samples were fabricated to experimentally validate the kinematic performances. After the two types of meshing line motion functions for nonrelative sliding meshing for parallel axes transmission were analyzed, a tooth contact comparative analysis was carried out between the nonrelative sliding gears with uniform motion of meshing points and involute gears, exhibiting better performances. This article introduces a new design method of nonrelative sliding gear mechanism for parallel axes transmission based on function-oriented design of meshing line functions.
Treatment of Injuries to the Subaxial Cervical Spine: Recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU)
Authors: Schleicher Philipp , Kobbe Philipp , Kandziora Frank , Scholz Matti , Badke Andreas , Brakopp Florian , Ekkerlein Helmut , Gercek Erol , Hartensuer Rene , Hartung Philipp , Jarvers Jan-Sven , Matschke Stefan , Morrison Robert , Müller Christian W , Pishnamaz Miguel , Reinhold Maximilian , Schmeiser Gregor , Schnake Klaus John , Stein Gregor , Ullrich Bernhard , Weiss Thomas , Zimmermann Volker
Published: September 2018

Study Design:

Expert consensus.

Objectives:

To establish treatment recommendations for subaxial cervical spine injuries based on current literature and the knowledge of the Spine Section of the German Society for Orthopaedics and Trauma.

Methods:

This recommendation summarizes the knowledge of the Spine Section of the German Society for Orthopaedics and Trauma.

Results:

Therapeutic goals are a stable, painless cervical spine and protection against secondary neurologic damage while retaining maximum possible motion and spinal profile. The AOSpine classification for subaxial cervical injuries is recommended. The Canadian C-Spine Rule is recommended to decide on the need for imaging. Computed tomography is the favoured modality. Conventional x-ray is preserved for cases lacking a “dangerous mechanism of injury.” Magnetic resonance imaging is recommended in case of unexplained neurologic deficit, prior to closed reduction and to exclude disco-ligamentous injuries. Computed tomography angiography is recommended in high-grade facet joint injuries or in the presence of vertebra-basilar symptoms. A0-, A1- and A2-injuries are treated conservatively, but have to be monitored for progressive kyphosis. A3 injuries are operated in the majority of cases. A4- and B- and C-type injuries are treated surgically. Most injuries can be treated with anterior plate stabilization and interbody support; A4 fractures need vertebral body replacement. In certain cases, additive or pure posterior instrumentation is needed. Usually, lateral mass screws suffice. A navigation system is advised for pedicle screws from C3 to C6.

Conclusions:

These recommendations provide a framework for the treatment of subaxial cervical spine Injuries. They give advice about diagnostic measures and the therapeutic strategy.
The effect of tourniquet type and thigh conicity on the length of hamstring autograft
Authors: Çatma Mehmet Faruk , Öztürk Alper
Published: September 2018

Purpose:

We studied the effect of using wide contoured pneumatic tourniquet (PT) versus ultra-narrow sterile exsanguination tourniquet (SET) on the length of hamstring autograft for anterior cruciate ligament (ACL) reconstruction in patients with tubular and conical thighs.

Methods:

Fifty-eight patients undergoing ACL reconstruction between 2012 and 2013 were assigned to either SET or PT groups. We measured the tendon graft length and width as well as the patients’ height, weight, and thigh circumference of 10 cm proximal to the patella and the distance from the anterior–superior iliac spine to the medial malleolus (ASIS-MM). We defined the ratio between the ASIS-MM and the thigh circumference as the conicity index (CI). All grafts were measured after folding into half, and the found value was recorded as functional graft length (FGL). Tendon graft dimensions were correlated with the individual anthropometric data and with CI in each of the groups.

Results:

PT was used in 34 patients and SET on 24 patients. FGL was 12.7 ± 0.84 mean + standard deviation for the SET group versus 11.5 ± 1.61 for the PT group ( p = 0.0011) with a strong positive correlation between FGL and CI for the PT group ( R2 = 0.625; p = 2.6 × 10−8) but nonsignificant correlation for the SET ( R2 = 0.222). Graft thickness was correlated with the patient age ( R2 = 0.450) but not with CI or type of tourniquet used. We found the CI to be a better measure of thigh conicity than thigh circumference, length, height, weight, or body mass index individually.

Conclusion:

We conclude that using the SET which occupies less space on the thigh yielded significantly longer hamstring autologous ACL graft compared to the PT and the FGL became essentially independent from the CI when the SET was used.
Frequency domain multiparameter acoustic inversion for transversely isotropic media with a vertical axis of symmetry
Authors: Djebbi Ramzi , Alkhalifah Tariq
Published: September 2018

Multiparameter full-waveform inversion for transversely isotropic media with a vertical axis of symmetry (VTI) suffers from the trade-off between the parameters. The trade-off results in the leakage of one parameter’s update into the other. It affects the accuracy and convergence of the inversion. The sensitivity analyses suggested a parameterization using the horizontal velocity [Formula: see text], Thomsen’s parameter [Formula: see text], and the anelliptic parameter [Formula: see text] to reduce the trade-off for surface recorded seismic data. We aim to invert for this parameterization using the scattering integral (SI) method. The available Born sensitivity kernels, within this approach, can be used to calculate additional inversion information. We mainly compute the diagonal of the approximate Hessian, used as a conjugate-gradient preconditioner, and the gradients’ step lengths. We consider modeling in the frequency domain. The large computational cost of the SI method can be avoided with direct Helmholtz equation solvers. We applied our method to the VTI Marmousi II model for various inversion strategies. We found that we can invert the [Formula: see text] accurately. For the [Formula: see text] parameter, only the short wavelengths are well-recovered. On the other hand, the [Formula: see text] parameter impact is weak on the inversion results and can be fixed. However, a good background [Formula: see text], with accurate long wavelengths, is needed to correctly invert for [Formula: see text]. Furthermore, we invert a real data set acquired by CGG from offshore Australia. We simultaneously invert all three parameters using our inversion approach. The velocity model is improved, and additional layers are recovered. We confirm the accuracy of the results by comparing them with well-log information, as well as looking at the data and angle gathers.
Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline
Authors: Fakhry Carole , Lacchetti Christina , Rooper Lisa M. , Jordan Richard C. , Rischin Danny , Sturgis Erich M. , Bell Diana , Lingen Mark W. , Harichand-Herdt Seema , Thibo John , Zevallos Jose , Perez-Ordonez Bayardo
Published: September 2018

Purpose

The College of American Pathologists produced an evidence-based guideline on testing, application, interpretation, and reporting of human papillomavirus (HPV) and surrogate marker tests in head and neck carcinomas that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership.

Methods

The College of American Pathologists HPV Testing in Head and Neck Carcinomas guideline was reviewed by ASCO content experts for clinical accuracy and by methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations.

Results

The ASCO Expert Panel determined that the recommendations from the HPV Testing in Head and Neck Carcinomas guideline, published in 2018, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the guideline and added minor qualifying statements.

Recommendations

It is recommended that HPV tumor status should be determined for newly diagnosed oropharyngeal squamous cell carcinomas. HPV tumor status testing may be performed by surrogate marker p16 immunohistochemistry either on the primary tumor or from cervical nodal metastases only if an oropharyngeal primary tumor is present. The threshold for positivity is at least 70% nuclear and cytoplasmic expression with at least moderate to strong intensity. Additional confirmatory testing may be done at the discretion of the pathologist and/or treating clinician. Pathologists should not routinely determine HPV tumor status in nonsquamous carcinomas of the oropharynx or non–oropharyngeal squamous cell carcinomas of the head and neck. When there is uncertainty of histologic type or whether a poorly differentiated oropharyngeal tumor is nonsquamous, HPV tumor status testing may be warranted and at the discretion of the pathologist and/or treating clinician. Additional information is available at: www.asco.org/head-neck-cancer-guidelines .
A multimodal intervention to enhance sexual function and quality of life (QOL) in hematopoietic stem cell transplant (HCT) survivors.
Authors: Fishman Sarah , Vanderklish Julie , Dizon Don S. , Traeger Lara , Park Elyse R. , Chen Yi-Bin Albert , McAfee Steven L. , Spitzer Thomas R. , DeFilipp Zachariah Michael , Temel Jennifer , El-Jawahri Areej
Published: September 2018

10013

Background: Although sexual dysfunction is a common long-term complication in allogeneic HCT survivors, interventions to address sexual dysfunction are lacking. Methods: We conducted a pilot study to assess the feasibility and preliminary efficacy of a multimodal sexual dysfunction intervention to improve sexual function in allogeneic HCT survivors. Transplant clinicians systematically screened all HCT survivors ≥ 3 months post-HCT for sexual dysfunction causing distress using the NCCN Survivorship Guidelines. Those who screened positive attended monthly intervention visits with trained study clinicians that focused on 1) assessing sexual dysfunction; 2) educating and empowering patients to address this topic; and 3) implementing therapeutic interventions. We used the PROMIS Sexual Function and Satisfaction Measure, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and Hospital Anxiety and Depression Scale (HADS) to assess sexual function, QOL, and mood at baseline and six months post-intervention, respectively. Results: 32.7% (49/150) of patients screened positive for sexual dysfunction causing distress. 95.9% (47/49) of patients who screened positive agreed to participate. We demonstrated significant improvement in patients’ satisfaction and interest in sex as well as sexual function including orgasm, erectile function, lubrication, and vaginal discomfort [Table]. Six of ten patients who were not sexually active prior to the intervention became sexually active post-intervention (P = 0.031). Patients reported improvement in their QOL and a trend toward lower depression [Table]. Conclusions: The multimodal intervention to address sexual dysfunction appears feasible with encouraging preliminary efficacy for improving sexual function, QOL, and mood in allogeneic HCT survivors. Clinical trial information: NCT02492100. [Table: see text]
New primary lung cancers after a head and neck cancer: The impact of radiation therapy and latency period on risk.
Authors: Jeurkar Chetan , Pompa Tiffany , Bauman Jessica Ruth , Jain Maneesh Rajiv , Ward Kristine Marie , Styler Michael
Published: September 2018

10015

Background: Patients with head and neck cancer (HNC) have an increased risk of developing a new primary lung cancer (NPLC). Our objective was to assess the critical latency period after HNC when the risk for a NPLC was highest and to see if radiation therapy (XRT) had an impact on this risk. Methods: This was a population based study of patients with HNC in the Surveillance, Epidemiology, and End Results (SEER) database. The risk of NPLC was calculated using standardized incidence ratios (SIR) and from this, the number needed to screen (NNS) was extrapolated. The cohort was separated by delivery of XRT and latency period of the NPLC. Results: There were a total of 4,209 NPLC from the cohort of 85,154 HNC patients. The SIR, NNS, observed/expected number of NPLC for both the no XRT and XRT groups are shown in table 1. As compared to the no XRT group, the XRT group had higher SIR and lower NNS values across all latency periods. The highest SIR for both the no XRT and XRT groups came between 1 and 3 years. Conclusions: In patients with HNC, the risk of developing a NPLC is associated with receiving XRT. This risk is highest within 10 years of the initial HNC diagnosis. The NNS was especially low for the XRT group, less than 100 for most latency periods. Since low dose computed tomography scans for lung cancer screening in smokers has a NNS of 217, screening for these patients should be considered, especially within 10 years of the primary HNC diagnosis. This may contribute to better survivorship care in these patients. [Table: see text]
Effect of exercise on quality of life (QoL) in 198 older patients with cancer: A URCC NCORP nationwide RCT.
Authors: Loh Kah Poh , Mohile Supriya Gupta , Cole Calvin , Fung Chunkit , Dunne Richard Francis , Lin Po-Ju , Cho Jonathan K. , Conlin Alison Katherine , Kuebler J. Phillip , Mustian Karen Michelle
Published: September 2018

10019

Background: Cancer and its treatment frequently impact QoL in patients. In older cancer patients, a small decrement in QoL is associated with significant functional impairment, disability, treatment discontinuation and decreased survival. Little is known about the role of exercise in improving QoL in older cancer patients undergoing active chemotherapy and the mechanistic association between inflammation and QoL. We conducted a secondary analysis of a nationwide phase III RCT to assess the effect of exercise on QoL in older cancer patients. Methods: We included 198 older cancer patients (aged ≥60 years) who were randomized to receive chemotherapy alone (C) or with EXCAP (Exercise for Cancer Patients). EXCAP is a home–based progressive aerobic and resistance training program. We used ANCOVA to evaluate the effect of EXCAP on QoL (measured by the Functional Assessment of Cancer Therapy-General, FACT-G, and -Cognitive Function, FACT-Cog). Baseline values, gender and chemotherapy duration were adjusted. We assessed associations between changes in QoL and changes in inflammatory cytokines. Results: Median age was 66.7 ± 2.3 years, 92% were female and 77% had breast cancer. In terms of chemotherapy, 3-week and 2-week regimens were used for 72% and 28%, respectively. EXCAP group had better social (p=0.02), emotional (p=0.04) and physical (p=0.03) well-being post-intervention than the C group. There was also a positive trend for improvement in functional, cognitive and overall well-being (Table 1). In the EXCAP group, improved social well-being was associated with decreases in the pro-inflammatory cytokine, IL-8 (r=0.30, p=0.03). Conclusions: Our analysis showed that exercise improves QoL in older cancer patients receiving active chemotherapy. Improvement in social well-being may be mediated by reducing inflammation. Physicians should consider incorporating exercise when prescribing chemotherapy for older adults with cancer. Clinical trial information: NCT00924651. [Table: see text]
Phase III, randomized study of first-line trastuzumab emtansine (T-DM1) ± pertuzumab (P) vs. trastuzumab + taxane (HT) treatment of HER2-positive MBC: Final overall survival (OS) and safety from MARIANNE.
Authors: Perez Edith A. , Barrios Carlos H. , Eiermann Wolfgang , Toi Masakazu , Im Young-Hyuck , Conte Pier Franco , Martin Miguel , Pienkowski Tadeusz , Pivot Xavier B. , Burris Howard A. , Hoersch Silke , Patre Monika , Ellis Paul Anthony
Published: September 2018

1003

Background: In MARIANNE (NCT01120184), patients with HER2-positive advanced breast cancer were randomized to trastuzumab + docetaxel or paclitaxel (HT; n=365), T-DM1 + placebo (T-DM1; n=367), or T-DM1 + P (T-DM1 + P; n=363) as first-line therapy. In the primary analysis, T-DM1–based treatment exhibited noninferior, but not superior, progression-free survival relative to HT (Perez EA, et al. J Clin Oncol 2016). OS was similar between treatments in the first interim analysis. Here we report OS from the final descriptive analysis. Methods: Enrolled patients had centrally assessed HER2-positive (IHC3+ or ISH+) progressive/recurrent locally advanced breast cancer or previously untreated MBC with a ≥6-month interval since (neo)adjuvant treatment with taxanes or vinca alkaloids. Results: At the clinical cutoff date of May 15, 2016, median follow-up was 54 months and 512 patients had died. Median OS was 50.9, 53.7, and 51.8 months with HT, T-DM1, and T-DM1 + P, respectively (Table). A sensitivity analysis in which HT-treated patients who received T-DM1 and/or P after disease progression (n=85) were censored prior to treatment switch found similar results. There were numerically fewer grade ≥3 adverse events (AEs) with T-DM1. Conclusions: With this longer follow-up, the T-DM1 safety profile was consistent with the primary analysis and prior experience. While OS was similar across treatment arms, a median OS of 53.7 months and fewer grade ≥3 AEs (vs other arms) supports T-DM1 as an effective and tolerable alternative first-line treatment for HER2-positive MBC patients. Clinical trial information: NCT01120184. [Table: see text]
Utility of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in hematopoietic stem cell transplantation (HSCT).
Authors: Mumby Patricia B. , Doyle Todd , Adams William , Hicks Elliott B. , Thilges Sarah , Mai Hanh P. , Smith Scott E. , Rodriguez Tulio , Go Aileen , Marinier David , Stiff Patrick J.
Published: September 2018

10046

Background: The SIPAT is used to assess psychosocial risk in solid organ transplants but data in HSCT is lacking. We examined if pre-HSCT SIPAT scores predict mortality, morbidity, length of stay (LOS) and number of hospitalizations over a 1 year period. Methods: 89 adult HSCT (59% autologous, 38% allogeneic) pts from an academic medical center underwent the SIPAT pre-HSCT. Additional data were obtained on Day 0, and 3-, 6-, and 12-months. Univariable Cox proportional hazards models assessed the instantaneous risk of mortality at any given time after Day 0 as a function of baseline pt characteristics and the SIPAT score. Results: TheSIPAT categorized 28%, 66% and 5.7% respectively of the pts as excellent (E), good (G), and high risk (HR) candidates. One year post HSCT, 76% of E, 72% of G, and 40% of HR candidates were alive. Higher SIPAT scores were a significant predictor of mortality. Compared to E candidates, the HR candidates were 5.94 (95% CI: 1.31-26.81) times more likely to die any time after Day 0 – even after controlling for pts’ comorbidity index ( p = .02). Similarly, compared to G candidates, HR pts were 4.81 (95% CI: 1.33-17.47) times more likely to die even after controlling for pts’ comorbidity index ( p = .01). There was no difference between the G and E candidates on univariable ( p = .75) or multivariable analysis controlling for comorbidity index score ( p = .72). For every 1 point increase in pts’ adherence score, the risk of death was expected to decline by approximately 14% ( HR = 0.86, 95% CI: 0.78 – 0.96; p = .01). SIPAT items that predicted mortality were depression ( p = .02), deceptive behavior ( p < .001) and moderate alcohol abuse ( p < .001). In linear regression analysis, higher SIPAT score was associated with longer LOS ( p = .04) but not infection ( p = .23), GVHD ( p = .40), or number of hospitalizations ( p = .73). Because there were only 18 mortality events, multivariable analyses were limited. Future research will examine the effect of SIPAT on time to death controlling for other pt comorbidities. Conclusions: We found the SIPAT was able to predict mortality and LOS in HSCT pts. This finding if validated in a multi-center manner could be an important tool for HSCT pt selection.
Fear of recurrence among cancer survivors.
Authors: Jimenez Rachel B , Perez Giselle Katiria , Rabin Julia , Hall Daniel , Quain Katharine , Park Elyse , Peppercorn Jeffrey M.
Published: September 2018

10053

Background: Fear of cancer recurrence (FoCR) following definitive cancer therapy is often reported by patients, but little is known about who is most likely to be impacted, how FoCR influences emotional distress, and what interventions may mitigate patients’ FoCR. We sought to determine the prevalence of FoCR among cancer survivors and to evaluate potential predictors of FoCR in this population. Methods: As part of a comprehensive supportive care needs assessment, we evaluated the prevalence of FoCR among patients receiving follow-up cancer care at our institution as well as factors associated with FoCR. Elevated FoCR was measured with a single item: “I worry about my cancer coming back” rated on a 4-point Likert scale (1 = “not at all” to 4 = ”very much”); responses of 3 or 4 were considered positive for FoCR. Descriptive statistics were used to characterize patterns of FoCR. Chi-square and Fisher’s exact tests compared differences in emotional, clinical, and demographic characteristics between participants with and without FoCR, as well as interest in and knowledge of survivorship services. Results: Of 636 patients who completed the survey, 318/636 (50.0%) patients had curable cancer and had either completed cancer therapy or were completing maintenance treatment. On inquiry, 167/318 (53%) reported FoCR. Those with FoCR were more likely to be female (p < 0.002) and under the age of 70 (p < 0.003). They were also more likely to be sad (25% vs. 14%, p < 0.015), anxious (40% vs. 21% p < 0.0005), feel uncertain about the future (30% vs. 14%, p < 0.0005), have problems managing stress (26% vs. 13%, p < 0.003), and were more likely to worry about dying (55% vs. 8%, p < 0.0001) and to fear another cancer (74% vs. 8% p < 0.0001). Education level, cancer type, knowledge of and interest in support services, and survivorship care plan receipt were not associated with FoCR. Conclusions: Patient FoCR is prevalent among more than half of survivors of cancer and is associated with emotional distress that is insufficiently addressed by survivor care planning and supportive services. Clinicians can and should screen for and address this issue. Future research is needed to develop and test interventions, beyond care plans, to address FoCR in both low risk and high risk patient populations.
Risk tolerance and attitudes toward chemotherapy: Who chooses palliative treatment when cure is possible?
Authors: LeBlanc Thomas William , Scherr Karen , Wang Annabel , Lemmon Monica , Ubel Peter A.
Published: September 2018

10054

Background: Many patients with acute myeloid leukemia (AML) face a difficult choice about whether to receive palliative chemotherapy or high-dose, potentially-curative chemotherapy that poses a risk of early death. How people weigh these factors in decision-making is unknown. We hypothesized that the possibility of cure primarily drives decision-making, regardless of treatment risk. Methods: We designed an electronic survey describing two treatment paths: (1) high-dose chemotherapy with possibility of cure but a 10% risk of early death, and (2) palliative chemotherapy with no chance of cure but no risk of early death. We recruited respondents via Amazon MTurk and presented 7 scenarios in random order, varying only the likelihood of cure associated with high-dose chemotherapy. Subjects rated their preferred treatment on a 4-point Likert scale. We assessed numeracy and attitudes toward chemotherapy using validated scales, and employed attention checks for quality assurance. Results: 100 subjects completed the survey (median age 30.5; 52 female, 85 Caucasian). 46 (46%) had at least a bachelor’s degree and numeracy was generally high (median 4.75 out of 6). Respondents’ preferences for intensive chemotherapy varied with likelihood of cure, however some displayed a fixed preference for either curative or palliative treatment throughout, regardless of benefit level. For example, given a 50% likelihood of cure 20 respondents (20%) still preferred palliative therapy; similarly, with only a 1% likelihood of cure 28 respondents (28%) still preferred high-dose chemotherapy. In a multivariable model, preference for palliative chemotherapy was significantly predicted by subjects’ scores on the attitudes toward chemotherapy scale (p < 0.001), controlling for age, education, and numeracy. Conclusions: Contrary to our hypothesis, a significant proportion of subjects preferred palliative chemotherapy, even in scenarios where high-dose chemotherapy confers a high likelihood of cure. Pre-existing attitudes toward chemotherapy appear to drive patients’ decision-making, even when treatments are potentially curative. This finding may have significant implications for risk communication in oncology.
Multicenter, randomized phase II trial of physical activity (PA), metformin (Met), or the combination on metabolic biomarkers in stage I-III colorectal (CRC) and breast cancer (BC) survivors.
Authors: Meyerhardt Jeffrey A. , Irwin Melinda L , Jones Lee , Zhang Sui , Campbell Nancy , Brown Justin C. , Pollak Michael N. , Sorrentino Alexandra , Cartmel Brenda , Harrigan Maura , West Miranda , Tolaney Sara M. , Yung Rachel Lynn , Winer Eric P. , Ng Kimmie , Abrams Thomas Adam , Fuchs Charles S. , Sanft Tara Beth , Douglas Pamela , Ligibel Jennifer A.
Published: September 2018

10059

Background: Observational data demonstrate an inverse relationship between PA and Met to disease outcomes in CRC & BC pts. A mechanism that these could impact cancer recurrence and mortality is hypothesized to involve insulin and related growth factors. We investigated the effects of PA, Met or the combination on metabolic biomarkers in CRC & BC pts. Methods: In a phase 2 RCT, stage I-III CRC & BC survivors at least 2 months from completing standard therapy (excluding hormone rx or trastuzumab) were randomized to PA, Met, PA + Met or control. Major eligibility included absence of recurrence or diabetes (glucose < 160 (random) or < 126 (fasting) mg/dl) and exercising < 120 min/wk. The PA intervention consisted of supervised aerobic training at least 2 x /wk. Metformin dosing was 850 mg 1x/day titrated to 850 mg 2x/day after 2 wks if tolerated. Interventions were 12 weeks in duration. Fasting bloods at baseline & 12 wks were analyzed for insulin (1oendpoint), leptin, IGF1, IGFBP1 & IGFBP3. Results: 139 pts were enrolled: 62% BC/38% CRC; 83% female; median BMI 28.3; median 2 yrs from dx; median age 56 (range 34-79). 107 pts completed assigned therapy. Pts in PA and PA + Met arms increased PA by 166 and 140 min/wk vs 30 min/wk in controls (both P<0.0001). Pts in the Met and PA + Met arms lost weight vs controls (-1.41 and -0.91 kg vs + 1.97 kg, both P <0.0001). Both interventions had impact on metabolic biomarkers (Table). Conclusions: PA and Met both led to significant changes in insulin and other biomarkers in CRC & BC survivors with potential synergistic effect on leptin with dual intervention. Clinical trial information: NCT01340300. [Table: see text]
Chemotherapy-induced ovarian failure (CIOF) in young women with early breast cancer (EBC).
Authors: Furlanetto Jenny , Thode Christian , Bassy Martina , Denkert Carsten , Hanusch Claus , Huober Jens Bodo , Jackisch Christian , Kummel Sherko , Schneeweiss Andreas , Untch Michael , Fasching Peter A. , Karn Thomas , Marme Frederic , van Mackelenbergh Marion , Müller Volkmar , Schem Christian , Von Minckwitz Gunter , Strik Dominika , Nekljudova Valentina , Loibl Sibylle
Published: September 2018

10068

Background: Women ≤45 years (yrs) treated with chemotherapy (CT) for EBC have a high risk of developing CIOF. Awareness of CIOF is essential for young women. Methods: 740 patients (pts) aged ≤45yrs treated with anthracycline or taxane-based CT for EBC from 4 German neoadjuvant/adjuvant trials were included. Blood samples were collected at baseline (N=740), end of treatment (EOT n=740), 6 (n=177), 12 (n=113), 18 (n=69), 24 (n=47) months (m) after EOT. Only samples collected in a time sequence were included. Estradiol (E2), Follicle-Stimulating Hormone (FSH) and Anti-Müllerian Hormone (AMH) were centrally assessed. CIOF was defined as FSH >12.4IU/l and E2 <52.2ng/ml and was analysed per timepoint and according to clinical and treatment-related variables. Results: Median age was 40yrs (range 21-45); 57.2% had BMI 18.5-<25, 41.1% ≥25; 32% had luminal, 35.9% HER2+, 32.0% triple-negative BC. Median hormone levels at baseline for pts <30yrs vs 30-40yrs vs ≥40yrs were: FSH 5.2IU/I vs 5.6IU/I vs 6.4IU/I; E2 101ng/l vs 86ng/l vs 88ng/l; AMH 2.14ng/ml vs 1.58ng/ml vs 0.53ng/ml. 85.7% of pts had CIOF at EOT, 62.2% at 6m, 54.0% at 12m, 43.5% at 18m, 38.3% at 24m. Similar results were observed in 47 pts with all timepoint samples available. Older vs younger pts had more frequently CIOF at EOT (≥40yrs 94.6%, 30-40yrs 82.0%, <30yrs 50.0%, p<0.001). CIOF at EOT was not influenced by BMI. CT agents impacted the rate of CIOF (p<0.001; Table 1). Higher rate of CIOF was associated with longer CT duration (12w 58.3%, 16-18w 94.5%, 24w 82.1%; p<0.001) and with dose-dense (ddEC-ddD, weekly PM(Cb), intense-dd (idd) EnPC) vs conventional dosed CT (P/nP-EC q3w, P, Cz) (94.5% vs 78.6%; p<0.001). Conclusions: The majority of young women experienced CIOF after CT for EBC. After 2 yrs 62% of the pts returned to premenopausal hormone levels. Age, CT regimen, duration and density influenced the rate of CIOF and should be taken into account when counseling young women who desire to maintain ovarian function. [Table: see text]
Fatigue and health behaviors in cancer survivors: A cross-sectional population based study.
Authors: Matias Margarida , Baciarello Giulia , Neji Mohamed , Michiels Stefan , Partridge Ann H. , Bendiane Marc Karim , Fizazi Karim , Ducreux Michel , Andre Fabrice , Luis Ines Maria Vaz Duarte
Published: September 2018

10069

Background: A substantial proportion of breast, colo-rectal and prostate cancer patients (pts) can expect long term disease free survival after their primary treatment. Among those, fatigue commonly persists after diagnosis (dx) and can be debilitating. In this study, we evaluated the incidence of fatigue 2 years (y) after cancer dx and its association with health behaviors. Methods: We used a French population based cross-sectional study, which included a representative sample of pts from 12 cancer types (VICAN2). VICAN2 surveyed 4347 pts 2 y after dx. There is a 99% completion rate of fatigue related questions. For this study, we included 2017 pts with breast (1237), colo-rectal (348) and prostate (432) cancer without evidence of metastases at dx or relapse 2y after dx and with fatigue information. Severe fatigue was defined as average score of EORTC QLQC30 fatigue subscale ≥40 at 2y after dx. There were <1% of missing values in the evaluated covariates. Multivariate logistic regression models looked at associations of fatigue with heatlh behaviors (Δ in exercise since dx, exercise at diagnosis, body mass index (BMI), Δ since dx, smoking), age, gender, comorbidities, education, employment, cancer type, radiation, chemotherapy, hormonal therapy. Results: 52% of pts reported severe fatigue at 2 y after dx (median fatique score: 44, range: 0-100). 2 y after dx, 47% of pts either stopped or decrease exercise and 16% had a ≥ 10% change in BMI. Factors associated with fatigue included health behaviors (Table), but also age (adjusted odds ratio [ aOR] for severe fatigue, 95% confidence interval [95% CI]: 0.97, 0.96-0.98), gender ( aOR, 95 CI male vs. female: 0.5, 0.3-0.8), comorbidities ( aOR, 95 CI yes vs. no: 2.0, 1.6-2.4) and treatment type ( aOR, 95 CI radiation vs. no: 1.5, 1.1-2.0). Conclusions: Fatigue continues to be a substantial problem for cancer survivors 2 y after dx. Some factors that may contribute to persistent fatigue (health behaviors) may be amenable to interventions. [Table: see text]
Genitourinary disease risks among 5-year ovarian cancer survivors in a population-based cohort study.
Authors: Hashibe Mia , Chen Yuji , Blackburn Brenna , Wan Yuan , Rowe Kerry G. , Snyder John , Deshmukh Vikrant , Newman Michael , Fraser Alison M , Werner Theresa Louise , Smith Ken R , Gaffney David K. , Doherty Jennifer , Ganz Patricia A.
Published: September 2018

10073

Background: In the US, there are approximately 235,200 ovarian cancer survivors today. Five-year survival for ovarian cancer has increased from 36% for women who were diagnosed in 1975-1977 to 46% for women diagnosed between 2005-2011. Long term follow-up studies among ovarian cancer survivors are uncommon and late effects have not been well characterized in a population-based cohort. Although genitourinary complications during treatment are well known, long term impacts need to be investigated. Methods: A total of 602 first primary invasive ovarian cancer cases diagnosed between 1996-2012 who survived for > 5 years were identified in the Utah Population Database and compared to a general population cohort of women. Genitourinary disease diagnoses were identified through ICD codes from hospital electronic medical records and statewide ambulatory surgery and inpatient data. Cox regression models were used to estimate hazard ratios for disease risks by time since cancer diagnosis with adjustments on matching factors, baseline BMI, baseline Charlson Comorbidity Index (CCI), and race. Results: The overall risk of genitourinary diseases for ovarian cancer patients in comparison to the general population cohort was 1.51 (95%CI = 1.30-1.74) 5-10 years after cancer diagnosis. Approximately 54.6% of ovarian cancer survivors were diagnosed with a genitourinary disease 5-10 years after cancer diagnosis. The most common genitourinary diseases among the ovarian cancer survivors were urinary tract infections (10.1%), acute renal failure (5.5%), and chronic kidney disease (4.4%). The greatest risks were observed for hydronephrosis (HR = 10.65, 95%CI = 3.68-30.80), pelvic peritoneal adhesions (HR = 5.81, 95%CI = 1.11-30.39), cystitis and urethritis (HR = 2.67, 95%CI = 1.21-6.38), and acute renal failure (HR = 2.30, 95%CI = 1.36-3.88). Conclusions: Ovarian cancer survivors experience increased risks of various genitourinary diseases in the 5-10 year period following cancer diagnosis. Understanding the multimorbidity trajectory among ovarian cancer survivors is of vital importance to improve their clinical care after cancer diagnosis and allow for increased attention to these potential late effects.
Immediate-term chemotherapy-related cognitive impairment (CRCI) following administration of intravenous (IV) chemotherapy.
Authors: Khan Omar Farooq , Cusano Ellen R. , Raissouni Soundouss , Pabia Mica , Haeseker Johanna , Bosma Nicholas Adam , Ko Jenny J. , Kumar Aalok , Yip Steven , Vickers Michael M. , Tang Patricia A.
Published: September 2018

10084

Background: The acute impact of chemotherapy on cognition is unknown. This study utilized performance on the psychomotor vigilance task (PVT) and trail-making test B (TMT) to assess CRCI immediately following chemotherapy administration. Methods: Patients aged 18-80 years receiving first-line IV chemotherapy for any stage of breast or colorectal cancer were eligible. Patients with brain metastases, neurologic disorders or allergic reactions to chemotherapy were excluded. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Paired Wilcoxon Rank Sum tests were used to assess change in median PVT reaction time, TMT completion time, TMT errors and PVT lapses. A priori, an increase in median PVT reaction times by over 20 ms (approximating reaction time changes with blood alcohol concentrations of 0.04 to 0.05 g%) was considered a clinically relevant change. Results: 144 patients (74 breast, 70 colorectal, median age 55.5 years) were tested. Post-chemotherapy, median PVT reaction time slowed by an average of 12.4 ms ( p = 0.01). Post-chemotherapy median PVT times slowed by over 20 ms in 59 patients (40.9%). TMT completion post-chemotherapy was faster by an average of 6.1 seconds ( p < 0.001). No differences were seen in TMT errors ( p = 0.417) or PVT lapses ( p = 0.845). Change in median PVT reaction time was not associated with age, gender, number of prior chemotherapy cycles, peripheral neuropathy grade, self-reported symptoms (anxiety, fatigue or depression). Change in median PVT reaction time was also not significantly associated with use of any specific chemotherapeutic drug or class, including paclitaxel (which includes ethanol as an excipient). Conclusions: Median PVT reaction time was significantly slower immediately after chemotherapy compared to a pre-chemotherapy baseline, and impairment correlating to effects of alcohol was seen in 41% of patients. This effect appears independent of age, self-reported symptoms or prior chemotherapy cycles. Further studies assessing functional impact of immediate-term CRCI are warranted.
Impact of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) on time to progression and overall survival (OS) in metastatic colorectal cancer (mCRC) patients.
Authors: Kurk Sophie , Peeters Petra H.M. , Stellato Rebecca K. , Dorresteijn Bram , Jourdan Marion , Creemers Geert-Jan , Erdkamp Frans , de Jongh Felix E. , Kint Petrus Alouisius Maria , Poppema Boelo Jan , Radema Sandra Anita , Simkens Lieke H , Tanis Bea , Tjin-A-Ton Manuel Lucien Roy , Van Der Velden Ankie , Punt Cornelis J. A. , Koopman Miriam , May Anne Maria
Published: September 2018

10087

Background: Evidence for a strong link between skeletal muscle depletion and poor outcomes in mCRC is growing. However, the impact of SMI changes over time on progression and OS during palliative systemic Tx is not known. The CAIRO3 study (Simkens et al. Lancet 2015) randomized 556 mCRC patients after 6 cycles capecitabine+oxaliplatin+bevacizumab (CAPOX-B) to maintenance CAP-B Tx (Main) vs. observation (Obs). Upon 1st disease progression (PD1), CAPOX-B or other treatment was reintroduced until 2nddisease progression (PD2). This is the first analysis using scan data of multiple time-points to investigate SMI changes during palliative systemic treatment Tx and its association with survival. Methods: 1227 CT-scans of a random selection of 416 CAIRO3 patients (mean age 64±9 years, Main n = 206; Obs n = 210) were analyzed for SMI (skeletal muscle area at the L3 level in cm2/m2). Using mixed model analysis, SMI changes were analyzed for two intervals; interval 1: from randomization to PD1, and interval 2: from PD1 to PD2. Three Cox regression models were used to study the association between SMI loss and time to PD2 and death for interval 1, and time to death for interval 2. Main and Obs groups were combined in the analyses since the p-value for interaction was not significant. Hazard ratios (HR) were reported per 2 units change in SMI. Results: Median times from randomization to PD1, PD2 and death were 7.7, 13.5 and 24 months resp. During interval 1 (less intensive or no Tx) patients gained SMI on average (1.2 units; 95%CI 0.6-1.8), but 23% of patients still lost SMI. SMI loss was associated with shorter time to PD2 (HR 0.88; 0.81-0.98, p= .01), but not with shorter OS (HR 0.94; 0.86-1.02, p= .17). During interval 2 (more intensive Tx) average SMI loss was -2.2 units ( 1.5-2.8) and 63% of patients lost SMI. SMI loss was associated with shorter OS (HR 0.73; 0.62-0.86, p< .00). Conclusions: Loss of SMI was related to shorter time to progression during first line less intensive main Tx or obs and shorter overall survival during more intensive reinduction Tx. This large longitudinal study suggests that SMI preservation may be a therapeutic goal. Clinical trial information: NCT00442637.
Comprehensive study of risk factors for chemotherapy-induced nausea and vomiting in cancer patients receiving cisplatin-based chemotherapy: A TRIPLE pharmacogenomics study.
Authors: Ayuhara Hideaki , Tsuji Daiki , Yokoi Mari , Suzuki Kenichi , Kawasaki Yohei , Nakao Masahiko , Kogure Yuki , Shibata Kazuhiko , Hayashi Toshinobu , Hirai Keita , Inoue Kazuyuki , Hama Toshihiro , Takeda Koji , Nishio Makoto , Itoh Kunihiko
Published: September 2018

10091

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most unpleasant adverse effects of chemotherapy. Resistance to prophylactic antiemetic treatment is problematic, with 30%–50% of patients experiencing unsatisfactory control. Younger age and female sex are well-known risk factors for CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response. Methods: This study included a subset of patients previously enrolled in a randomised controlled trial. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study’s efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR0-24) and delayed (CR24-120) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables. Results: In this genetic polymorphism association study, 156 patients with solid cancer were evaluated. Multivariate logistic regression analysis revealed that ERCC1 8092AA (odd ratio [OR]: 11.251; 95% confidence interval [CI]: 1.741–72.712, P = 0.011) and female sex (OR = 3.630; 95% CI = 1.138–11.578, P = 0.029) were significant predictors of CR0-24. No significant association of CR24-120 with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis. Conclusions: ERCC1 polymorphism might be influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy. Clinical trial information: 000009335.
Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy.
Authors: Pedrazzoli Paolo , Cereda Emanuele , Cappello Silvia , Colombo Sara , Klersy Catherine , Imarisio Ilaria , Turri Annalisa , Caraccia Marilisa , Verlicchi Alberto , Benazzo Marco , Corbella Franco , Caccialanza Riccardo
Published: September 2018

10098

Background: The benefit of systematic use of oral nutritional supplements (ONS) in addition to nutritional counseling in head and neck cancer (HNC) patients undergoing radiotherapy (RT) has not still been properly assessed. Methods: In a single-center, randomized, pragmatic, parallel-group controlled trial (ClinicalTrials.gov: NCT02055833; February 2014 - August 2016), 159 newly diagnosed HNC patients suitable for to RT regardless of previous surgery and induction chemotherapy were randomly assigned to nutritional counseling in combination with omega-3 enriched ONS (N = 78) or without ONS (N = 81) from the start of RT and continuing for up to 3 months after its end. The primary endpoint was the change in body weight at the end of RT. Secondary endpoints included changes in protein-calorie intake, muscle strength, body composition and quality of life (EORTC-QLQ-C30) over the study time points and anti-cancer treatment tolerance. Results: In patients in whom all the variables could be assessed, counseling plus ONS (N = 67) resulted in smaller loss of body weight than nutritional counseling alone (N = 69; mean difference, 1.6 kg [95%CI, 0.5 to 2.7]; P = 0.006). Imputation of missing outcomes provided consistent findings. In the ONS-supplemented group, higher protein-calorie intake and improvement in quality of life over time were also observed (P < 0.001 for all). The use of ONS reduced the need for changes in scheduled anti-cancer treatments (i.e. for RT and/or systemic treatment dose reduction or complete suspension, HR = 0.40 [95%CI, 0.18 to 0.91], P = 0.029). Nine patients reported gastrointestinal intolerance to ONS. Conclusions: In HNC patients undergoing RT or RT plus systemic treatment, and receiving nutritional counseling, weight loss could not be completely prevented, but the use of ONS resulted in better weight maintenance, increased protein-calorie intake, improved quality of life and better anti-cancer treatment tolerance. Clinical trial information: NCT02055833.