Effect of Enrichment Devices on Aggression in Manipulated Nude Mice.

Agonistic behavior in group-housed male mice is a recurring problem in many animal research facilities. Common management procedures, such as the removal of aggressors, are moderately successful but often fail, owing to recurrence of aggressive behavior among cagemates. Studies have incorporated enrichment devices to attenuate aggression, but such devices have had mixed results. However, these studies did not include research manipulations when assessing the benefits of various enrichment devices. We obtained 100 male athymic nude mice and studied the efficacy of various enrichment devices, including cotton squares, paper rolls, shredded paper, nylon bones, and a mouse house and wheel combination in the reduction of fighting during an ongoing study that involved randomization followed by prostate and intratibial injections. Groups were evaluated according to a numerical grading system for wound assessment. Examination of the data revealed that the enrichment devices had no effect on the presence of wounds, thus none of the devices tested affected fighting in nude mice. However, when mice began experimental use, fight wounds increased significantly at cage change and after randomization, reflecting a disruption of existing social hierarchies. Therefore, in the context of an actual research study that involves common manipulations, the specific enrichment device had less effect on aggression in male nude mice than did the destruction and reconstruction of social structures within each group.

Self-reported sleep disturbance in patients with advanced cancer: Frequency, intensity, and factors associated with response to outpatient supportive care consultation--A preliminary report.

OBJECTIVES: Self-reported sleep disturbance (SD) is a distressing symptom in patients with advanced cancer. There are limited data on the treatment of SD and predictors to response of SD to outpatient supportive care clinic (OPC) consultation. The aims of our study was to determine the frequency, intensity, and correlates of SD as assessed with the Edmonton Symptom Assessment System (ESAS) sleep item at the time of initial consultation and identify the predictors of improvement in SD at follow-up. METHODS: We reviewed the records of consecutive patients with advanced cancer presenting to the OPC. ESAS scores were obtained at the initial and subsequent visits between January 2008 and February 2010. All patients underwent screening for SD (0-10 scale: 0 = best sleep, presence of SD defined as ≥ 3) and interdisciplinary assessment and treatment, including drug review, counseling, sleep hygiene review, and drug therapy. A response was defined as a 1-point improvement at the follow-up visit on the Edmonton Symptom Assessment Scale (ESAS) sleep item score. Baseline patient characteristics, medication use, and ESAS scores were analyzed to determine their association with response. RESULTS: The median age was 58 years, and 53% of patients were men. The most common cancer type was head and neck or lung (36%). Of the 442 patients, 330 had baseline SD (score ≥ 3/10, 75%). Median and mean (standard deviation) baseline SD scores were 5 and 5.1 (2.9). The multivariable regression model found the intensity of baseline ESAS sleep item scores to be associated with baseline sedative use, baseline ESAS pain scores, baseline ESAS fatigue scores, baseline ESAS feeling of well-being scores, and sedative use (R 2 = 0.22). Sleep disturbance response at first follow-up was seen in 196 of 330 patients (59%). Moderate to high SD score and anxiety at initial visit with odds ratios (OR) of 2.53 (p = 0.0007) and 1.59 (p = 0.048), respectively, were associated with a response. SIGNIFICANCE OF RESULTS: Both the frequency and severity of SD were high. Response to supportive care consultation was substantial. The severity of SD and anxiety at the initial visit predicted a response at first follow-up. Further research is needed.

Hepatitis C virus screening in patients with cancer receiving chemotherapy.

PURPOSE: Reactivation of hepatitis C virus (HCV) replication can occur in patients receiving immunosuppressive therapy. We aimed to determine the prevalence and predictors of HCV screening at the onset of chemotherapy among patients with cancer. METHODS: We conducted a retrospective cohort study of adults with cancer who were newly registered at MD Anderson Cancer Center from January 2004 to April 2011 and received chemotherapy. The primary study outcome was HCV antibody (anti-HCV) screening at chemotherapy onset. We calculated screening prevalence and predictors by comparing characteristics of screened and unscreened patients using multivariable logistic regression. RESULTS: A total of 141,877 new patients with cancer were registered at MD Anderson during the study period, of whom 16,773 (11.8%) received chemotherapy and met inclusion criteria. A total of 2,330 patients (13.9%) were screened for HCV, and 35 (1.5%) tested positive. Only 42% of patients with exposure-type HCV risk factors, such as HIV infection, injection drug use, hemodialysis, or hemophilia, were screened. Birth after 1965, Asian race, HCV risk factors, and anticipated rituximab therapy were significant predictors of HCV screening; black patients and patients with solid tumors were significantly less likely to be screened. The only significant predictor of a positive anti-HCV result was birth during 1945 to 1965. CONCLUSION: HCV screening rates were low, even among patients with risk factors, and the groups with the highest rates of screening did not match the groups with the highest rates of a positive test result. Misconceptions may exist about which patients should be screened for HCV infection.

Factors associated with survival after opioid rotation in cancer patients presenting to an outpatient supportive care center.

CONTEXT: Data on cancer outpatients undergoing opioid rotation (OR) are limited. Understanding the characteristics of patients who do not follow up after OR could facilitate optimization of OR. OBJECTIVES: To compare the characteristics and overall survival of patients with and without follow-up after OR. METHODS: In this preliminary ad hoc analysis, we reviewed consecutive patients who presented to our supportive care center in 2008 for OR. Data about demographics, scores on the Edmonton Symptom Assessment System and Memorial Delirium Assessment Scale (MDAS), opioid use, and indications for OR were collected. Univariate logistic regression models were used to determine the factors associated with follow-up. Kaplan-Meier curves were used to evaluate survival. RESULTS: Of the 190 patients who underwent OR, 120 (63%) had a follow-up visit. Follow-up visits occurred more frequently in patients with localized disease (89%; 24/27; P = 0.0023), history of substance abuse (100%; 12/12; P = 0.0085), performance status ≤ 2 (66%; 97/146; P = 0.0002), no delirium (67%; 118/177; P = 0.002), and uncontrolled pain as reason for OR (66%; 97/146; P = 0.036). Patients who underwent OR for opioid-induced neurotoxicity (44%; 15/34; P = 0.01) and had higher MDAS scores (P = 0.0009) were less likely to follow up. Both follow-up after OR (P < 0.001) and successful OR (P = 0.012) were associated with longer overall survival, with a difference in median survival of 4.3 and 3 months, respectively. CONCLUSION: Our preliminary study suggests that patients with advanced cancer, poorer performance status, opioid-induced neurotoxicity, and higher MDAS scores are less likely to follow up after OR and may have shorter overall survival and, therefore, require closer follow-up. Patients with unsuccessful OR also may have a shorter overall survival. Further studies are warranted.

Infrequent chemoradiation-induced acute esophagitis in the Asian population: A meta-analysis of published clinical trials for unresectable stage III non-small cell lung cancer.

Severe (grade 3 or higher) esophagitis is one of the major toxicities for chemoradiation in the treatment of stage III non-small cell lung cancer (NSCLC). The difference among ethnic groups has never been investigated in detail. Prospective trials with concurrent platinum-containing chemoradiation in unresectable disease were investigated, and a total of 116 treatment arms with 7520 patients were identified. Univariate analysis demonstrated that treatment arms conducted in Asia had significantly lower incidence of severe esophagitis (170/2534, 6.7%, odds ratio 0.289) than in other nations (1025/4986, 20.6%). In the multivariable model, Asian/non-Asian ethnicity, multi-/single-agent, and split are jointly significant predictors after adjusting for all possible factors. This study suggests that severe esophagitis occurs less frequently in the Asian population compared to the non-Asian population.

Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in philadelphia chromosome-positive acute lymphoblastic leukemia.

The presence of the Philadelphia chromosome in patients with acute lymphoblastic leukemia (Ph(+)ALL) is a negative prognostic indicator. Tyrosine kinase inhibitors (TKI) that target BCR/ABL, such as imatinib, have improved treatment of Ph(+)ALL and are generally incorporated into induction regimens. This approach has improved clinical responses, but molecular remissions are seen in less than 50% of patients leaving few treatment options in the event of relapse. Thus, identification of additional targets for therapeutic intervention has potential to improve outcomes for Ph+ALL. The human epidermal growth factor receptor 2 (ErbB2) is expressed in ~30% of B-ALLs, and numerous small molecule inhibitors are available to prevent its activation. We analyzed a cohort of 129 ALL patient samples using reverse phase protein array (RPPA) with ErbB2 and phospho-ErbB2 antibodies and found that activity of ErbB2 was elevated in 56% of Ph(+)ALL as compared to just 4.8% of Ph(-)ALL. In two human Ph+ALL cell lines, inhibition of ErbB kinase activity with canertinib resulted in a dose-dependent decrease in the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389 (by 60% in Z119 and 39% in Z181 cells at 3 µM). Downstream, phosphorylation of S6-kinase was also diminished in both cell lines in a dose-dependent manner (by 91% in both cell lines at 3 µM). Canertinib treatment increased expression of the pro-apoptotic protein Bim by as much as 144% in Z119 cells and 49% in Z181 cells, and further produced caspase-3 activation and consequent apoptotic cell death. Both canertinib and the FDA-approved ErbB1/2-directed TKI lapatinib abrogated proliferation and increased sensitivity to BCR/ABL-directed TKIs at clinically relevant doses. Our results suggest that ErbB signaling is an additional molecular target in Ph(+)ALL and encourage the development of clinical strategies combining ErbB and BCR/ABL kinase inhibitors for this subset of ALL patients.

Mentoring in pediatric oncology: a report from the Children's Oncology Group Young Investigator Committee.

A formal Mentorship Program within the Children's Oncology Group (COG) was established to pair young investigators (mentees) with established COG members (mentors). Despite the American Academy of Pediatrics policy statement promoting mentorship programs, there are no publications describing and evaluating national mentorship programs in pediatric subspecialties. In this study, a series of internal program evaluations were performed using surveys of both mentors and mentees. Responses were deidentified and analyzed to determine the utility of the program by both participant satisfaction and self-reported academic productivity. Results indicated that mentees were generally satisfied with the program. Mentor-mentee pairs that met at least quarterly demonstrated greater academic productivity than pairings that met less frequently. This formal mentorship program appeared to have subjective and objective utility for the development of academic pediatric subspecialists.

Rasburicase in tumor lysis syndrome of the adult: a systematic review and meta-analysis.

BACKGROUND: The use of rasburicase has been evaluated extensively in children, but not in adults. We review the current literature to evaluate its effect on adults. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adults receiving rasburicase for tumor lysis syndrome (TLS). SELECTION CRITERIA FOR STUDIES: Electronic databases, regulatory documents, and websites were searched up to August 7, 2012. Reference lists of published articles were examined for additional relevant references. Any controlled trial or observational studies (controlled before and after) were included. Studies considering children only or mixing data for children and adults were excluded. INTERVENTION: Rasburicase for TLS. OUTCOMES: The primary outcome was TLS development. Secondary outcomes included percentage of patients improving, total adverse events, acute kidney failure, deaths, and serum uric acid and creatinine levels. RESULTS: 21 studies (24 publications) reported data for 1,261 adult patients, 768 receiving rasburicase for either the treatment or prophylaxis of TLS; these comprised 4 controlled trials and 17 observational studies. No statistically significant differences in clinical TLS development were observed in the controlled trials between the rasburicase and control groups. For the observational studies, 7.4% of patients developed clinical TLS after rasburicase (95% CI, 1.7%-16.7%), 93.4% of patients achieved normalized serum uric acid levels after rasburicase treatment (95% CI, 91.7%-94.6%), 4.4% developed acute kidney injury (95% CI, 3.0%-6.0%), and 2.6% died (95% CI, 0.95%-5.0%). The mean reduction in serum uric acid levels ranged from 5.3-12.8 mg/dL, and for serum creatinine levels, from 0.10-2.1 mg/dL. LIMITATIONS: Controlled trials differed in outcomes reported; meta-analysis was not performed. CONCLUSIONS: Rasburicase is effective in reducing serum uric acid levels in adults with TLS but at a significant cost, and evidence currently is lacking in adults to report whether rasburicase use improves clinical outcomes compared with other alternatives. Until new evidence is available, use of rasburicase may be limited to adult patients with a high risk of TLS.

Case control study of women treated with chemotherapy for breast cancer during pregnancy as compared with nonpregnant patients with breast cancer.

BACKGROUND: The purpose of this analysis was to compare disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) between pregnant and nonpregnant patients with breast cancer. METHODS: From 1989 to 2009, 75 women were treated with chemotherapy during pregnancy. Each pregnant case was matched on age and cancer stage to two nonpregnant patients with breast cancer (controls). Fisher's exact test, the Kaplan-Meier method, and Cox proportional hazards regression models were used. RESULTS: Median follow-up time for patients who were alive at the end of follow-up (n = 159) was 4.20 years (range: 0.28-19.94 years). DFS at 5 years was 72% (95% confidence interval [CI]: 58.3%-82.1%) for pregnant patients and 57% (95% CI: 46.7%-65.8%) for controls (p = .0115). Five-year PFS was 70% (95% CI: 56.8%-80.3%) for pregnant patients and 59% (95% CI: 49.1%-67.5%) for controls (p = .0252). Five-year OS was 77% (95% CI: 63.9%-86.4%) for pregnant patients and 71% (95% CI: 61.1%-78.3%) for controls (p = .0461). Hazard ratio estimates favored improved survival for pregnant patients in univariate analyses and multivariate analyses, controlling for age, year of diagnosis, stage, and tumor grade. CONCLUSIONS: For patients who received chemotherapy during pregnancy, survival was comparable to-if not better than-that of nonpregnant women. Pregnant patients with breast cancer should receive appropriate local and systemic therapy for breast cancer.

A prospective study of family conferences: effects of patient presence on emotional expression and end-of-life discussions.

CONTEXT: Limited research has taken place examining family conferences (FCs) with patients with advanced cancer and their caregivers in the palliative care setting. OBJECTIVES: To characterize the FCs involving cancer patients in a palliative care unit at a comprehensive cancer center and examine the effects of patient participation on emotional expression by the participants and end-of-life discussions. METHODS: A data collection sheet was completed immediately after 140 consecutive FCs that documented the number of participants, caregiver demographics, expressions of emotional distress, dissatisfaction with care, and the topics discussed. Patient demographics and discharge disposition also were collected. RESULTS: Seventy (50%) patients were female, 64 (46%) were white, and 127 (91%) had solid tumors. Median age of patients was 59 years. Patients participated in 68 of 140 FCs (49%). Primary caregivers (n = 140) were female (66%), white (49%), and the spouse/partner (59%). Patients verbalized distress frequently (73%). Primary caregivers' verbal expression of emotional distress was high (82%) but not significantly affected by patient presence (82% vs. 82%, P = 0.936). Verbal expressions of emotional distress by other family members were more common when patients were absent (87%) than when present (73%), P = 0.037. Questions concerning advance directives (21%), symptoms anticipated at death (31%), and caregiver well-being (29%) were infrequent. Patient presence was significantly associated with increased discussions regarding goals of care (P = 0.009) and decreased communication concerning prognosis (P = 0.004) and what symptoms dying patients may experience (P < 0.001). CONCLUSION: There was a high frequency of expression of emotional distress by patients and family members in FCs. Patient participation was significantly associated with decreased verbal emotional expression by family members but not the primary caregiver and was associated with fewer discussions regarding prognosis and what dying patients may experience.

Characteristics of advanced cancer patients with cancer-related fatigue enrolled in clinical trials and patients referred to outpatient palliative care clinics.

CONTEXT: Limited published data exist on whether characteristics of patients with advanced cancer enrolled in cancer-related fatigue clinical trials (CCTs) differ from patients in outpatient palliative care clinics (OPCs). OBJECTIVES: The primary aim of this study was to compare the characteristics of two groups of patients with advanced cancer and moderate-to-severe fatigue: patients in CCTs and patients at an OPC. METHODS: We retrospectively reviewed the records of 337 patients who were enrolled in one of five CCTs for advanced cancer patients at The University of Texas M. D. Anderson Cancer Center as well as the records of 1896 consecutive patients who were referred to our OPC from January 2003 through December 2010. Patients with fatigue scores of ≥4/10 (measured by the Edmonton Symptom Assessment System [ESAS]) were eligible (1252 OPC patients and 337 CCT patients). Patient characteristics, ESAS scores, and survival times were compared using Chi-square tests, Wilcoxon rank sum tests, and the Kaplan-Meier method. RESULTS: Compared with the CCT patients, OPC patients were more likely to be older (58 vs. 59 years; P=0.009) and male (38% vs. 52%; P<0.001). The most common primary cancer type was breast cancer (22%) in the CCT patients and lung cancer (23%) in the OPC patients (P<0.001). The median ESAS scores in the OPC and CCT groups, respectively, were 6 and 4 for pain (P<0.001), 7 and 7 for fatigue (P=0.525), 3 and 2 for depression (P=0.004), 3 and 2 for anxiety (P<0.001), 3 and 2 for dyspnea (P<0.001), and 43 and 32 for the symptom distress score (P<0.001). The median overall survival times were 17.9 months (95% CI 13.5-22.3 months) in the CCT group and 3.8 months (95% CI 3.5-4.1 months) in the OPC group (P<0.001). CONCLUSION: Baseline characteristics and overall survival times significantly differed between patients enrolled in the CCT and OPC groups. Therefore, we conclude that the results of CCTs cannot be generalized to patients being treated in OPCs.

Frequency, outcome, and predictors of success within 6 weeks of an opioid rotation among outpatients with cancer receiving strong opioids.

BACKGROUND: Opioid rotation is used to treat uncontrolled pain and/or opioid-related adverse effects. Our aim was to determine the frequency, indications, outcomes, and predictors of successful opioid rotation in outpatients with cancer. METHODS: Medical records of consecutive outpatients with cancer who received strong opioids and returned for follow-up visit within ≤6 weeks to our supportive care center from January to December 2008 were reviewed. Data on patient characteristics, symptoms, opioid use, indications for opioid rotation, outcomes, and morphine equivalent daily dose were collected. Successful opioid rotation was defined as a two-point or 30% reduction in the symptom score or the resolution of opioid-induced neurotoxicity and continuation of the new opioid at follow-up. RESULTS: Opioid rotation was performed in 120 of 385 patients (31%). The median patient age was 55 years. There were 6/120 patients with missing data. Of the 114 evaluable patients, 68 (60%) were men, 81 (71%) were white, 27 (24%) had gastrointestinal cancer, and 90 (80%) had advanced-stage disease. The median Eastern Cooperative Oncology Group score was 1 (interquartile range: 1-2) and the median time between opioid rotation and follow-up was 14 days (interquartile range: 7-21 days). The most common indications for opioid rotation were uncontrolled pain (95/114; 83%) and opioid-induced neurotoxicity (13/114; 12%). A total of 35 patients (31%) had partial opioid rotation. The median improvements in pain and symptom distress score were -2 (interquartile range: -4 to 0; p < .001) and -5 (interquartile range: -14 to 7; p = .004), respectively. The morphine equivalent daily dose did not change significantly after opioid rotation (p = .156). A total of 65% of patients (74/114) had successful opioid rotation. There were no clinically significant independent predictors for successful opioid rotation. CONCLUSION: Opioid rotation was conducted in 31% of outpatients with cancer, with a 65% success rate. The most frequent reason for opioid rotation was uncontrolled pain. There were no independent predictors for successful opioid rotation.

The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer.

INTRODUCTION: Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes. OBJECTIVES: To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m(2). METHODS: Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Black's nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC. RESULTS: BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue. CONCLUSIONS: Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.

Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy.

Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches.

Cervical spine radiographs in patients with rheumatoid arthritis undergoing anesthesia.

BACKGROUND: There is no consensus on the role of preoperative cervical spine radiographs to screen for instability in patients with rheumatoid arthritis (RA). OBJECTIVES: This study aimed to evaluate the preoperative use of cervical spine radiographs in patients with RA undergoing preoperative anesthesia assessment and to determine whether preoperative radiographic findings influenced anesthesia delivery techniques. METHODS: We reviewed all medical records of RA patients who underwent surgical procedures requiring general anesthesia with airway intubation or monitored anesthesia care without airway intubation. We examined cervical spine radiographs obtained up to 2 years before surgery and determined airway management techniques used during surgery. RESULTS: Overall, 215 patients with RA underwent 217 individual surgeries requiring anesthesia; of these, 176 (82%) underwent general anesthesia with airway management with direct laryngoscopy in 83%, fiber-optic intubation in 10%, and laryngeal mask in 7%. Ninety-two (52%) of the patients receiving airway management had radiographs available for cervical spine evaluation; of these, only 7 (8%) had complete radiographic examinations with which to evaluate possible atlantoaxial subluxation. Eighteen (20%) of the 92 patients receiving airway management had radiographic evidence of cervical spine abnormality. Multiple regression models were conducted to evaluate the association of patient demographics and airway management technique used and showed that the use of fiber-optic intubation or laryngeal mask was not influenced by radiographic results. A difficult oropharyngeal class/glottic visualization grade (3 or 4) as determined by the anesthesiologist was the only statistically significant predictor of fiber-optic intubation or laryngeal mask use. CONCLUSIONS: Cervical spine abnormalities were frequently noted in patients who underwent general surgery but did not influence the choice of airway management. Future prospective studies evaluating the utility of cervical spine radiographs in patients with RA and practice guidelines are needed to ensure appropriate and cost-effective perioperative cervical evaluation and management of patients with RA.

Feasibility, reliability, and validity of the Pediatric Quality of Life Inventory ™ generic core scales, cancer module, and multidimensional fatigue scale in long-term adult survivors of pediatric cancer.

BACKGROUND: Most health-related quality of life assessments are designed for either children or adults and have not been evaluated for adolescent and young adult survivors of pediatric cancer. The objective of this study was to examine the feasibility, reliability, and validity of the Pediatric Quality of Life Inventory (PedsQL ™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale in adult survivors of pediatric cancer. METHODS: Adult survivors (n = 64; Mean age 35 year old; >2 years after treatment) completed the PedsQL™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale. Feasibility was examined with floor and ceiling effects; and internal consistency was determined by Cronbach's coefficient alpha calculations. Inter-factor correlations were also assessed. RESULTS: Significant ceiling effects were observed for the scales of social function, nausea, procedural anxiety, treatment anxiety, and communication. Internal consistency for all subscales was within the recommended ranges (α ≥ 0.70). Moderate to strong correlations between most Cancer Module and Generic Core Scales (r = 0.25 to r = 0.76) and between the Multidimensional Fatigue Scale and Generic Core Scales (r = 0.37 to r = 0.73). CONCLUSIONS: The PedsQL™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale appear to be feasible for an older population of pediatric cancer survivors; however, some of the Cancer Module Scales (nausea, procedural/treatment anxiety, and communication) were deemed not relevant for long-term survivors. More information is needed to determine whether the issues addressed by these modules are meaningful to long-term adult survivors of pediatric cancers.

Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors.

PURPOSE: We evaluated whether patients with human epidermal growth factor receptor 2 (HER2) -positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors. PATIENTS AND METHODS: We retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review. RESULTS: We included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio [HR], 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies. CONCLUSION: We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy.

Retrospective analysis of antitumor effects of zoledronic acid in breast cancer patients with bone-only metastases.

BACKGROUND: Bisphosphonates have been used successfully in the treatment of hypercalcemia and to reduce skeletal complications of bone metastasis, but have not been shown to prevent bone metastasis or to prolong survival time in metastatic breast cancer patients. The aim of this study was to determine whether the progression-free survival (PFS) and overall survival (OS) of patients with bone-only breast cancer metastasis differed based on whether patients received zoledronic acid, pamidronate, or no bisphosphonate upon diagnosis of their metastases. PATIENTS AND METHODS: We retrospectively identified 314 patients diagnosed with bone-only metastasis at the time of initial staging or who developed bone metastasis as the first recurrence site during follow-up from January 1, 1997 to December 31, 2008, at The MD Anderson Cancer Center. Univariate and multivariate Cox hazards models were used to assess the effects of each treatment on PFS and OS. RESULTS: Patients who had more than 1 bone metastasis and Eastern Cooperative Oncology Group (ECOG) performance status of 2 and 3 were more likely to receive zoledronic acid in this analysis. Compared with no bisphosphonate use, the use of zoledronic acid was not significantly associated with longer PFS (hazard ratio [HR] = 0.72, P = .058 in univariate analysis, and HR = 0.80, P = .235 in multivariate analysis) nor with longer OS (HR = 1.04, P = .863 in univariate analysis and HR = 1.34, P = .192 in multivariate analysis). CONCLUSION: Our study demonstrates that for patients with bone-only metastases, zoledronic acid did not prolong PFS or OS. In patients with bone-only metastasis, we could not demonstrate antitumor effects of zoledronic acid.

Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia.

BACKGROUND: Several studies have demonstrated the prognostic utility of absolute lymphocyte count (ALC) during therapy for a range of malignancies, with low ALC associated with adverse outcome. Here we investigated whether ALC retained independent prognostic significance with respect to minimal residual disease (MRD) status in children with acute lymphoblastic leukemia (ALL). PROCEDURE: We reviewed 171 cases of pediatric ALL treated on the Children's Oncology Group P9900 series of treatment trials. Variables analyzed included ALC at several time points during Induction, age at diagnosis, cytogenetics, initial white blood cell count, and MRD status at Day 29 of Induction (MRD-29). RESULTS: We found high ALC at Induction Day 29 (ALC-29) to be an independent, clinically significant predictor of improved relapse-free and overall survival (OS). Patients with ALC-29 >1,500 cells/µl had a superior 6-year relapse-free survival (80 ± 4% vs. 62 ± 8%, P = 0.018) and overall survival (96 ± 2% vs. 74 ± 8%, P = 0.001). Moreover, ALC-29 identified distinct prognostic subgroups within cases stratified by MRD-29. In subjects with >0.01% MRD, ALC-29 > or <1,500 cells/µl had a significant 51% difference in 6-year OS (92 ± 7% vs. 41 ± 16%, P = 0.0001). CONCLUSIONS: ALC, a readily obtainable test, constitutes a significant and independent prognostic factor in childhood ALL that may refine current MRD-based risk stratification algorithms and provide key prognostic information in settings where MRD determination is not feasible.