Cancer by Sfakianakis Alexandros: 02/03/18

Σάββατο 3 Φεβρουαρίου 2018

Obesity surgery and risk of colorectal and other obesity-related cancers: An English population-based cohort study

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Ariadni Aravani, Amy Downing, James D. Thomas, Jesper Lagergren, Eva J.A. Morris, Mark A. Hull
BackgroundThe association between obesity surgery (OS) and cancer risk remains unclear. We investigated this association across the English National Health Service. A population-based Swedish study has previously suggested that OS may increase the risk of developing colorectal cancer (CRC).MethodsA retrospective observational study of individuals who underwent OS (surgery cohort) or diagnosed with obesity, but had no OS (no-surgery cohort) (1997–2013) were identified using Hospital Episode Statistics. Subsequent diagnosis of CRC, breast, endometrial, kidney and lung cancer, as well as time 'at risk', were determined by linkage to National Cancer Registration & Analysis Service and Office of National Statistics data, respectively. Standardised incidence ratios (SIR) in relation to OS were calculated.Results1 002 607 obese patients were identified, of whom 3.9% (n = 39 747) underwent OS. In the no-surgery obese population, 3 237 developed CRC (SIR 1.12 [95% CI 1.08–1.16]). In those who underwent OS, 43 developed CRC (SIR 1.26 [95% CI 0.92–1.71]). The OS cohort demonstrated decreased breast cancer risk (SIR 0.76 [95% CI 0.62–0.92]), unlike the no surgery cohort (SIR 1.08 [95% CI 1.04–1.11]). Increased risk of endometrial and kidney cancer was observed in surgery and no-surgery cohorts.ConclusionsCRC risk is increased in individuals diagnosed as obese. Prior obesity surgery was not associated with an increased CRC risk. However, the OS population was small, with limited follow-up. Risk of breast cancer after OS is reduced compared with the obese no-surgery population, while the risk of endometrial and kidney cancers remained elevated after OS.

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Obesity surgery and risk of colorectal and other obesity-related cancers: An English population-based cohort study

Abscopal effects with hypofractionated schedules extending into the effector phase of the tumor-specific T cell response

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Xuanwei Zhang, Gabriele Niedermann
PurposeHypofractionated radiotherapy (hRT) combined with immune checkpoint blockade (ICB) can induce T cell-mediated local and abscopal antitumor effects. We previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between day 5 and day 8 after hRT; since TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses in combination with anti-PD1 antibody treatment.Materials and MethodsIn mice bearing two B16-CD133 melanoma tumors, the primary was irradiated with 3 × 9.18 Gy in 3 or 5 days, or with 5 × 6.43 Gy in 10 days; anti-PD1 antibody was given weekly. Mice were followed for tumor growth and survival. T cell responses were determined on days 8 and 15 of treatment. The role of regional lymph nodes was studied by administering FTY720, which blocks lymph node egress of activated T cells. Tumor growth measurements following combination treatment based on short or extended hRT and control treatments were also performed in the wild-type B16 melanoma and 4T1 breast carcinoma models.ResultsIn the B16-CD133 model, growth inhibition of irradiated primary and non-irradiated secondary tumors and overall survival were similar with all three hRT/anti-PD1 combinations, superior to hRT or anti-PD1 monotherapy, and depended strongly on CD8+ T cells. TIL infiltration and local and systemic tumor-specific CD8+ T cell responses were also similar, regardless of whether short or extended hRT was used. Administration of FTY720 accelerated growth of both primary and secondary tumors, strongly reduced their TIL infiltration and increased tumor-specific CD8+ T cells in the lymph nodes draining the irradiated tumor. In the 4T1 model, local and abscopal tumor control were also similar regardless of whether short or extended hRT was used, although the synergy between hRT and anti-PD1 was weaker. No synergies were found in the B16 wild-type model lacking an exogenous antigen.ConclusionsOur data suggest that combination therapy with hRT schedules extending into the period during which treatment-induced T cells infiltrate the irradiated tumor can provoke similar local and systemic antitumor effects as therapy based on shorter schedules, if regional lymph nodes supply sufficient tumor-specific T cells. This has implications for planning clinical RT/ICB trials.

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STING-dependent interferon-λ1 induction in HT29 cells, a human colorectal cancer cell line following gamma-radiation

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jianzhou Chen, Bostjan Markelc, Jakob Kaeppler, Vivian M.L. Ogundipe, Yunhong Cao, W. Gillies McKenna, Ruth J. Muschel
PurposeIonizing radiation augments anti-tumor immune responses with interferons (IFN) acting as mediators. Of the three types of IFNs, type I and II IFNs are induced in irradiated tumors with induction of type III IFNs (IFNLs) currently not reported. Here, we investigated the induction of type III IFNs in human cancer cells by gamma-rays and its mechanisms.Methods and MaterialsType III IFN expression in human cancer cell lines following gamma-ray irradiation in vitro was assessed by RT-qPCR and ELISA. Signaling pathways mediating type III IFN induction were examined by a variety of means, including immunoblotting, flow cytometry, confocal imaging and RT-qPCR. Key mediators in these pathways were further explored and validated using gene CRISPR knockout or shRNA knockdown.ResultsExposure to gamma-rays directly induced type III IFNs (mainly IFNL1) in human cancer cell lines in dose- and time-dependent fashions. The induction of IFNL1 was primarily mediated by the cytosolic DNA sensors-STING-TBK1-IRF1 signaling axis with a lesser contribution from NF-κB signaling in HT29 cells. In addition, type III IFN signaling through its receptors serves as a positive feedback loop further enhancing IFN expression via upregulation of the kinases in the STING-TBK1 signaling axis.ConclusionsOur results suggest that IFNL1 can be upregulated in human cancer cell lines following gamma-rays treatment. In HT29 cells this induction occurs via the STING pathway adding another layer of complexity to the understanding of radiation-induced anti-tumor immunity and may provide novel insights into IFN-based cancer treatment.

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Ki67 is an independent predictor of recurrence in the largest randomised trial of 3 radiation fractionation schedules in localised prostate cancer

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Anna C. Wilkins, Barry Gusterson, Zsolt Szijgyarto, Joanne Haviland, Clare Griffin, Christine Stuttle, Frances Daley, Catherine M. Corbishley, David P. Dearnaley, Emma Hall, Navita Somaiah
BackgroundExternal beam radiotherapy is delivered using a uniform fractionation schedule for localised prostate tumours, individualising fractionation according to tumour biology could improve outcomes. Additionally recurrence rates following radiotherapy vary considerably, better prognostic markers could improve treatment stratification. This study assessed if the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiotherapy fractionation in patients participating in ", a randomised trial of three radiotherapy fractionation schedules (74Gy/37f vs 60Gy/20f vs 57Gy/19f).MethodsA matched case:control study design was used, patients with biochemical/clinical failure >2 years after radiotherapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors (Gleason score, PSA, tumour-stage) and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker-fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation.ResultsUsing 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6% (IQR:3.9-9.8) and 11.0% (IQR:7.0-15.0) respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR was estimated to increase by 9% per 1% increase in mean Ki67 score (OR=1.09, 95%CI:1.04–1.15,p=0.001). Interaction terms between Ki67 and fractionation schedules were not statistically significant.ConclusionsDiagnostic Ki67 did not predict BCR according to fractionation schedule in ", however it was a strong independent prognostic factor for BCR.

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Relationship Between Citation-Based Scholarly Activity of United States Radiation Oncology Residents and Subsequent Choice of Academic versus Private Practice Career

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shearwood McClelland, Timur Mitin, Lynn D. Wilson, Charles R. Thomas, Jerry J. Jaboin
IntroductionCitation-based scholarly activity of physicians has become increasingly evaluated via the Hirsch index (h-index), which assesses the number of manuscripts (h) cited at least h times. However, such evaluation involving Radiation Oncology residents is lacking in the peer-reviewed literature. The objective of this study was to assess h-index data and its association with resident choice of academic versus private practice career.MethodsA list of 2016 radiation oncology resident graduates (163 residents from 76 Accreditation Council for Graduate Medical Education-certified programs) and their post-residency career choice (academic versus private practice) was compiled as previously described (McClelland et al., Practical Radiation Oncology 2017). The SCOPUS bibliometric citation database was then searched to collect h-index data for each resident. Demographics included in analyses were gender and PhD degree status.ResultsMean h-index score for all resident graduates was 4.15. Residents with a PhD had significantly higher h-index scores (6.75 versus 3.42; p<0.01), while there was no statistically significant difference in h-index scores between male and female residents (4.38 versus 3.36; p=0.06). With regard to career choice, residents choosing academic careers had higher h-index scores than those choosing private practice (5.41 versus 2.96; p<0.01). There was no significant difference in mean h-index scores between male and female residents regardless of private practice (3.15 versus 2.19; p=0.25) or academic (5.80 versus 4.30; p=0.13) career choice.ConclusionThe average radiation oncology resident graduate published a minimum of four manuscripts cited at least four times. Graduates with a PhD are significantly more likely to have higher h-index scores, as are residents who choose academic over private practice careers. There is no significant difference in h-index score between male and female residents regardless of career choice. These results offer up-to-date benchmarks for evaluating radiation oncology resident productivity and have potential utility in predicting career choices post-residency.

Teaser

The average radiation oncology resident graduate published a minimum of four manuscripts cited at least four times. Graduates with a PhD are significantly more likely to have higher h-index scores, as are residents who choose academic over private practice careers. There is no significant difference in h-index score between male and female residents regardless of career choice. These results offer up-to-date benchmarks for evaluating resident productivity and have potential utility in predicting career choices post-residency.

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Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-Analysis of Propensity Score Studies

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hanbo Chen, Joanna M. Laba, R. Gabriel Boldt, Christopher D. Goodman, David A. Palma, Suresh Senan, Alexander V. Louie
BackgroundAs no completed randomized trials of surgery versus stereotactic ablative radiotherapy (SABR) in patients with early-stage non-small cell lung cancer are available, numerous propensity score studies have attempted to mimic the setting of clinical trials using non-randomized data. We performed a meta-analysis of propensity score studies comparing SABR and surgery.MethodsThe Medline and Embase databases were queried up to December 2016. Two authors independently reviewed the records for inclusion and extracted outcome measures. The study was conducted according to PRISMA and MOOSE guidelines. Primary meta-analysis and secondary analyses were carried out using R (v3.3.2) at a significance level of 0.05.ResultsSixteen studies were included in the meta-analysis. Overall survival favored surgery (SABR versus surgery hazard ratio = 1.48 [95% confidence interval: 1.26-1.72], I² = 80.5%). Lung cancer-specific survival was not significantly different between SABR and surgery (hazard ratio = 1.17 [0.92-1.50], I² = 18.6%). On stratification, overall survival favored both lobectomy and sublobar resection over SABR, though lung cancer-specific survival was again not significantly different. On secondary analysis, lymph node upstaging rate was 15.6% following surgery, with 11.4% of patients receiving chemotherapy. Propensity score-matching caliper distance and first author specialty was found to be associated with survival endpoints on regression.ConclusionsFor patients with early stage non-small cell lung cancer who are eligible for either treatment, better overall survivals were seen after surgery compared to SABR. However, lung cancer-specific survival was similar for both treatments. Prospective clinical trials are preferred to propensity analyses in evaluating the nature of non-cancer related mortality post-SABR.

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Abscopal effects with hypofractionated schedules extending into the effector phase of the tumor-specific T cell response

STING-dependent interferon-λ1 induction in HT29 cells, a human colorectal cancer cell line following gamma-radiation

Ki67 is an independent predictor of recurrence in the largest randomised trial of 3 radiation fractionation schedules in localised prostate cancer

Relationship Between Citation-Based Scholarly Activity of United States Radiation Oncology Residents and Subsequent Choice of Academic versus Private Practice Career

Teaser

Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-Analysis of Propensity Score Studies

Development of the “Day 100 Talk”: Addressing existing communication gaps during the early cancer treatment period in childhood cancer

Abstract

Background

Families' communication needs during the early cancer treatment period (ECTP) may not be optimally met by current practices. We sought to identify potential communication gaps and to ameliorate these by developing a novel in-depth conversation between families and their pediatric oncologists, the "Day 100 Talk" (D100), during the ECTP.

Procedure

We conducted semistructured interviews with parents and patients undergoing childhood cancer treatment for < 7 months. Interviews sought to elicit perceived communication gaps regarding cancer care and inform D100 development. Following qualitative analysis of interview responses, we developed a three-part D100 conversation tool consisting of a preparatory family worksheet, a conversation guide, and a family summary sheet. We presented the tool during interviews and a focus group with pediatric oncology providers and revised it to incorporate provider input.

Results

Twenty-two stakeholders (six parents, five adolescents, and 11 providers) participated in interviews or a focus group. Parents and patients perceived insufficient anticipatory guidance as the most important communication gap. They also reported sometimes withholding worries and cancer-related beliefs. Meanwhile, oncology providers worried about "opening Pandora's Box" and limited clinical time. Additionally, providers reported employing indirect methods such as surmising to determine families' needs and relying on psychosocial clinicians to engage families around potentially "taboo" issues of emotional coping and spirituality.

Conclusion

Creating a communication occasion (D100), ensuring complementary disciplinary expertise through joint participation by oncologists and psychosocial clinicians, and providing a conversation tool to prompt disclosure by families and facilitate anticipatory guidance may ameliorate existing communication gaps during the ECTP.

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A novel frameshift mutation in the MPL gene in congenital amegakaryocytic thrombocytopenia

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The ASPHO 2018 Distinguished Career Award goes to Dr. Michael P. Link

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Pazopanib therapy for desmoid tumors in adolescent and young adult patients

Abstract

Background

Desmoid tumors/aggressive fibromatosis (DT/AF) lack a reliably effective medical therapy. Surgical resection may be morbid and does not preclude recurrence. Radiation may carry severe late effects, particularly detrimental in young patients. At our institution, we recently observed promising results with pazopanib therapy for DT/AF in adolescent and young adult (AYA) patients.

Procedure

Retrospective single-institution chart review.

Results

Six DT/AF patients of 3–21 years with previously treated DT/AF received pazopanib; 31 DT/AF patients received established therapies only. In both groups, median age at diagnosis was 16 years, female patients comprised 50%, and most common DT/AF site was extremity. Established therapies showed few objective responses and most patients therefore received multiple therapies. Surgical resection had a 68% recurrence rate. Of eight patients who received vinblastine/methotrexate, only one had a partial response (PR) by RECIST 1.1 and five had stable disease (SD); 62.5% required additional therapy. Of seven patients who received sulindac/tamoxifen, none showed objective improvement. In contrast, pazopanib demonstrated best responses by RECIST of PR in two of seven and SD in six of seven tumors. A PR of 66% was observed in a patient who had failed multiple prior therapies. The mesenteric DT/AF also showed PR. Maximum volumetric decrease by T2-weighted magnetic resonance imaging (MRI) was 97%. Dramatically increased fibrosis was seen on T2-weighted MRI. Patients reported pain relief and improvement in function within 1 month. Except for one case of edema, all other toxicities responded to dose reduction without sacrificing objective treatment response.

Conclusion

Pazopanib provides a promising, well-tolerated therapy for DT/AF in the AYA population and warrants further study.

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Possible involvement of IL-6-producing tissue-resident macrophages in early-onset pericardial effusion pathogenesis after hematopoietic stem cell transplantation

Abstract

Purpose

Pericardial effusion (PE) is a potentially life-threatening complication following hematopoietic stem cell transplantation (HCT). A higher incidence of early-onset PE, unrelated to graft-versus-host disease, before day 100 after HCT has been reported in pediatric patients, but the pathogenic mechanism is poorly understood. Aiming to determine the pathogenesis of early-onset PE in pediatric patients, we analyzed the cytokine concentration and cell population in the pericardial fluid of four pediatric patients with PE.

Methods

Between January 2009 and December 2015, four patients requiring pericardiocentesis for clinically significant PE were identified in 60 patients. We evaluated the interleukin-6 (IL-6), interferon-γ, IL-1β, and tumor necrosis factor-α levels in PE. Two patients were available for analysis with intracellular cytokine flow cytometry and a chimerism assay.

Results

All patients showed the accumulation of pericardial macrophages and high concentrations of IL-6 in PE. Notably, the accumulated pericardial macrophages were CD163⁺CD15⁺CD14⁺ cells of host origin that produced IL-6.

Conclusion

These IL-6-producing tissue-resident macrophages may be key players in the pathogenesis of early-onset PE.

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Determining the prevalence of vestibular screening failures in pediatric cancer patients whose therapies include radiation to the head/neck and platin-based therapies: A pilot study

Abstract

Background

Sensorineural hearing loss due to ototoxic cancer therapy is well established; effects on the vestibular system are unknown. We examined the feasibility of implementing vestibular screens for pediatric cancer survivors exposed to ototoxic agents. The prevalence of screening failures is reported.

Methods

Cancer survivors who were 6–17 years, at least 1-month posttreatment, and received ototoxic therapy (radiation to the head/neck, cisplatin, carboplatin) were eligible. Screening measures included (1) Pediatric Vestibular Symptom Questionnaire, (2) Modified Clinical Test of Sensory Interaction on Balance, and (3) Dynamic Visual Acuity.

Results

Vestibular screening failures were observed in 30 participants (60%). Patients with a brain tumor diagnosis were at increased risk for failures compared to nonbrain tumor patients (74.2% vs. 36.8%, P = 0.009). Patients who underwent brain surgery were at increased risk for failures compared to patients without brain surgery (71% vs. 42%, P = 0.043). Patients with a longer duration between end of treatment and vestibular screening had a reduced risk of failures, with an almost 20% decrease for each year between the time points (odds ratio = 0.812; 95% confidence interval: 0.683–0.964, P = 0.018). Receiving carboplatin correlated with a decreased risk of failure (P = 0.016), due to a negative correlation with other clinical risk factors (diagnosis of a brain tumor, major brain surgery) that are associated with vestibular screening failure.

Conclusion

Vestibular screening failures are highly prevalent in childhood cancer survivors who received ototoxic therapy. Broad screening of this population and further characterization of these patients are warranted.

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Noninvasive encapsulated follicular variant of papillary thyroid carcinoma: Should it also be reclassified in children?

Abstract

Background

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (noniEFVPTC) has low risk of adverse outcome in adults, warranting reclassification as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In children, thyroid nodules have higher risk of malignancy and it is unknown if encapsulated FVPTC (EFVPTC) and infiltrative FVPTC (IFVPTC) tumors have different behavior. We analyzed the clinicopathologic features of follicular variant of papillary thyroid carcinoma (FVPTC) subtypes in our pediatric population to determine if noniEFVPTC has an indolent course as reported in adults.

Procedure

We retrospectively studied all patients diagnosed with FVPTC at our institution. The clinicopathologic characteristics of the histologic subtypes were compared.

Results

Eighteen patients were identified, all treated with total thyroidectomy. No significant differences in age, sex, tumor size, focality, or prior malignancy were detected between subtypes. Extrathyroidal extension had significantly higher incidence in IFVPTC (5/8) compared with EFVPTC (1/10, P = 0.03), translating in significantly more T3 tumors within IFVPTC subtype (5/8), whereas most EFVPTC cases had T1 staging (6/10, T1 vs. T3, P = 0.05). EFVPTC had significantly lower rate of lymph node involvement (N1 in 2/8) compared with IFVPTC (N1 in 8/8, P = 0.003). Only one patient diagnosed with IFVPTC developed extranodal recurrence. When noniEFVPTC and iEFVPTC were separately compared, the noninvasive form showed no propensity for invasive growth (T3 staging: 0/4 vs. 2/6), lymph node metastasis (N1: 0/3 vs. 2/5) or extranodal recurrence.

Conclusion

In children, noniEFVPTC/NIFTP has indolent behavior, warranting consideration of less aggressive management, similar to adults.

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Treatment of a pediatric patient with MET-amplified signet ring cell adenocarcinoma of the stomach with crizotinib

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Early outcomes and patterns of failure following proton therapy for nonmetastatic intracranial nongerminomatous germ cell tumors

Abstract

Background

Although dosimetric comparisons demonstrate the advantage of proton therapy (PT) over conventional radiotherapy for nongerminomatous germ cell tumors (NGGCT), clinical outcome data for this rare tumor are lacking. We sought to evaluate outcomes for children with NGGCT treated with PT.

Methods

Between 2007 and 2016, 14 children (median age 11, range, 5–19 years) with nonmetastatic NGGCT were treated with PT after induction chemotherapy. Most (8/14) were mixed germ cell. Five of 14 patients had complete resection of their primary tumor before radiation. Off study, eight patients received 36 Gy (RBE [relative biological effectiveness]) craniospinal irradiation (CSI). On study, two patients received 30.6 Gy (RBE) whole-ventricle irradiation and four received focal radiation alone. All patients received a total dose of 54 Gy (RBE) to the tumor/tumor bed.

Results

At a median follow-up of 2.8 years, all patients were alive with no local recurrences. Three-year progression-free survival was 86%. Both metastatic recurrences occurred in patients treated with focal radiation alone; one with an immature teratoma developed an isolated spinal recurrence 5 months after treatment. Another with a mixed germ cell tumor developed a multifocal ventricular and shunt tract recurrence 7 months after treatment. Serious toxicity was minimal, including cataracts and hormone deficiency, and limited to children who received CSI.

Conclusion

Early outcomes in children treated for NGGCT suggest the high conformality of PT does not compromise disease control and yields low toxicity. This pattern of failure data adds to growing evidence suggesting chemotherapy followed by focal radiotherapy alone is inadequate in controlling localized NGGCT.

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Parent perspectives on information about late effects of childhood cancer treatment and their role in initial treatment decision making

Abstract

Background

Though most childhood cancer survivors experience late effects of treatment, we know little about parent preferences for late effects information during therapy, or how parents weigh late effects when making treatment decisions. Our objective was to explore how parents of children with cancer consider late effects in initial treatment decision making and during active cancer treatment.

Methods

Semistructured interviews were conducted with 12 parents of children with cancer who were actively receiving treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio-recorded, transcribed verbatim, and qualitatively analyzed using thematic analysis.

Results

Ten of 12 parents reported that they had to decide between two or more treatment options for their child's cancer. Of those, 50% (5/10) considered late effects to be an important factor in their decision making. Most parents wanted early and detailed information about their child's risk of late effects to make treatment decisions and to feel prepared for the future. However, a few parents felt too overwhelmed to focus on late effects at diagnosis. While many recalled extensive late effects information in informed consent discussions, some parents felt these issues were minimally addressed.

Conclusion

Parents desire detailed information about late effects to make informed treatment decisions and prepare for the future. Despite the role of late effects in treatment decision making, some parents feel that late effects are either inadequately addressed or too overwhelming to process at diagnosis. Parents may benefit from early assessment of their information needs and a return to these issues over time.

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“How I approach…”—A new series in Pediatric Blood & Cancer

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Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib

Abstract

Efficacy of BRAF V600E targeted therapies in brain tumors harboring the mutation has been shown in several case reports and is currently being studied in larger clinical trials. Monotherapy with vemurafenib has been associated with significant side effects, including rashes, papillomas, and squamous cell carcinomas. Here we describe an adolescent female with anaplastic ganglioglioma and significant skin reaction to vemurafenib with subsequent tumor response and tolerance to the BRAF/MEK inhibitor combination of dabrafenib and trametinib without recurrence of previous reaction.

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Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated with neuroblastoma

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Development of the “Day 100 Talk”: Addressing existing communication gaps during the early cancer treatment period in childhood cancer

Abstract

Background

Procedure

Results

Conclusion

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A novel frameshift mutation in the MPL gene in congenital amegakaryocytic thrombocytopenia

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The ASPHO 2018 Distinguished Career Award goes to Dr. Michael P. Link

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Pazopanib therapy for desmoid tumors in adolescent and young adult patients

Abstract

Background

Procedure

Retrospective single-institution chart review.

Results

Conclusion

Pazopanib provides a promising, well-tolerated therapy for DT/AF in the AYA population and warrants further study.

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Possible involvement of IL-6-producing tissue-resident macrophages in early-onset pericardial effusion pathogenesis after hematopoietic stem cell transplantation

Abstract

Purpose

Methods

Results

Conclusion

These IL-6-producing tissue-resident macrophages may be key players in the pathogenesis of early-onset PE.

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Determining the prevalence of vestibular screening failures in pediatric cancer patients whose therapies include radiation to the head/neck and platin-based therapies: A pilot study

Abstract

Background

Methods

Results

Conclusion

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Noninvasive encapsulated follicular variant of papillary thyroid carcinoma: Should it also be reclassified in children?

Abstract

Background

Procedure

We retrospectively studied all patients diagnosed with FVPTC at our institution. The clinicopathologic characteristics of the histologic subtypes were compared.

Results

Conclusion

In children, noniEFVPTC/NIFTP has indolent behavior, warranting consideration of less aggressive management, similar to adults.

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Treatment of a pediatric patient with MET-amplified signet ring cell adenocarcinoma of the stomach with crizotinib

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Early outcomes and patterns of failure following proton therapy for nonmetastatic intracranial nongerminomatous germ cell tumors

Abstract

Background

Methods

Results

Conclusion

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Parent perspectives on information about late effects of childhood cancer treatment and their role in initial treatment decision making

Abstract

Background

Methods

Results

Conclusion

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“How I approach…”—A new series in Pediatric Blood & Cancer

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Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib

Abstract

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Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated with neuroblastoma

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Ultrasound-guided lumbar puncture in pediatric patients: technical success and safety

Abstract

Background

Disadvantages of fluoroscopically guided lumbar puncture include delivery of ionizing radiation and limited resolution of incompletely ossified posterior elements. Ultrasound (US) allows visualization of critical soft tissues and the cerebrospinal fluid (CSF) space without ionizing radiation.

Objective

To determine the technical success and safety of US-guided lumbar puncture in pediatric patients.

Materials and methods

A retrospective review identified all patients referred to interventional radiology for lumbar puncture between June 2010 and June 2017. Patients who underwent lumbar puncture with fluoroscopic guidance alone were excluded. For the remaining procedures, technical success and procedural complications were assessed. Two hundred and one image-guided lumbar punctures in 161 patients were included. Eighty patients (43%) had previously failed landmark-based attempts.

Results

One hundred ninety-six (97.5%) patients underwent lumbar puncture. Five procedures (2.5%) were not attempted after US assessment, either due to a paucity of CSF or unsafe window for needle placement. Technical success was achieved in 187 (95.4%) of lumbar punctures attempted with US guidance. One hundred seventy-seven (90.3%) were technically successful with US alone (age range: 2 days-15 years, weight range: 1.9-53.1 kg) and an additional 10 (5.1%) were successful with US-guided thecal access and subsequent fluoroscopic confirmation. Three (1.5%) cases were unsuccessful with US guidance but were subsequently successful with fluoroscopic guidance. Of the 80 previously failed landmark-based lumbar punctures, 77 (96.3%) were successful with US guidance alone. There were no reported complications.

Conclusion

US guidance is safe and effective for lumbar punctures and has specific advantages over fluoroscopy in pediatric patients.

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Ultrasound-guided lumbar puncture in pediatric patients: technical success and safety

Abstract

Background

Objective

To determine the technical success and safety of US-guided lumbar puncture in pediatric patients.

Materials and methods

Results

Conclusion

US guidance is safe and effective for lumbar punctures and has specific advantages over fluoroscopy in pediatric patients.

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CREPT overexpression is associated with proliferation behaviors and poor prognosis in non-small cell lung cancer

Summary

The cell-cycle-related and expression-elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non-small cell lung cancer (NSCLC) remains unclear.In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western Blot and RT-PCR. The correlation between CREPT expression and clinical pathologic features was analyzed in 271 NSCLC patients. Prognostic value of CREPT expression was evaluated by Kaplan-Meier analysis and Cox regression analysis. CREPT was overexpressed in Calu-1 cell lines by using plasmid vector and its biological function was explored both in vitro and in vivo. We found that CREPT was significantly overexpressed in NSCLC compared with paired adjacent non-tumor tissues, and the expression level of CREPT was correlated with tumor differentiation, lymph node metastasis and clinical stage. Kaplan-Meier analysis showed that the RFS and OS of high CREPT expression groups were significantly shorter than those of the low CREPT expression group. Multivariate analysis was identified that CREPT might be an independent biomarker for the prediction of NSCLC prognosis. Overexpression of CRPET increased cell proliferation enhanced the migration and invasion ability of Calu-1 cells (a human NSCLC cell line with relative low CRPET expression) in vitro. Moreover, CREPT overexpression promoted tumor growth in nude mice model. These results suggest that CREPT is closely relevant to the proliferation of NSCLC cells and it might be a potential prognostic marker in NSCLC patients.

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CREPT overexpression is associated with proliferation behaviors and poor prognosis in non-small cell lung cancer

Summary

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Development and validation of an MRI-based model to predict response to chemoradiotherapy for rectal cancer

To safely implement organ preserving treatment strategies for patients with rectal cancer, well-considered selection of patients with favourable response is needed. In this study, we develop and validate an MRI-based response predicting model.

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Review of the patient positioning reproducibility in head-and-neck radiotherapy using Statistical Process Control

A remarkable improvement in patient positioning was observed after the implementation of various process changes aiming to increase the consistency of patient positioning throughout the radiotherapy treatment chain. However, no tool was available to describe these changes over time in a standardised way. This study reports on the feasibility of Statistical Process Control (SPC) to highlight changes in patient positioning accuracy and facilitate correlation of these changes with the underlying process changes.

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Update of the systematic review of palliative radiation therapy fractionation for bone metastases

Radiation therapy is an effective modality for pain management of symptomatic bone metastases. We update the previous meta-analyses of randomized trials comparing single fraction to multiple fractions of radiation therapy in patients with uncomplicated bone metastases.

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Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate

Abstract

Background

This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).

Patients and methods

We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis.

Results

IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6 months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P = 0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2 months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P = 0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P = 0.026 and 0.005, respectively) and overall survival (OS) (P = 0.029 and 0.001, respectively).

Conclusion

The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis.

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Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate

Abstract

Background

This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).

Patients and methods

Results

Conclusion

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End-of-life care of children with diffuse intrinsic pontine glioma

Abstract

The end-of-life management of children with diffuse intrinsic pontine glioma (DIPG) is challenging. Families cope with debilitating symptoms and make complex decisions regarding their child's care. However, there is little evidence guiding palliative care provision for these children. Our objective was to describe the dying trajectory of children with DIPG, their symptoms, the care they require and the end-of-life decisions made for them. This retrospective cohort study analyzed the end-of-life care of 41 consecutive patients with DIPG who died between January 2001 and June 2010. All patients died of disease progression, experiencing a significant symptom burden prior to death. Despite this, the majority of patient days at the end of life were spent at home. However, 60% of patients were hospitalized at least once in their final 3 months, often close to the time of death. A wide range of healthcare professionals were involved, providing a range of medicinal/non-medicinal interventions. Chemotherapy was given to 30% of patients in their final month. Thirty of 33 families approached (91%) agreed to a "Do not resuscitate" order. A small subset of families opted for intensive treatment towards the end of life including cardiopulmonary resuscitation, intensive care admission and mechanical ventilation. Children with DIPG have complex needs and require intensive multidisciplinary support. This paper describes the end-of-life choices made for these children and discusses how these choices influence our institutional model for palliative care. We believe this approach will be useful to clinicians caring for similar patients.

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End-of-life care of children with diffuse intrinsic pontine glioma

Abstract

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Somatic NRAS mutation in patient with generalized lymphatic anomaly

Abstract

Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.

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Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling

Abstract

The principal function of glomeruli is to filter blood through a highly specialized filtration barrier consisting of a fenestrated endothelium, the glomerular basement membrane and podocyte foot processes. Previous studies have uncovered a crucial role of endothelial a disintegrin and metalloprotease 10 (ADAM10) and Notch signaling in the development of glomeruli, yet the resulting defects have not been further characterized nor understood in the context of kidney development. Here, we used several different experimental approaches to analyze the kidneys and glomeruli from mice lacking ADAM10 in endothelial cells (A10ΔEC mice). Scanning electron microscopy of glomerular casts demonstrated enlarged vascular diameter and increased intussusceptive events in A10ΔEC glomeruli compared to controls. Consistent with these findings, genes known to regulate vessel caliber (Apln, AplnR and Vegfr3) are significantly upregulated in A10ΔEC glomeruli. Moreover, transmission electron microscopy revealed the persistence of diaphragms in the fenestrae of A10ΔEC glomerular endothelial cells, which was corroborated by the elevated expression of the protein PLVAP/PV-1, an integral component of fenestral diaphragms. Analysis of gross renal vasculature by light sheet microscopy showed no major alteration of the branching pattern, indicating a localized importance of ADAM10 in the glomerular endothelium. Since intussusceptions and fenestrae with diaphragms are normally found in developing, but not mature glomeruli, our results provide the first evidence for a crucial role of endothelial ADAM10, a key regulator of Notch signaling, in promoting the development and maturation of the glomerular vasculature.

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Somatic NRAS mutation in patient with generalized lymphatic anomaly

Abstract

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Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling

Abstract

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EGFR expression in circulating tumor cells from high-grade Metastatic Sarcomas.

EGFR expression in circulating tumor cells from high-grade Metastatic Sarcomas.

Cancer Biol Ther. 2018 Feb 02;:0

Authors: Braun AC, de Mello CAL, Corassa M, Abdallah EA, Urvanegia AC, Alves VS, Troncarelli B, Díaz M, Nicolau UR, Souza E Silva V, Calsavara V, Paterlini-Brechót P, Chinen LTD

Abstract
INTRODUCTION: Soft tissue Sarcomas (STS) are rare malignances, with high mortality rates. Half of patients develop metastasis. The presence of isolated Circulating Tumor Cells (CTCs) and Circulating Tumor Microemboli (CTM) in the blood may be early markers of tumor invasion. EGF family receptors can also influence this process.
OBJECTIVES: to quantify CTCs and identify CTM as well as the EGFR protein expression in these cells and correlate with clinical outcome in metastatic STS.
MATERIALS AND METHODS: Approximately 8mL of blood was prospectively collected from patients with different types of high grade STS, before the beginning of chemotherapy. The samples were processed and filtered by ISET (Rarecells, France) for the isolation and quantification of CTCs and CTMs. EGFR expression was analysed by immunocytochemistry (ICC) on CTCs/ CTMs.
RESULTS: we analyzed 18 patients with median age of 49 years18-77. The median CTCs number was 2.0 CTCs/mL (0-11 CTCs/mL) and CTM were found in 27.7% of patients. The positivity for EGFR in CTCs was observed in 83.3% of the patients. Progression-free survival (PFS) of positive EGFR staining compared to negative EGFR in CTCs was 2.2 months x NR (not reached) (p = 0.117). The PFS of first line patients with EGFR + CTCs was 2.2 months versus NR, for EGFR- CTCs (p = 0.156).
CONCLUSIONS: this is the first study to demonstrate the expression of EGFR protein in CTCs from sarcoma patients. Although our findings had not reach statistical significance, they could open an area for future investigation. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of EGFR in promoting tumor metastasis in sarcoma.

PMID: 29394136 [PubMed - as supplied by publisher]

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MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1.

MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1.

Cancer Biol Ther. 2018 Feb 02;:1-10

Authors: Maolakuerban N, Azhati B, Tusong H, Abula A, Yasheng A, Xireyazidan A

Abstract
In this study, we investigated the mechanism of miR-200c-3p and SLC6A1 in regulating cell activity of clear cell renal cell carcinoma (CCRCC). The mRNA and miRNA expressions of tissue specimens were analyzed by CapitalBio Corporation (Beijing, China). The expression of SLC6A1 in CCRCC cells was examined through qRT-PCR and western blot. The migration and invasion ability of 786-O cells was testified by transwell assay after transfected. 786-O cell proliferation ability was detected by MTT assay. Dual luciferase reporter assay verified the association between SLC6A1 and miR-200c-3p. SLC6A1 was high expressed and miR-200c-3p was low expressed in CCRCC tissues and cells. Besides, lower SLC6A1 expression indicated longer survival time and higher survival rate. MiR-200c-3p could directly target at SLC6A1 and reduce its expression. MiR-200c-3p inhibited the proliferation, migration and invasion in 786-O cells by down-regulating SLC6A1 expression. The results suggested that the miR-200c-3p served as a suppressor for CCRCC via down-regulating SLC6A1.

PMID: 29394133 [PubMed - as supplied by publisher]

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DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a.

DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a.

Cancer Biol Ther. 2018 Feb 02;:0

Authors: Zhou Y, Perez RE, Duan L, Maki CG

Abstract
MDM2 antagonists stabilize and activate wild-type p53, and histone methyltransferase (HMT) inhibitors reduce methylation on histone lysines and arginines. Both MDM2 antagonists and HMT inhibitors are being developed as cancer therapeutics. Wild-type p53 expressing HCT116 colon cancer cells were resistant to apoptosis in response to the MDM2 antagonist Nutlin-3a. However, co-treatment with the HMT inhibitor DZNep sensitized the cells to Nutlin-3a-induced apoptosis. This sensitization resulted from reduced activity of the Bcl-2 gene promoter and a reduction in Bcl-2 mRNA and protein. Surprisingly, DZNep reduced Bcl-2 expression in other colon cancer cell lines (RKO, SW48, and LoVo) but failed to sensitize them to Nutlin-3a. We found these cell lines express elevated levels of Bcl-2 or other Bcl-2-family proteins, including Bcl-xL, Mcl-1, and Bcl-w. Knockdown of Mcl-1 and/or treatment with specific or pan Bcl-2-family inhibitors (BH3 mimetics) sensitized RKO, SW48, and LoVo cells to apoptosis by Nutlin-3a. The results demonstrate 1) DZNep represses the Bcl-2 gene promoter and affects apoptosis sensitivity by reducing Bcl-2 protein expression, and 2) elevated expression of pro-survival Bcl-2 family members protects colon cancer cells from Nutlin-3a-induced apoptosis. Targeting Bcl-2 proteins via DZNep or BH3 mimetics could increase the therapeutic potential of MDM2-antagonists like Nutlin-3a in colon cancer.

PMID: 29394130 [PubMed - as supplied by publisher]

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EGFR expression in circulating tumor cells from high-grade Metastatic Sarcomas.

EGFR expression in circulating tumor cells from high-grade Metastatic Sarcomas.

Cancer Biol Ther. 2018 Feb 02;:0

Authors: Braun AC, de Mello CAL, Corassa M, Abdallah EA, Urvanegia AC, Alves VS, Troncarelli B, Díaz M, Nicolau UR, Souza E Silva V, Calsavara V, Paterlini-Brechót P, Chinen LTD

PMID: 29394136 [PubMed - as supplied by publisher]

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MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1.

MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1.

Cancer Biol Ther. 2018 Feb 02;:1-10

Authors: Maolakuerban N, Azhati B, Tusong H, Abula A, Yasheng A, Xireyazidan A

PMID: 29394133 [PubMed - as supplied by publisher]

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DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a.

DZNep represses Bcl-2 expression and modulates apoptosis sensitivity in response to Nutlin-3a.

Cancer Biol Ther. 2018 Feb 02;:0

Authors: Zhou Y, Perez RE, Duan L, Maki CG

PMID: 29394130 [PubMed - as supplied by publisher]

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Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1

Abstract

In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.

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The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: a 2-year follow-up prospective cohort study

Abstract

Purpose

To investigate the incidence rate, severity and risk factors of related lymphedema in breast cancer survivors.

Methods

A 2-year follow-up prospective study of 387 women who had operation from four hospitals from January 1, to December 31, 2014 was conducted. Limb volume was measured by circumference and symptoms were measured using questionnaires pre-treatment and 1, 3, 6, 12, 18, 24 months after surgery separately. The incidence rates and the severity of lymphedema were evaluated, respectively. Risk factors for the development of breast cancer-related lymphedema (BCRL) were analyzed using log-rank test and Cox regression.

Results

The incidences of BCRL were 4.4, 10.1, 15.2, 28.6, 31.2 and 32.5% at 1, 3, 6, 12, 18, 24 months after surgery, respectively, measured by Norman questionnaire. The rates measured by arm circumference were 2.5, 6.7, 13.4, 21.4, 26.3 and 29.4%, respectively. About 114 (29.4% of 387) women were diagnosed with BCRL, and 78 of them got mild lymphedema. Axillary lymph node dissection (ALND) (HR = 5.2, 95% CI 1.6–17.3), radiotherapy (HR = 3.9, 95% CI 2.0–7.5), modified radical mastectomy (MRM) (HR = 2.1, 95% CI 1.3–3.4), the number of positive lymph nodes (HR = 1.1, 95% CI 1.0–1.2) and body mass index (BMI) (HR = 1.1, 95% CI 1.0–1.1) were independent risk factors for BCRL.

Conclusions

BCRL is a common complication for breast cancer patients after surgery. It can be fairly diagnosed only 1 month post-operation and the cumulative incidence of BCRL seems to be increasing over time, especially in the first year after surgery. ALND, radiotherapy, MRM, the number of positive axillary lymph nodes and BMI were found to be independent risk factors in the development of BCRL in this study.

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Skin involvement in Burkitt’s lymphoma

Publication date: Available online 2 February 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Dhwanee Thakkar, Lipika Lipi, Ruchira Misra, Satya Prakash Yadav

http://ift.tt/2DZkPsm

Beliefs about hydroxyurea in youth with sickle cell disease

Publication date: Available online 2 February 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sherif M. Badawy, Alexis A. Thompson, Robert I. Liem
BackgroundHydroxyurea reduces complications and improves health-related quality of life (HRQOL) in sickle cell disease (SCD) patients, however adherence remains suboptimal. Understanding patients' views of hydroxyurea is critical to optimize adherence, particularly in adolescents and young adults (AYA). Study objectives were to assess beliefs about hydroxyurea using the Beliefs about Medicines Questionnaire (BMQ), and to examine the relationship of patients' beliefs to their hydroxyurea adherence and HRQOL.MethodsThirty-four AYA with SCD participated in a cross-sectional study January–December 2015. Study assessments included BMQ to examine beliefs about hydroxyurea; Visual Analogue Scale (VAS) to assess hydroxyurea adherence; and Patient Reported Outcomes Measurement Information System (PROMIS®) to evaluate HRQOL.ResultsParticipants (41% female, 91% Black) had median age of 13.5 (IQR 12–18) years. Participants' concerns about overuse of medications correlated with concerns about hydroxyurea (rs = 0.36, p = 0.04) and overall harm of medications (rs = 0.5, p = 0.003). Participants' age positively correlated with the necessity of hydroxyurea (rs = 0.45, p = 0.007). Participants' concerns about hydroxyurea and overuse of medications positively correlated with anxiety (rs = 0.41, p = 0.02; rs = 0.44, p = 0.01) and depression (rs = 0.37, p = 0.04; rs = 0.54, p = 0.001), but inversely correlated with peer relationships (rs = −0.45, p = 0.03; rs = −0.44, p = 0.03), respectively, suggesting better HRQOL with concerns. Fifty percent of participants reported low hydroxyurea adherence (VAS < 80%), which was more seen in patients with higher concerns about hydroxyurea (p = 0.02).ConclusionsBeliefs about hydroxyurea correlated with HRQOL scores and adherence levels. Addressing patients' concern about hydroxyurea and medications overall as well as routine assessment of adherence and beliefs could help to overcome adherence barriers.

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Age adjusted hematopoietic stem cell transplant comorbidity index predicts survival in a T cell depleted cohort

Publication date: Available online 3 February 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig
ObjectivesAllogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria.MethodsA retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was performed. Kaplan-Meier's curve, log-rank tests, Cox model and Pearson correlation was used in the analysis.ResultsOf the 114 patients that underwent allogeneic transplant in our institution, 75.4% were ≥40 years old. More than 58% had a DLCO ≤80%. Although scores were positively correlated (correlation coefficient 0.43, p < 0.001), HCT-CI/Age more accurately predicted 2 year-overall survival (OS) and non-relapse mortality (NRM) in patients with lower (0–4) and higher (5–7) scores (52% and 36% versus 24% and 76%, p = 0.004, 0.003 respectively). PAM score did not reach statistical significance for difference in OS nor NRM between the low (<24) and high-risk (≥24) groups (p = 0.19 for both).ConclusionsDespite our small sample population, HCT-CI/Age was more discriminative to identify patients with poor outcome that might benefit from intensified management strategies or other therapeutic approaches rather than allogeneic HCT.

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