Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples

Abstract

Background

Next Generation Sequencing (NGS) has become a valuable tool for molecular landscape characterization of cancer genomes, leading to a better understanding of tumor onset and progression, and opening new avenues in translational oncology. Formalin-fixed paraffin-embedded (FFPE) tissue is the method of choice for storage of clinical samples, however low quality of FFPE genomic DNA (gDNA) can limit its use for downstream applications.

Methods

To investigate the FFPE specimen suitability for NGS analysis and to establish the performance of two solution-based exome capture technologies, we compared the whole-exome sequencing (WES) data of gDNA extracted from 5 fresh frozen (FF) and 5 matched FFPE lung adenocarcinoma tissues using: SeqCap EZ Human Exome v.3.0 (Roche NimbleGen) and SureSelect XT Human All Exon v.5 (Agilent Technologies).

Results

Sequencing metrics on Illumina HiSeq were optimal for both exome systems and comparable among FFPE and FF samples, with a slight increase of PCR duplicates in FFPE, mainly in Roche NimbleGen libraries. Comparison of single nucleotide variants (SNVs) between FFPE-FF pairs reached overlapping values >90 % in both systems. Both WES showed high concordance with target re-sequencing data by Ion PGM™ in 22 lung-cancer genes, regardless the source of samples. Exon coverage of 623 cancer-related genes revealed high coverage efficiency of both kits, proposing WES as a valid alternative to target re-sequencing.

Conclusions

High-quality and reliable data can be successfully obtained from WES of FFPE samples starting from a relatively low amount of input gDNA, suggesting the inclusion of NGS-based tests into clinical contest. In conclusion, our analysis suggests that the WES approach could be extended to a translational research context as well as to the clinic (e.g. to study rare malignancies), where the simultaneous analysis of the whole coding region of the genome may help in the detection of cancer-linked variants.

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Decreased expression of stomatin predicts poor prognosis in HER2-positive breast cancer

Abstract

Background

Human epidermal growth factor receptor-2 (HER2) is a transmembrane tyrosine kinase receptor that is overexpressed in 25 to 30 % of human breast cancers and is preferentially localized in lipid rafts. Stomatin is a membrane protein that is absent from the erythrocyte plasma membrane in patients with congenital stomatocytosis and is the major component of the lipid raft.

Results

In a total of 68 clinical cases of HER2-positive breast cancer, the absence of stomatin expression was associated with a decreased 5-year survival (65 % vs. 93 %, p = 0.005) by survival analysis. For stage I-III HER2-positive breast cancer, the absence of stomatin expression was associated with a decreased 5-year disease-free survival (57 % vs. 81 %, p = 0.016) and was an independent prognostic factor by multivariate analysis. Negative stomatin expression predicts distant metastases in a hazard ratio of 4.0 (95 % confidence interval from 1.3 to 12.5).

Conclusions

These results may suggest that stomatin is a new prognostic indicator for HER2-positive breast cancer.

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Advanced MRI manifestations of trigeminal ganglioneuroma: a case report and literature review

Abstract

Background

Ganglioneuroma is a rare benign tumor originating from the sympathetic nerves, and its origination from the trigeminal nerves is even rarer. Only 4 cases of ganglioneuroma originating from the trigeminal nerve have previously been reported, and these studies only reported conventional MRI manifestations. To our knowledge, the advanced MRI features of trigeminal ganglioneuroma have not been reported thus far.

Case presentation

This study reports a case of trigeminal ganglioneuroma in the left cerebellopontine angle. Advanced MRI showed the following tumor characteristics: significantly increased perfusion on perfusion imaging; isointense on diffusion-weighted imaging, whorled appearance within the tumor and no significant signs of damage to the white matter fiber tracts in the fractional anisotropy color map, and compare to the adjacent brain tissue, Choline didn't show markedly elevation, and N-acetylaspartate peak showed slightly reduction on magnetic resonance spectroscopy. The tumor was completely resected, and the diagnosis of ganglioneuroma was confirmed by postoperative pathological examination.

Conclusion

This case demonstrates the conventional as well as advanced MRI manifestations of this rare extra-axial tumor, which have never been previously reported. In addition, we reviewed the literature to demonstrate the advanced MRI features of trigeminal ganglioneuroma, in order to aid preoperative diagnosis and differentiation.

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Validation of the flemish CARES, a quality of life and needs assessment tool for cancer care

Abstract

Background

The Cancer Rehabilitation Evaluation System (CARES) is a quality of life (QOL) and needs assessment instrument of US origin that was developed in the 90's. Since November 2012 the copyright and user fee were abolished and the instrument became publicly available the present study aims to reinvestigate the psychometric properties of the CARES for the Flemish population in Belgium.

Methods

The CARES was translated into Flemish following a translation-back translation process. A sample of 192 cancer patients completed the CARES, concurrent measures, and questions on socio-demographic and medical data. Participants were asked to complete the CARES a second time 1 week later, followed by some questions on their experiences with the instrument. Internal consistency, test-retest reliability, content validity, construct validity, concurrent validity and feasibility of the CARES were subsequently assessed.

Results

The Flemish CARES version demonstrated excellent reliability with high internal consistency (range .87–.96) and test-retest ratings (range .70–.91) for all summary scales. Factor analysis replicated the original factor solution of five higher order factors with factor loadings of .325–.851. Correlations with other instruments ranging from |.43|–|.75| confirmed concurrent validity. Feasibility was indicated by the low number of missing items (mean 2.3; SD 5.0) and positive feedback of participants on the instrument.

Conclusions

The Flemish CARES has strong psychometric properties and can as such be a valid tool to assess cancer patients' QOL and needs in research, for example in international comparisons. The positive feedback of participants on the CARES support the usefulness of this tool for systematic assessment of cancer patients' well-being and care needs in clinical practice.

Trial registration

ClinicalTrials.gov: NCT02282696 (July 16, 2014).

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MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy

Abstract

Background

Pathologic complete response (pCR) after neoadjuvant chemotherapy for breast cancer is associated with improved prognosis in aggressive tumor subtypes, including ERBB2- positive tumors. Recent adoption of pCR as a surrogate endpoint for clinical trials in early stage breast cancer in the neoadjuvant setting highlights the need for biomarkers that, alone or in combination, help predict the likelihood of response to treatment.

Methods

Biopsy specimens from 29 patients with invasive ductal carcinoma treated with trastuzumab-based therapy prior to definitive resection and pathologic staging were evaluated by dual color bright field in situ hybridization (dual ISH) using probes for MET, TOP2A, PTEN, and PIK3CA genes, each paired with centromeric probes to their respective chromosomes (chromosomes 7, 17, 10, and 3). Ki-67 expression was assessed by immunohistochemistry (IHC). Various parameters describing copy number alterations were evaluated for each gene and centromere probe to identify the optimal parameters for clinical relevance. Combinations of ISH parameters and IHC expression for Ki-67 were also evaluated.

Results

Of the four genes and their respective chromosomes evaluated by ISH, two gene copy number parameters provided statistically significant associations with pCR: MET gain or loss relative to chromosome 7 (AUC = 0.791, sensitivity = 92 % and specificity = 67 % at optimal cutoff, p = 0.0032) and gain of PTEN (AUC = 0.674, sensitivity = 38 % and specificity = 100 % at optimal cutoff, p = 0.039). Ki-67 expression was also found to associate significantly with pCR (AUC = 0.726, sensitivity = 100 % and specificity = 42 % at optimal cutoff, p = 0.0098). Combining gain or loss of MET relative to chromosome 7 with Ki-67 expression further improved the association with pCR (AUC = 0.847, sensitivity = 92 % and specificity = 83 % at optimal cutoffs, p = 0.0006).

Conclusions

An immunogenotypic signature of low complexity comprising MET relative copy number and Ki-67 expression generated by dual ISH and IHC may help predict pCR in ERBB2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. These findings require validation in additional patient cohorts.

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Induction Chemotherapy Followed by Radiotherapy versus Concurrent Chemoradiotherapy in elderly patients with nasopharyngeal carcinoma: finding from a propensity-matched analysis

Abstract

Background

To date, no guideline is proposed for elderly nasopharyngeal carcinoma (NPC) due to lack of prospective clinical trials. The present study comparing the survivals and toxicities in elderly NPC patients received either induction chemotherapy followed by radiotherapy(IC + RT) or concurrent chemoradiotherapy (CCRT) was therefore undertaken to provide a more accurate basis for future clinical practice.

Methods

The eligible elderly NPC patients were retrospectively enrolled. Propensity score matching generated a matched cohort (1:2) composed from CCRT and IC + RT groups. The survivals and treatment-induced toxicities were compared between two groups. Multivariable analysis was carried to identify significant prognostic factors.

Results

The 5-year overall survival, cancer-specific survival, locoregional failure-free survival, distant failure-free survival for all patients were 58.3 %, 62.7 %, 88.7 %, 83.0 %, respectively. No significant survival differences were found between CCRT and IC + RT groups in the propensity-matched cohort. In comparison with the patients who received IC + RT, patients who underwent CCRT were associated with more severe acute toxicities including leucopenia (30 % vs. 6.8 %, P = 0.005), anemia (20 % vs. 4.1 %, P = 0.027), mucositis (63.3 % vs. 34.2 %, P = 0.007), weight loss (23.4 % vs. 4.1 %, P = 0.009). Basicranial bone involvement was an independent prognostic factor that predicted all-cause death (HR = 0.553, 95 % CI 0.329–0.929; P = 0.025) and cancer specific death (HR = 0.558, 95 % CI 0.321–0.969; P = 0.038) in elderly patients.

Conclusions

In the context of no guideline for elderly NPC, the present study suggested IC + RT should be a preferable modality compared with CCRT, with similar treatment outcomes but less acute toxicities.

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Racial differences in six major subtypes of melanoma: descriptive epidemiology

Abstract

Background

Melanoma accounts for the majority of skin cancer deaths. It has over thirty different subtypes. Different races have been observed to differ in multiple aspects of melanoma.

Methods

SEER (Surveillance, Epidemiology, and End Results) data on six major subtypes, namely melanoma in situ (MIS), superficial spreading melanoma (SSM), nodular melanoma (NM), lentigo maligna melanoma (LMM), acral lentiginous melanoma malignant (ALM), and malignant melanoma NOS (NOS), were analyzed. The racial groups studied included NHW (non-Hispanic white), HW (Hispanic white), Black, and Asian/PI (Pacific Islanders). Univariate and multivariate analysis was conducted to quantify racial differences in patients' characteristics, incidence, treatment, and survival.

Results

Significant racial differences are observed in patients' characteristics. For all subtypes except for ALM, NHWs have the highest incidence rates, followed by HWs, while Blacks have the lowest. For ALM, HWs have the highest rate, followed by NHWs. In stratified analysis, interaction between gender and race is observed. For the first five subtypes and localized and regional NOS, the dominating majority of patients had surgery, while for distant NOS, the distribution of treatment is more scattered. Significant racial differences are observed for distant ALM and NOS. For MIS, SSM, NM, LMM, and ALM, there is no significant racial difference in survival. For NOS, significant racial differences in survival are observed for the localized and regional stages, with NHWs having the best and Blacks having the worst five-year survival rates.

Conclusions

Racial differences exist for the six major melanoma subtypes in the U.S. More data collection and analysis are needed to fully describe and interpret the differences across racial groups and across subtypes.

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Potential Clinical Applications of 18 F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Mammography in Breast Cancer

Abstract

The whole-body positron emission tomography (PET)/magnetic resonance (MR) scan is a cutting edge technology providing comprehensive structural information from MR imaging and functional features from PET in a single session. Recent research findings and clinical experience have shown that ¹⁸F-fluorodeoxyglucose (FDG) whole-body PET/MR imaging has a diagnostic performance comparable with or superior to that of PET/CT in the field of oncology, including for breast cancer. In particular, FDG PET/MR mammography in the prone position with the breast hanging in a pendant manner can provide more comprehensive information about the metabolism, anatomy, and functional features of a breast lesion than a whole-body PET/MR scan. This article reports on current state-of-the-art PET/MR mammography in patients with breast cancer and the prospects for potential application in the future.

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Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial–mese...

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Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma

In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the ...

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Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma

Abstract

Background

In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the underlying molecular mechanisms remain unclear.

Methods

The effects of ATO on the migratory and invasive capacities of chondrosarcoma cells were investigated by Wound healing, Transwell and EMT assays. The expression of miR-125b in human chondrosarcoma tissues and cell lines was detected by real-time PCR analysis. Bisulfite sequencing analysis (BSP) was used to detect the effects of ATO on the expression of miR-125b. The gain-of-function and loss-of-function experiments were performed on chondrosarcoma cell lines to investigate the effects of miR-125b on chondrosarcoma invasion, and to determine whether signal transducer and activator of transcription 3(Stat3) mediates these effects. Dual-luciferase reporter assay was used to identify whether Stat3 is a direct target of miR-125b.

Results

MiR-125b was significantly downregulated in human metastatic chondrosarcoma tissues and cell lines but not in non-metastatic chondrosarcoma tissues. ATO up-regulates the expression of miR-125b by the demethylation of DNA. ATO induces MET and attenuates the invasive capacities of chondrosarcoma cells through miR-125b. Stat3 was verified as a direct target of miR-125b, which is involved in ATO regulating EMT-associated traits.

Conclusions

These findings, for the first time, provides evidence that the miR-125b-mediated inhibition of Stat3 is involved in the ATO-induced attenuation of metastasis in chondrosarcoma cells.

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Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Abstract

Background

Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial–mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β. ILK and RI gene both locate on chromosome 11p15 and the two genes are always at the adjacent position of same chromosome during evolution, which suggest that ILK and RI could have some relationship. However, underlying interacting mechanisms remain unclear between them. Here, we postulate that RI might regulate ILK signaling pathway via interacting with ILK.

Methods

Co-immunoprecipitation, GST pull-down and co-localization under laser confocal microscope assay were used to determine the interaction between ILK and RI exogenously and endogenously. Furthermore, we further verified that there is a direct binding between the two proteins by fluorescence resonance energy transfer (FRET) in cells. Next, The effects of interplay between ILK and RI on the key target protein expressions of PI3K/AKT/mTOR signaling pathway were determined by western blot, immunohistochemistry and immunofluorescence assay in vivo and in vitro. Finally, the interaction was assessed using nude mice xenograft model.

Results

We first found that ILK could combine with RI both in vivo and in vitro by GST pull-down, co-immunoprecipitation (Co-IP) and FRET. The protein levels of ILK and RI revealed a significant inverse correlation in vivo and in vitro. Subsequently, The results showed that up-regulating ILK could increase cell proliferation, change cell morphology and regulate cell cycle. We also demonstrated that the overexpression of ILK remarkably promoted EMT and expressions of target molecules of ILK signaling pathways in vitro and in vivo. Finally, we found that ILK overexpression significantly enhanced growth, metastasis and angiogenesis of xenograft tumor; Whereas, RI has a contrary role compared to ILK in vivo and in vitro.

Conclusions

Our findings, for the first time, directly proved that the interplay between ILK and RI regulated EMT via ILK/PI3K/AKT signaling pathways for bladder cancer, which highlights the possibilities that ILK/RI could be valuable markers together for the therapy and diagnosis of human carcinoma of urinary bladder.

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Impact of metronomic neoadjuvant chemotherapy on early tongue cancer

Abstract

Purpose

A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone.

Methods

In this retrospective study, 117 patients with stages I–II tongue cancer, who had undergone surgery, were divided into the "surgery group" or "metronomic neoadjuvant chemotherapy with bleomycin (15 mg × 6) group." The rate of overall survival was the primary outcome measure; the secondary outcome measures included the rates of distant metastasis, regional recurrence, and local recurrence.

Results

Of these patients, 54 underwent surgery alone and 63 received neoadjuvant chemotherapy. Neoadjuvant chemotherapy increased overall survival (76 vs. 90 %, P = 0.039). The neoadjuvant chemotherapy group had a significantly lower rates of distant metastasis (0 vs. 13 %, P = 0.003). There was no chemotherapy-related death.

Conclusions

Metronomic neoadjuvant chemotherapy decreased the rates of distant metastasis and increased the overall survival of tongue tumor patients.

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Radiotherapy for Non-Hodgkin’s lymphoma: still standard practice and not an outdated treatment option

Abstract

Two large, recently published observational studies demonstate a clear down-trend in the use of radiotherapy (RT) over the last 15 years, both in the setting of follicular and diffuse large B-cell lymphoma. This change of practice might have a negative impact on clinical outcome. Even within the context of modern systemic therapy, omission of RT translates not only into a shorter progression-free survival (PFS), but also into a worse overall survival (OS). RT should therefore remain standard practice.

This short review is aiming to summarize current guidelines and the best evidence available in the management of non-Hodgkin's lymphoma. Potentially practice changing, ongoing trials will be highlighted.

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Burden of preventable cancers in India: Time to strike the cancer epidemic

Publication date: Available online 30 August 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Ajeet Kumar Gandhi, Pavnesh Kumar, Menal Bhandari, Bharti Devnani, Goura Kishor Rath
India has a rapidly growing population inflicted with cancer diagnosis. From an estimated incidence of 1.45 million cases in 2016, the cancer incidence is expected to reach 1.75 million cases in 2020. With the limitation of facilities for cancer treatment, the only effective way to tackle the rising and humongous cancer burden is focusing on preventable cancer cases. Approximately, 70% of the Indian cancers (40% tobacco related, 20% infection related and 10% others) are caused by potentially modifiable and preventable risk factors. We review these factors with special emphasis on the Indian scenario. The results may help in designing preventive strategies for a wider application.



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Impact of metronomic neoadjuvant chemotherapy on early tongue cancer

Abstract

Purpose

A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone.

Methods

In this retrospective study, 117 patients with stages I–II tongue cancer, who had undergone surgery, were divided into the "surgery group" or "metronomic neoadjuvant chemotherapy with bleomycin (15 mg × 6) group." The rate of overall survival was the primary outcome measure; the secondary outcome measures included the rates of distant metastasis, regional recurrence, and local recurrence.

Results

Of these patients, 54 underwent surgery alone and 63 received neoadjuvant chemotherapy. Neoadjuvant chemotherapy increased overall survival (76 vs. 90 %, P = 0.039). The neoadjuvant chemotherapy group had a significantly lower rates of distant metastasis (0 vs. 13 %, P = 0.003). There was no chemotherapy-related death.

Conclusions

Metronomic neoadjuvant chemotherapy decreased the rates of distant metastasis and increased the overall survival of tongue tumor patients.

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Radioimmunotherapy with 131 I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma

Abstract

Purpose

The aim of this study was to assess the clinical activity and toxicity of ¹³¹I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone).

Methods

Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled.

Results

A total of 16 patients were enrolled and treated with a single dose of ¹³¹I-rituximab as consolidation therapy after the completion of six or eight cycles of R-CHOP between December 2005 and June 2011. This trial was terminated before the scheduled enrollment owing to low recruitment. Among the 16 patients who were treated with consolidative ¹³¹I-rituximab, 6 achieved complete response (CR) after three cycles of R-CHOP, and another 9 patients further achieved CR after the completion of six or eight cycles of R-CHOP. During the median follow-up period of 73 months, only four patients (25 %) experienced relapse. Two-year relapse-free survival was 88 %, and 5-year relapse-free survival was 81 %. Grade 3 or 4 treatment-related toxicity occurred in four patients and included neutropenia and thrombocytopenia.

Conclusions

¹³¹I-rituximab showed promising efficacy as consolidation treatment for patients with DLBCL. A future randomized phase III study to confirm our results is warranted.

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Tart cherry supplementation improves working memory, hippocampal inflammation, and autophagy in aged rats

Abstract

High consumption of fruits and vegetables has been associated with reduced risk of debilitating diseases and improved cognition in aged populations. These beneficial effects have been attributed to the phytochemicals found in fruits and vegetables, which have previously been shown to be anti-inflammatory and modulate autophagy. Tart cherries contain a variety of potentially beneficial phytochemicals; however, little research has been done to investigate the effects of tart cherry on the aging brain. Therefore, the purpose of this study was to determine if tart cherry supplementation can improve cognitive and motor function of aged rats via modulation of inflammation and autophagy in the brain. Thirty 19-month-old male Fischer 344 rats were weight-matched and assigned to receive either a control diet or a diet supplemented with 2 % Montmorency tart cherry. After 6 weeks on the diet, rats were given a battery of behavioral tests to assess for strength, stamina, balance, and coordination, as well as learning and working memory. Although no significant effects were observed on tests of motor performance, tart cherry improved working memory of aged rats. Following behavioral testing, the hippocampus was collected for western/densitometric analysis of inflammatory (GFAP, NOX-2, and COX-2) and autophagy (phosphorylated mTOR, Beclin 1, and p62/SQSTM) markers. Tart cherry supplementation significantly reduced inflammatory markers and improved autophagy function. Daily consumption of tart cherry reduced age-associated inflammation and promoted protein/cellular homeostasis in the hippocampus, along with improvements in working memory. Therefore, addition of tart cherry to the diet may promote healthy aging and/or delay the onset of neurodegenerative diseases.

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The methodological ‘revolution’: caution accepted

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Clinico-pathological Study of Limb Salvage Surgery for Osteosarcoma: Experience in a Rural Cancer Center

Abstract

Although recent multimodality therapeutic protocols have led to improved survival in osteosarcoma (OS), the outcome still remains dismal. Ongoing international multicentric trials on OS aim to randomize patients for optimum management, based on histological response to NACT. The pathologic response to neoadjuvant chemotherapy (NACT) is the most important factor predicting prognosis. In this study of 23 cases of limb salvage surgery post neoadjuvant chemotherapy, mean age was 18.3 years, with male predominance. 65.5 % cases were conventional OS. Histologic assessment of chemotherapeutic effect done by Huvos grading revealed good response (Huvos lll and lV) in 15 (65.2 %) and poor response (Huvos l and ll) in eight (34.8 %). A scoring based on MRI with a scale of 1–6 was compared with histologic response. Five (62.5 %) of poor responders showed score of >3 and 73.3 % of good responders showed ≤3. Dose intensity of NACT was calculated and correlated with the histological response. 53.3 % of good responders showed ARDI > 0.9. Five (21.7 %) developed local recurrence and 10(43.4 %) had pulmonary metastasis. Adoption of more aggressive treatment modalities may ensure better histologic response and longer event free survival.

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Ficolin-2 binds to HIV-1 gp120 and blocks viral infection

Abstract

Ficolin-2 is a lectin complement pathway activator present in normal human plasma and usually associated with infectious diseases, but little is known about the role of ficolin-2 in human immunodeficiency virus (HIV) infection. Here, we describe our novel findings that serum ficolin-2 concentrations of 103 HIV-1 patients were much higher compared to those of 57 healthy donors. In vitro analysis showed that HIV-1 infection could enhance ficolin-2 expression. We further demonstrated that recombinant ficolin-2 protein could bind with HIV-1 envelope glycoprotein gp120, and subsequently induce complement dependent cytotoxicity. Moreover, ficolin-2 could block the entry of HIV-1 into target cells (TZM-b1 and MT-2 cells) and infection in a ficolin-2 dosedependent manner. To our knowledge, this is the first report about the protective role of ficolin-2 against HIV-1 infection and our study suggests that ficolin-2 is an important human innate immune molecule against HIV.

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Preoperative endoscopic localization of colorectal cancer and tracing lymph nodes by using carbon nanoparticles in laparoscopy

Abstract

Background

The objective of this study is to evaluate the effectiveness of preoperative endoscopic localization of colorectal cancer and tracing lymph nodes by carbon nanoparticle tattooing in laparoscopic colorectal cancer surgery.

Methods

From January 2013 to December 2014, 54 patients with colorectal cancer were recruited and divided into experimental (n = 27) and control (n = 27) groups. The patients in the experimental group were localized preoperatively by endoscopic carbon nanoparticle tattooing, whereas patients in the control group were not tattooed.

Results

All injection sites in the experimental group were visible to surgeons. No abdominal pain, fever, diarrhea, and other symptoms of infection were found in the experimental group. The time for detecting the tumor (2.71 ± 2.13 min versus 6.91 ± 5.16 min, p < 0.001), operation time (151.22 ± 30.66 min versus 170.26 ± 33.13 min, p = 0.033), and blood loss during the operation (125.04 ± 29.48 mL versus 147.52 ± 34.35 mL, p = 0.013) were lower in the experimental group than in the control group. Average numbers of dissected lymph nodes in the experimental group exceeded those in the control group (14.41 ± 3.32 versus 8.96 ± 2.90, p < 0.001), and the rate of dissected lymph nodes ≥12 was higher in the experimental group than in the control group (70.37 versus 37.04 %, p < 0.001). Moreover, no difference in postoperative complications was found between the two groups.

Conclusions

Tattooing colorectal cancer with carbon nanoparticles in laparoscopic colorectal cancer surgery is safe and useful both in localization and lymph node tracing.

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Emergency management with resection versus proximal stoma or stent treatment and planned resection in malignant left-sided colon obstruction

Abstract

Background

Emergency surgery for colon cancer, as a result of obstruction, has been vitiated by a high frequency of complications and poor survival. The concept of "bridge to surgery" includes either placement of self-expanding metallic stents (SEMS) or diverting stoma of an obstructing tumour and subsequent planned resection. The aim of this study was to compare acute resection with stoma or stent and later resection regarding surgical and oncological outcomes and total hospital stay.

Methods

This is a retrospective cohort study. All 2424 patients diagnosed with colorectal cancer during 1997–2013 were reviewed. All whom underwent acute surgery with curative intention for left-sided malignant obstruction were included in the study.

Results

One hundred patients fulfilled the inclusion criteria. Among them, 57 patients were treated with acute resection and 43 with planned resection after either acute diverting colostomy (n = 23) or stent placement (n = 20). The number of harvested lymph nodes in the resected specimen was higher in the planned resection group compared with acute resection group (21 vs. 8.7; p = 0.001). Fewer patients were treated with adjuvant chemotherapy in the acute resection group than in the stoma group (14 % (8/57 patients) vs. 43 %, (10/23 patients; p = 0.024)). Patients operated with acute resection had a higher 30-day mortality rate and were more frequently left with a permanent stoma.

Conclusions

Decompression of emergency obstructive left colon cancer with stent or stoma and subsequent curative resection appears safer and results in a higher yield of lymph node harvest, and fewer patients are left with a permanent stoma.

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Developments in neuro-oncology

Summary

A short statement on the most recent developments in the neuro-oncology field, including the new WHO Classification of Tumors of the Central Nervous System (2016) and current treatment strategies.

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Patterns of Failure in Pediatric Rhabdomyosarcoma Following Proton Therapy

Publication date: Available online 30 August 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Tamara Z. Vern-Gross, Daniel J. Indelicato, Julie A. Bradley, Ronny L. Rotondo
PurposeWe report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy.Patients and MethodsBetween February 2007 and November 2013, 66 children with a median age of 4.1years (range, 0.6-15.3 years) diagnosed with non-metastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 (CTV1) was defined as the prechemotherapy tumor plus a 1-cm anatomically-constrained margin. CTV2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5 cm anatomically-constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis.ResultsOf the 66 children, 11 developed locally progressive disease at a median of 16 months (range, 14-32 months) for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7 years (range 0.6-16 years) and 6 cm (range, 2-8 cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3 and all 11 were group III. Of the relapses, 100% (11/11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field.ConclusionEarly data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm CTV1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features.

Teaser

This study examines patterns of failure in children who received proton therapy for rhabdomyosarcoma. Routine use of a small CTV margin in the setting of highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features. The patterns of failure suggest improvements in local control will come through dose escalation of select high-risk tumors rather than larger CTV margins.


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From Röntgen-rays to carbon ion therapy: The evolution of modern radiation oncology in Germany

Publication date: Available online 30 August 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jonathan W. Lischalk, Laila König, Michael C. Repka, Matthias Uhl, Anatoly Dritschilo, Klaus Herfarth, Jürgen Debus
Beginning with the discovery of X-rays in 1895, German scientists and clinicians were instrumental in establishing the fields of diagnostic and therapeutic radiology, creating the first radiotherapy peer-reviewed journal, and holding the first international oncologic conference. These landmark achievements profoundly influenced the nascent field of radiation oncology. However, the rapid early scientific progress was first halted by World War I, derailed during World War II, and was slowly reestablished amid the divisions of the Cold War. Figure 1 chronicles many radiotherapy milestones during these distinct periods. Today, Germany has reemerged as a scientific leader in the field of radiotherapy, and a pioneer in basic radiobiology research and clinical implementation of particle therapy. Here we explore the technical advances as well as the clinical evolution of radiotherapy in Germany from the groundbreaking establishment of Bismarck's healthcare system to a modern view of radiotherapy practice.

Teaser

Germany, home of Wilhelm Conrad Röntgen discoverer of the X-ray, has played a critical role in the development of radiation oncology. Rapid initial scientific advances were stalled by sociopolitical turbulence during two World Wars and the Cold War only to reemerge in the modern era. We explore the technical advances and clinical evolution of radiotherapy in Germany from the groundbreaking establishment of Bismarck's healthcare system to a modern view of radiotherapy practice.


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Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma

Abstract

Survivin is an anti-apoptotic protein that is highly expressed in many cancers, including malignant gliomas. Preclinical studies established that the conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human glioma cells ex vivo. The current clinical study was conducted to test safety, immunogenicity and clinical effects of the vaccine. Recurrent malignant glioma patients whose tumors were survivin-positive, and who had either HLA-A*02 or HLA-A*03 MHC class I allele-positivity, were given subcutaneous injections of SurVaxM (500 μg) in Montanide ISA 51 with sargramostim (100 μg) at 2-week intervals. SurVaxM was well tolerated with mostly grade one adverse events (AE) and no serious adverse events (SAE) attributable to the study drug. Six patients experienced local injection site reactions; three patients reported fatigue (grades 1 and 2), and 2 patients experienced myalgia (grade 1). Six of eight immunologically evaluable patients developed both cellular and humoral immune responses to vaccine. The vaccine also stimulated HLA-A*02, HLA-A*03 and HLA-A*24 restricted T cell responses. Three patients maintained a partial clinical response or stable disease for more than 6 months. Median progression-free survival was 17.6 weeks, and median overall survival was 86.6 weeks from study entry with seven of nine patients surviving more than 12 months.

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Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma

Abstract

Survivin is an anti-apoptotic protein that is highly expressed in many cancers, including malignant gliomas. Preclinical studies established that the conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human glioma cells ex vivo. The current clinical study was conducted to test safety, immunogenicity and clinical effects of the vaccine. Recurrent malignant glioma patients whose tumors were survivin-positive, and who had either HLA-A*02 or HLA-A*03 MHC class I allele-positivity, were given subcutaneous injections of SurVaxM (500 μg) in Montanide ISA 51 with sargramostim (100 μg) at 2-week intervals. SurVaxM was well tolerated with mostly grade one adverse events (AE) and no serious adverse events (SAE) attributable to the study drug. Six patients experienced local injection site reactions; three patients reported fatigue (grades 1 and 2), and 2 patients experienced myalgia (grade 1). Six of eight immunologically evaluable patients developed both cellular and humoral immune responses to vaccine. The vaccine also stimulated HLA-A*02, HLA-A*03 and HLA-A*24 restricted T cell responses. Three patients maintained a partial clinical response or stable disease for more than 6 months. Median progression-free survival was 17.6 weeks, and median overall survival was 86.6 weeks from study entry with seven of nine patients surviving more than 12 months.

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Radiotherapy for Non-Hodgkin’s lymphoma: still standard practice and not an outdated treatment option

Two large, recently published observational studies demonstate a clear down-trend in the use of radiotherapy (RT) over the last 15 years, both in the setting of follicular and diffuse large B-cell lymphoma. Th...

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Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma

Abstract

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in 'low' and 'intermediate' Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81–0.99) and 0.76 (0.65–0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib's inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential.

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Patients treated with neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy in locally advanced cervical cancer: long-term outcomes, survival and prognostic factors in a single-center 10-year follow-up

Abstract

We report the long-term follow-up in patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy (NACT) + radical surgery (RS) + adjuvant chemotherapy (ACT) analyzing prognostic factors which may more influence, in a long time, the survival outcome using univariate and multivariate analysis. In this study, we included all patients with diagnosis of locally advanced cervical cancer (IB2-IIB) treated with NACT + RS + ACT from June 2000 and February 2007 as previously described by Angioli et al. (Gynecol Oncol 127(2):290–6, 2012). The primary end-point of the study was overall survival (OS) in patients with node metastases and in those without positive lymph nodes at the end of 10-year follow-up in order to confirm the prognostic role of nodes involvement for a long period. Moreover, we analyzed the impact of other prognostic factors, such as histotype, tumor size, grading and parametrial invasion. Secondary end-point was evaluated in the subgroup of patients with positive nodes the following prognostic factors: number of positive lymph nodes and site of positive lymph nodes. In the subgroup of patients with positive nodes, the OS was 63 %, and in that with negative nodes, the OS was 75 %. On multivariate analysis, the number of nodal metastases, parametrial involvement, grading and the lesion diameter were noted to be significant factors in determining OS. Neither the histotype nor the lymph nodal site is related to survival. Results suggest that CT alone may be an alternative postoperative therapy for patients with cervical cancer.

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Hypofractionation with no boost after breast conservation in early-stage breast cancer patients

Abstract

The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6–124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good–excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity.

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Cancer Stem Cells in Human Gastrointestinal Cancer

Summary

Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, exhibit high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs present. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

This article is protected by copyright. All rights reserved.

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Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non–small cell lung cancer

Summary

Next-generation sequencing (NGS) and digital polymerase chain reaction (PCR) technologies allow analysis of the mutational profile of circulating cell-free DNA (cfDNA) in individuals with advanced lung cancer. We have now evaluated the feasibility of cfDNA sequencing for mutation detection in patients with non–small cell lung cancer (NSCLC) at earlier stages. A total of 150 matched tumor and serum samples were collected from NSCLC patients at stages IA–IIIA. Amplicon sequencing with DNA extracted from tumor tissue detected frequent mutations in EGFR (37% of patients), TP53 (39%), and KRAS (10%), consistent with previous findings. In contrast, NGS of cfDNA identified only EGFR, TP53, and PIK3CA mutations in three, five, and one patients, respectively, even though adequate amounts of cfDNA were extracted (median of 4,936 copies per milliliter of serum). NGS showed a high accuracy (98.8%) compared with droplet digital PCR for cfDNA mutation detection, suggesting that the low frequency of mutations in cfDNA was not due to a low assay sensitivity. Whereas the yield of cfDNA did not differ among tumor stages, the cfDNA mutations were detected in seven patients at stages IIA–IIIA and at T2b or T3. Tumor volume was significantly higher in the cfDNA mutation–positive patients than in the negative patients at stages T2b–T4 (159.1 ± 58.0 versus 52.5 ± 9.9 cm³, p = 0.014). Our results thus suggest that tumor volume is a determinant of the feasibility of mutation detection with cfDNA as the analyte.

This article is protected by copyright. All rights reserved.

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Intensity-specific effect of physical activity on urinary levels of 8-hydroxydeoxyguanosine in middle-aged Japanese

Summary

Physical activity (PA) is recommended to both promote and maintain health and prevent cancer by improving the body's DNA repair system, which is considered a mechanism of cancer prevention. However, associations between PA and urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), which reflects DNA damage, are unclear. This cross-sectional study included 2,370 men and 4,052 women aged 45-74 years enrolled between 2010 and 2012. Habitual PA was assessed via single-axis accelerometer and urinary 8-OH-dG levels via automated high-pressure liquid chromatography. Multiple linear regression analysis was used to examine the relationship between log-transformed urinary 8-OH-dG and total PA (TPA) and PA of moderate/vigorous intensity (MVPA; ≥3 metabolic equivalents [MET]), with adjustment for age, body mass index, energy intake, alcohol consumption, smoking status, daily coffee drinking, menopause status (in women), and TPA (for MVPA). On multivariate adjustment, urinary 8-OH-dG levels were inversely correlated with TPA (β = −0.020, P < 0.01) in women, and this correlation was not changed by PA intensity. Conversely, urinary 8-OH-dG levels were inversely correlated with MVPA (β = −0.022, P < 0.05) in men, although the correlation with TPA was non-significant. This inverse correlation was clearer in current smokers than in never or former smokers, although the interaction between smoking status and MVPA on urinary 8-OH-dG levels was non-significant. In conclusion, greater TPA in women and greater MVPA in men were correlated with reduction in urinary 8-OH-dG, suggesting sex-specific effects of MVPA and TPA on protection from oxidative DNA damage. Increasing PA may mediate reduction in oxidative stress.

This article is protected by copyright. All rights reserved.

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Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma

Abstract

Survivin is an anti-apoptotic protein that is highly expressed in many cancers, including malignant gliomas. Preclinical studies established that the conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human glioma cells ex vivo. The current clinical study was conducted to test safety, immunogenicity and clinical effects of the vaccine. Recurrent malignant glioma patients whose tumors were survivin-positive, and who had either HLA-A*02 or HLA-A*03 MHC class I allele-positivity, were given subcutaneous injections of SurVaxM (500 μg) in Montanide ISA 51 with sargramostim (100 μg) at 2-week intervals. SurVaxM was well tolerated with mostly grade one adverse events (AE) and no serious adverse events (SAE) attributable to the study drug. Six patients experienced local injection site reactions; three patients reported fatigue (grades 1 and 2), and 2 patients experienced myalgia (grade 1). Six of eight immunologically evaluable patients developed both cellular and humoral immune responses to vaccine. The vaccine also stimulated HLA-A*02, HLA-A*03 and HLA-A*24 restricted T cell responses. Three patients maintained a partial clinical response or stable disease for more than 6 months. Median progression-free survival was 17.6 weeks, and median overall survival was 86.6 weeks from study entry with seven of nine patients surviving more than 12 months.

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Retrospective analysis of HPV 16/18-related disease burden using archival clinical samples

Abstract

Purpose

Estimation of HPV-related disease burden lies at the core of effective disease management. HPV testing is heavily reliant on its retrospective detection in archival clinical cancer samples, especially in parts of the world where HPV screening is not routinely practiced. During the last decade, valuable insights were gained through regional reports based on occasional screening of cervical smears or biopsy sections for the presence of high-risk HPV. HPV 16 and 18 were found to be predominant high-risk HPV subtypes with some regional differences and incidences of co-infections, detected mostly through PCR-based methods. In cases of multiple infections, the presence of viral DNA may not signify its etiologic involvement. The current study, therefore, combines PCR-based detection method with the immunohistochemical (IHC) detection of early viral protein E6 expression, in order to obtain a reliable read out for the disease causing viral subtype, especially in cases of co-infections with oncogenic subtypes other than HPV 16 and 18. Immunohistochemistry (IHC) and PCR-based methods are routinely used laboratory techniques in local hospitals. The concordance between IHC and PCR-based analyses may be useful for determining effective method for the retrospective testing of HPV 16 and 18 disease-related burden.

Methods

A total of 49 paraffin-embedded cervical cancer biopsy sections representing patients from the northwest region of the country were collected from the tertiary care hospital for this study. Genotyping for HPV 16 and 18 was carried out through PCR. The HPV 16/18 E6 protein expression was evaluated by IHC and was compared with the clinicopathological features of cervical cancer.

Results

Molecular analysis of 33 (67 %), E6-expressing paraffin-embedded cervical cancer biopsy sections revealed the presence of HPV 16 (n = 23; 47 %), HPV 18 (n = 6; 12 %) and co-infection (n = 4; 8 %) in 49 tumors through PCR. Despite the PCR-based detection of viral DNA in 37 cervical cancer samples, IHC analysis of E6 expression revealed the etiological involvement of HPV 16/18 in 33 out of 37 cervical cancer samples. Overall, there was 85 % concordance in the results of the two techniques.

Conclusion

IHC analysis provides more conclusive evidence regarding the etiological involvement of the viral subtypes, especially in the presence of multiple infections. About two-thirds (67 %) of cervical cancer samples were found to be caused due to HPV 16/18. Latent occurrence of HPV 16 and 18 is suggested in less than 10 % cervical cancer samples which were found to harbor viral DNA without E6 expression. Furthermore, E6 expression was found to be significantly correlated with the tumor grade.

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Aspirational characteristics for effective leadership of improvement teams

Abstract

Working on quality improvement has become an innate part of managing a pediatric radiology service. To help radiologists effectively lead improvement teams, eight aspirational characteristics are discussed. These are: 1) Be a good listener, 2) Effectively communicate around an accountability cycle, 3) Stress simplicity: Prioritization and pace, 4) Expend energy to optimize people development, 5) Lead with optimism, 6) Create a culture of wellness and sustainability, 7) Have a progressive attitude toward failure and 8) Project humility over arrogance.

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Radioimmunotherapy with 131 I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma

Abstract

Purpose

The aim of this study was to assess the clinical activity and toxicity of ¹³¹I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone).

Methods

Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled.

Results

A total of 16 patients were enrolled and treated with a single dose of ¹³¹I-rituximab as consolidation therapy after the completion of six or eight cycles of R-CHOP between December 2005 and June 2011. This trial was terminated before the scheduled enrollment owing to low recruitment. Among the 16 patients who were treated with consolidative ¹³¹I-rituximab, 6 achieved complete response (CR) after three cycles of R-CHOP, and another 9 patients further achieved CR after the completion of six or eight cycles of R-CHOP. During the median follow-up period of 73 months, only four patients (25 %) experienced relapse. Two-year relapse-free survival was 88 %, and 5-year relapse-free survival was 81 %. Grade 3 or 4 treatment-related toxicity occurred in four patients and included neutropenia and thrombocytopenia.

Conclusions

¹³¹I-rituximab showed promising efficacy as consolidation treatment for patients with DLBCL. A future randomized phase III study to confirm our results is warranted.

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Issue Contents

Publication date: September 2016
Source:Cancer/Radiothérapie, Volume 20, Supplement





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Avertissement aux lecteurs

Publication date: September 2016
Source:Cancer/Radiothérapie, Volume 20, Supplement





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Editorial Board

Publication date: September 2016
Source:Cancer/Radiothérapie, Volume 20, Supplement





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Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease

Abstract

Background

Vaso-occlusive episodes (VOEs) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in children and adults with SCD, with a secondary aim to assess pain relief and opioid consumption.

Procedure

Participants included children (<18 years) and adults with a VOE requiring hospitalization. Patients were randomly assigned to receive standard care (opioid patient-controlled analgesia; control group) or one dose of intravenous methadone (0.1–0.125 mg/kg) in addition to standard care (methadone group). Venous methadone and metabolite concentrations were measured. Pain scores, pain relief scores, and opioid consumption were recorded.

Results

Twenty-four children (12 methadone, 12 controls) and 23 adults (11 methadone, 12 controls) were studied. In children, the half-life of R- and S-methadone enantiomers was 34 ± 16 and 24 ± 9 hr, respectively. In adults, R- and S-methadone half-lives were 52 ± 17 and 38 ± 12 hr, respectively. Pain scores were lower (P = 0.002) and pain relief scores were higher (P = 0.0396) in children receiving methadone versus controls. There was no difference in pain scores and pain relief in adults receiving methadone versus controls. There was no difference in opioid consumption between methadone and control groups, in both adults and children.

Conclusions

Intravenous methadone disposition in children and adults with SCD was comparable to that in subjects without SCD from prior studies. Methadone produced more pain relief than standard care in children with SCD. Higher methadone doses may be more effective and should be evaluated in both children and adults with SCD.

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Development and evaluation of iManage: A self-management app co-designed by adolescents with sickle cell disease

Abstract

Background

Adolescents and young adults (AYAs) with sickle cell disease (SCD) are a vulnerable population with high risk of morbidity that could be decreased with effective self-management. Previous research suggests that mobile applications (apps) may facilitate AYA engagement in health-promoting behaviors. The objectives of this study were: (i) describe Internet access and use in AYA with SCD; (ii) identify barriers for self-management in this population; (iii) collaborate with AYA to co-design a mobile app that would minimize barriers; and (iv) evaluate the feasibility and acceptability of the app.

Procedure

In phase 1, 46 AYAs with SCD 16–24 years of age completed a survey of Internet access and use. During phase 2, 19 AYAs with SCD (average age 20 ± 2.5 years) and eight healthcare providers participated in interviews to identify barriers and co-design sessions to develop the app. In phase 3, five AYAs with SCD completed app feasibility and usability testing.

Results

AYAs with SCD had daily Internet access (69%) using their computers (84%) or mobile phones (70%). Participants went online for health information (71%) and preferred Web sites with interactive/social features (83%). Barriers to self-management included failing to believe that their health would suffer, lack of tailored self-management support, lack of a mechanism to visualize self-management progress, and limited opportunities for peer interaction around self-management. The prototype app (iManage) was rated as highly feasible and beneficial.

Conclusions

A mobile app prototype co-designed by AYAs with SCD may be a useful tool for engaging them in self-management strategies designed to improve health.

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Survival and complication rates in patients with thalassemia major in Taiwan

Abstract

Background

While transfusion and iron chelation therapy for thalassemia major (TM) has improved dramatically in recent years, the consequences of this improvement (current rates of survival and TM-related complications) remain unknown.

Methods

This nationwide population-based cohort study analyzed 2007–2011 data obtained from the Taiwanese National Health Insurance Research Database.

Results

After excluding those patients receiving hematopoietic stem cell transplantation, we enrolled 454 patients with TM who received transfusion and chelation therapy (median age, 17.2 years). Among these patients, the mortality rate was 2.9% in 2007, 2.3% in 2008, 2.9% in 2009, 2.6% in 2010, and 0.7% in 2011. Heart was the most common target organ of TM-related complications. There were 80 patients (17.6%) with arrhythmia and 86 patients (18.9%) with congestive heart failure. Dysfunction of endocrine organs was common, and the most common endocrinopathy was hypogonadism (23.1%), followed by diabetes (21.2%). There were 75 patients (16.5%) with liver cirrhosis and 79 patients (17.4%) with osteoporosis.

Conclusions

Adequate red blood cell transfusion and iron chelation is available to all patients with TM in Taiwan under the universal health insurance system, and has resulted in reduction of TM-related mortality to very low levels. As these patients get older, early detection of complications and adequate intervention are important to quality-of-life improvement.

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Homozygous α-thalassemia: Challenges surrounding early identification, treatment, and cure

Abstract

The prognosis for homozygous α-thalassemia is changing. Prenatal diagnosis and intrauterine transfusions (IUT) reduce maternofetal morbidity and mortality; hematopoietic stem cell transplant (HSCT) is curative. Empiric evidence to support IUT and HSCT to treat homozygous α-thalassemia is lacking. The first case of curative HSCT for homozygous α-thalassemia was reported in 1997. Nearly 20 years later, five additional reports are published. We review the literature and report an institutional experience with three homozygous α-thalassemia patients. The first died shortly after birth. The second underwent HSCT after years of chronic transfusion therapy. The third benefited from IUT and HSCT. These cases exemplify the varied outcomes associated with this condition.

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Predictive factors for resolution of childhood immune thrombocytopenia: Experience from a single tertiary center in Thailand

Abstract

Background

Initial clinical factors that can reliably predict a successful within-1-year resolution of childhood immune thrombocytopenia (ITP) are still unclear. This study aimed to determine factors associated with within-12-month resolution of newly diagnosed childhood ITP.

Methods

The hospital records of 417 consecutive children aged less than 15 years with ITP were reviewed retrospectively and data related to the initial presentation were noted. Logistic regression analysis was used to determine which presenting features were associated with a favorable outcome within 12 months.

Results

Significant clinical and laboratory predictors for resolution of newly diagnosed childhood ITP within 12 months were abrupt onset less than 14 days, age less than 5 years, and platelet count at 4 weeks postdiagnosis of at least 100 × 10⁹ l^–1. With these three significant predictors, the rate of within-1-year recovery was more than 97.2%, with a positive predictive value of 97.8% for newly diagnosed childhood ITP.

Conclusion

Age less than 5 years, onset of bleeding less than 14 days, and follow-up platelet count at 4 weeks of at least 100 × 10⁹ l^–1 are significant predictive factors for disease resolution among children with newly diagnosed ITP.

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Decreased fetal hemoglobin over time among youth with sickle cell disease on hydroxyurea is associated with higher urgent hospital use

Abstract

Background

Hydroxyurea (HU) induces dose-dependent increased fetal hemoglobin (HbF) for sickle cell disease (SCD). Large deviation from historical personal best (PBest) HbF, a clinic-based version of maximum dose, may identify a subset with suboptimal HU adherence over time.

Procedure

Retrospective clinical data from youth ages 10–18 years prescribed HU at two centers were extracted from medical records at three time points: pre-HU initiation, PBest and a recent assessment. Decrease from PBest HbF of 20% or more at recent assessment despite stable dosing was designated as high deviation from PBest. Acute hospital use was compared between 1-year periods, pre-HU and ±6 months for PBest and recent assessment. Groups were compared using descriptive and bivariate nonparametric statistics.

Results

Seventy-five youth, mean HU duration 5.9 years, met eligibility criteria. Mean ages of HU initiation, PBest and recent assessment were 8.0, 10.9 and 13.9 years, respectively. Despite stable dosing, average HbF of 19.5% at PBest overall declined by 31.8% at recent assessment. PBest HbF declined by 11.7 and 40.1% in two groups, the latter comprised 70.7% of the sample, had lower pre-HU and recent HbF and higher dosing. They experienced more urgent hospital use during the year framing recent assessment than during PBest; these findings were supported by sensitivity analysis.

Conclusions

Decline from PBest HbF is a novel approach to assess HU effectiveness, is common among youth and may represent suboptimal adherence. Larger prospective studies using additional adherence measures are needed to confirm our approach of tracking HbF deviation over time and to define an appropriate cutoff.

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Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population

Abstract

Background

Neuropathic pain (NP) after definitive surgery for extremity osteosarcoma (OS) has not been previously characterized. This study prospectively investigates the incidence, duration, and treatment of NP in limb sparing surgery and amputation groups.

Procedure

In patients treated for OS on a chemotherapy and definitive surgery (limb sparing vs. amputation) protocol (OS08), we prospectively collected the following data: (i) demographical data (age, sex, race); (ii) NP time of onset and duration; and (iii) dose (starting, maximum) and duration of gabapentin, amitriptyline, and methadone treatment.

Results

Thirty-seven patients underwent 38 definitive surgeries: limb sparing (26, 68.4%) or amputations (12, 31.6%). Localization included lower extremity (30, 81%), upper extremity (6, 16%), or pelvis (1, 3%). Thirty patients (81%) developed NP and 26 of them required NP-specific medications (87.7%). The mean [standard deviation (SD)] duration of NP was 6.5 weeks (7.2) (median 4.4, range 0.3–29.9). All 26 patients (27 surgeries) treated with NP medications received gabapentin, either as single therapy (65.4%) (17 patients, 18 surgeries), dual therapy with gabapentin and amitriptyline (five patients), or triple therapy with gabapentin, amitriptyline, and methadone (four patients). The mean starting (maximum) doses of gabapentin, amitriptyline, and methadone (mg/kg/day) were 20.2 (43.8), 0.5 (0.7), and 0.3 (0.3), respectively. The incidence and duration of NP, duration of treatment, and NP-specific dose regimens were similar in the limb sparing and the amputation groups.

Conclusions

NP after definitive surgery for OS is frequently encountered, can persist for a significant time, and NP outcomes are similar in limb sparing and amputation groups.

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Synovial sarcoma presenting as colonic intussusception in a child

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