ClotAssist: A program to treat cancer-associated thrombosis in an outpatient pharmacy setting

Journal of Oncology Pharmacy Practice, Ahead of Print.


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In case of anastrozole-related hallucinations, can switching to letrozole be a treatment option? A case report and literature review

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Verapamil as a culprit of palbociclib toxicity

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Cilioretinal artery occlusion associated with cisplatin

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Comparison of the effectiveness of venous thromboembolism prophylaxis with enoxaparin between obese and non-obese patients

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Interstitial pneumonitis and myelosuppression associated to mitomycin C urinary tract instillations: A case report

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Using a treatment diary to improve the medication adherence in patients with chronic myeloid leukaemia

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Current status of drug vial optimization use to prevent waste associated with injectable anticancer agents

Journal of Oncology Pharmacy Practice, Ahead of Print.


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A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer – A real world experience

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Practice insights on patient care—management overview for chemoradiation toxic mucositis—guidelines, guideline-supported therapies and high potency polymerized cross-linked sucralfate (ProThelial)

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Malignant triton tumor of the duodenum: report of a case

Abstract

We report a case of malignant triton tumor of the duodenum, which is extremely rare. A submucosal malignant tumor was detected in the duodenum of a 49-year-old woman. The tumor was completely resected by performing pancreaticoduodenectomy. Pathological examination revealed that the lesion was a malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, i.e., a malignant triton tumor. Long-term survival has been achieved with no recurrence at 8.5 years after surgery.

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A cadaveric demonstration of visualization of the urethra using a lighted stent during transanal intersphincteric resection

Abstract

Urethral injury is one of the crucial intraoperative complications during transanal total mesorectal excision (taTME) for male patients with low rectal cancer. Urethral injury can occur during the anterior dissection around the inferior lobe of the prostate and the membranous urethra. A tool to visualize the urethra around this area would be useful to avoid urethral injury. We report a cadaveric demonstration of visualization of the urethra using a lighted stent during transanal intersphincteric resection. The lighted stent (InfraVision Ureteral Kit, Stryker) was placed through the irrigation channel of a clear three-way urinary catheter. After the anterior dissection, the visibility of the lighted stent was investigated under the three laparoscopic light conditions: (1) normal intensity; (2) low intensity; and (3) turned-off. In the proper dissection plane that led to preservation of the urethra, the lighted stent was hardly visible under the normal-intensity condition, but it was clearly visible under the turned-off condition. In the improper dissection plane that led to urethral injury, the lighted stent was clearly visible under both the normal-intensity and the turned-off conditions. Visualization of the urethra using the lighted stent under the turned-off condition of the laparoscopic light can be useful to avoid inadvertent urethral injury during the anterior dissection of male taTME. Clear visibility of the lighted stent under the normal-intensity condition can indicate that the dissection plane is too close to the urethra.

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Laparoscopic transhiatal lymphadenectomy in the lower mediastinum for adenocarcinoma of the esophagogastric junction

Abstract

Laparoscopic transhiatal esophagogastrectomy is difficult because the lower mediastinum is so deeply located that the operative field is narrow and restricted by surrounding organs. Therefore, we performed lymphadenectomy with opening of the bilateral mediastinal pleura to maintain safety and obtain better exposure of lymph nodes and important organs. We will present our technique for laparoscopic lower mediastinal lymphadenectomy and reconstruction for cancer of the esophagogastric junction. Five abdominal ports were used. Retraction of the left lobe of the liver exposed the esophageal hiatus. A long, narrow gastric tube (3 cm wide) was formed, and regional abdominal lymph nodes (No. 1, 2, 3a, 7, 8a, 9, 19, and 20) were resected. The diaphragmatic hiatus was widely split and the opened bilateral mediastinal pleura enabled better exposure for lymph node dissection and reconstruction. The level where the inferior vena cava passed through the diaphragm into the chest was used as a landmark to identify supradiaphragmatic (No. 111) and lower thoracic paraesophageal nodes (No. 110), which were completely retrieved with this procedure. The posterior mediastinal nodes (No. 112pulR, 112pulL, and 112aoA) were also retrieved with bilateral opening of the mediastinal pleura and dissection of the inferior pulmonary ligaments. An esophagogastric tube anastomosis with pseudo-fornix was made with a no-knife linear stapler to prevent postoperative reflux esophagitis. This approach enabled safe and accurate laparoscopic lower mediastinal nodal dissection. With the advantage of a narrow gastric tube, the good working space made tension-free anastomosis possible.

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Treatment and outcomes of 28 patients with spinal metastasis from gynecological cancer

Abstract

The aim of this study was to provide some useful information concerning clinical characteristics, surgical treatment, potential contributing factor and prognostic factors for patients with gynecological cancer (GC) spinal metastasis. We reviewed 28 patients with GC spinal metastasis in our spine tumor center between July 2008 and July 2015. Surgeries were performed on 22 of them. Univariate and multivariate analyses were conducted to identify potential prognostic factors affecting spinal metastasis-free survival (SMFS) and overall survival. The operative patients responded favorably according to decrease of VAS score and increase of Frankel grade after surgery. The 1- and 2-year survival rates in all patients were 60.7 and 41.0%, respectively. Univariate analysis suggested that age at diagnosis with GC was the potential contributing factor for spinal metastasis, while Frankel grade, ECOG-PS, visceral metastasis and chemotherapy were the potential prognostic factors affecting survival. Multivariate analysis indicated that the independent prognostic factors came from visceral metastasis and chemotherapy. Surgery played an important role in improving patients' quality of life. Patients over 50 years old had a shorter SMFS after diagnosed with GC. Visceral metastasis was an adverse prognostic factor for patients with GC spinal metastasis, while chemotherapy was a favorable one.

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Phase I/II trial of vorinostat, bevacizumab, and daily temozolomide for recurrent malignant gliomas

Abstract

Prognosis of recurrent glioblastoma (GBM) is poor with 6-month progression-free survival (PFS6) ranging from 9 to 48% depending on the treatment regimen and use of anti-angiogenic therapies. We sought to study vorinostat (VOR), a histone deacetylase inhibitor, in combination with bevacizumab (BEV) and daily metronomic temozolomide (TMZ) in a Phase I/II trial in recurrent high-grade gliomas (HGGs). This was a Phase I/II open-label, single-arm study in recurrent HGG patients. Phase I primary endpoint was to determine the maximum tolerated dose (MTD) of VOR with BEV and daily TMZ. Phase II primary endpoint was PFS6. Regimen was BEV 10 mg/kg iv every 2 weeks, TMZ 50 mg/m² po daily, and VOR 200 or 400 mg po alternating 7 days on then 7 days off throughout a 28-day cycle. Phase I portion enrolled nine subjects with three receiving VOR 200 mg and 6 receiving VOR 400 mg. With no dose-limiting toxicities (DLTs) at 200 mg and one DLT (thrombocytopenia, Grade 3) at 400 mg, the MTD was 400 mg. Phase II portion enrolled 39 GBM subjects, and PFS6 was 53.8% (95% CI 37.2–67.9%). Of note, 14 subjects had received prior BEV and all had received prior 5-day TMZ. Combination therapy with VOR, BEV, and daily TMZ was well tolerated and safe. While PFS6 was not statistically improved beyond historical controls, it is important to note that this was a heavily pretreated GBM population and further consideration is warranted in a less pretreated group.

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Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

Abstract

The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m² every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m² and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly higher frequency of thrombocytopenia (11.4% grade 3–4) compared to iri-bev (3.5% grade 3–4). Iri-bev patients had more gastrointestinal toxicity with regard to nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations of the study lom-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision in recurrent GBM therapy as efficacy is equal and no predictive factors for efficacy exist.

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The impact of a mind–body program on multiple dimensions of resiliency among geographically diverse patients with neurofibromatosis

Abstract

The neurofibromatoses (NF) are incurable genetic disorders that can cause nerve sheath tumors, chronic pain, and disfiguration. Patients with NF report lower quality of life and greater distress, and may benefit from programs that promote resiliency. To test effects of an 8-week mind–body program (Relaxation Response Resiliency Program for NF [3RP-NF]) on resiliency, using data derived from a larger randomized controlled trial of the 3RP-NF versus attention placebo control (Vranceanu et al. in Neurology 87:806–814, 2016). Participants (N = 63; 46 female; 52 White) were randomized to 3RP-NF (n = 32, M _age = 42.86) or control (n = 31, M _age = 39.90), completed intervention sessions via group videoconferencing, and provided self-report measures of resiliency (i.e., perceived coping abilities, perceived social support, gratitude, optimism, spiritual well-being, mindfulness) at baseline, post-intervention, and 6-month follow-up. All participants attended at least 6/8 sessions and 83% (N = 52) provided 6-month follow-up data. The 3RP-NF (vs. control) produced greater improvements from pre- to post-intervention in perceived coping abilities (M _difference = 6.68; p = .008), perceived social support (M _difference = 9.16; p = .032), and mindfulness (M _difference = 2.23; p = .035), which were maintained at 6-month follow up. We did not observe group differences in spiritual well-being, optimism, or gratitude. The 3RP-NF produced sustained increases in multiple dimensions of resiliency (perceived coping abilities, perceived social support, and mindfulness). Promoting resiliency may be particularly important for a population that is underserved and living with a chronic, incurable illness.

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Sex-dependent association of preoperative hematologic markers with glioma grade and progression

Abstract

Neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio, the systemic immune-inflammation index (SII), and red blood cell distribution width (RDW), have been recognized as promising predictors for histological grade and prognosis in multiple cancer types. However, few investigations illustrated the impacts of sex on the clinical utility of hematologic markers. Patients with primary gliomas were retrospectively reviewed. The association between grade and inflammatory markers by sex were investigated by univariate and multivariate analysis. The discrimination ability of logistic regression model was evaluated by the area under the receiver-operating characteristic curve (AUC) for high-grade glioma (HGG). Kaplan–Meier progressionfree survival (PFS) curves were plotted to assess the prognostic value of RDW. In subgroup analysis, distinctively elevated NLR and SII levels were exclusively present in male HGGs group (p = 0.001); whereas RDW notably increased in female HGGs group (p = 0.001). On multivariate analysis, increased odds ratio of HGGs was exclusively observed for female patients with elevated RDW (odds ratio = 1.589). Moreover, regression model developed by RDW exhibited an excellent discriminative ability for the prediction of HGGs in female patients (AUC = 0.817). Median progression time with RDW < 13.2 versus RDW ≥ 13.2 was 62.5 versus 33.0 months (log rank p = 0.017). Older females (≥ 45 years) with increased RDW levels portended worse survival (HR 3.693, 95% CI 1.747–8.325, p = 0.001). Meanwhile, the significant association of RDW levels with PFS in male subgroup was not observed (p > 0.05). In conclusion, superior to NLR and SII, RDW would be sex-specific predictor for tumor grade and progression for HGG female patients.

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Recursive partitioning analysis is predictive of overall survival for patients undergoing spine stereotactic radiosurgery

Abstract

Spine stereotactic radiosurgery (SRS) offers excellent radiographic and pain control for patients with spine metastases. We created a prognostic index using recursive partitioning analysis (RPA) to allow better patient selection for spine SRS. Patients who underwent single-fraction spine SRS for spine metastases were included. Primary histologies were divided into favorable (breast/prostate), radioresistant (renal cell/sarcoma/melanoma) and other. Cox proportional hazards regression was done to identify factors associated with overall survival (OS). RPA was performed to identify factors to classify patients into distinct risk groups with respect to OS. A total of 444 patients were eligible. Median dose was 16 Gy (range 8–18) in 1 fraction and median follow-up was 11.7 months. At time of analysis, 103 (23.1%) patients were alive. Median OS was 12.9 months. RPA identified three distinct classes. Class 1 was defined as KPS > 70 with controlled systemic disease (n = 142); class 3 was defined as KPS ≤ 70 and age < 54 years or KPS ≤ 70 age ≥ 54 years and presence of visceral metastases (n = 95); all remaining patients comprise class 2 (n = 207). Median overall survival was 26.7 months for class 1, 13.4 months for class 2, and 4.5 months for class 3 (p < 0.01). Our analysis demonstrates that there is considerably variability in survival among patients undergoing spine SRS. We created an objective risk stratification via RPA for spine SRS. Given the safety and efficacy of spine SRS and good survival in class 1 and 2 patients, this RPA can help clinicians identify patients who may benefit from upfront spine SRS.

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To drive or not to drive, that is still the question: current challenges in driving recommendations for patients with brain tumours

Abstract

Driving is a complex task that requires integration of various skills that may be impaired in patients with brain tumours. Determining fitness to drive is a responsibility of all physicians in Canada; however, it is an inconsistent practice based on few objective guidelines. The primary purpose of the study is to determine the consistency of driving recommendations amongst health care professionals in Ontario. Secondary aims include evaluation of physician awareness of driving regulations and determination of whether physicians would benefit from more specific driving guidelines. An 18-item questionnaire was sent to 126 health care professionals who take care of patients with brain tumours in Ontario. Seventy-five health care professionals responded to the survey. Less than 10% said they could reliably determine fitness to drive and almost an equal percentage of respondents indicated that determining fitness to drive should be a shared responsibility. The factors deemed important in determining driving safety were highly variable; 70% indicated that cognitive and emotional deficits were important. Over a third of respondents never heard of the CMA guidelines and of those who were familiar with it, 12.5% felt they were sufficient to inform clinical decisions. 90% of respondents wanted more specific and detailed driving guidelines for patients with brain tumours. The current guidelines for physicians are not specific enough for physicians to confidently determine fitness to drive in this population. These findings suggest the need for more detailed guidelines for driving safety that are based on empirical studies on driving habits and performance in patients with a variety of brain tumours.

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Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma

Abstract

Previous study revealed that higher expression of transforming growth factor beta induced (TGFBI) is correlated to poorer cancer-specific survival and higher proportion of tumor necrosis and Fuhrman grades III and IV in clear cell renal cell carcinomas. However, the relationships between TGFBI expression and malignant phenotypes of gliomas remain unclear. We downloaded and analyzed data from seven GEO datasets (GSE68848, GSE4290, GSE13041, GSE4271, GSE83300, GSE34824 and GSE84010), the TCGA database and the REMBRANDT database to investigate whether TGFBI could be a biomarker of glioma. From microarray data (GSE68848, GSE4290) and RNA-seq data (TCGA), TGFBI expression levels were observed to correlate positively with pathological grade, and TGFBI expression levels were significantly higher in gliomas than in normal brain tissues. Furthermore, in GSE13041, GSE4271 and the TCGA cohort, TGFBI expression in the mesenchymal (Mes) subtype high-grade glioma (HGG) was significantly higher than that in the proneural subtype. Kaplan–Meier survival analysis of GBM patients in the GSE83300 dataset, REMBRANDT and TCGA cohort revealed that patients in the top 50% TGFBI expression group survived for markedly shorter periods than those in the bottom 50%. Analysis of grade III gliomas showed that the median survival time was significantly shorter in the TGFBI high expression group than in the TGFBI low expression group. In addition, we found that TGFBI expression levels might relate to several classical molecular characterizations of glioma, such as, IDH mutation, TP53 mutation, EGFR amplification, etc. These results suggest that TGFBI expression positively correlates with glioma pathological grades and that TGFBI is a potential signature gene for Mes subtype HGG and a potential prognostic molecule.

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Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma

Abstract

Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor and involved in tumorigenesis of many cancers. However there are no reports on AHR in human meningioma. Therefore we examined the status of the AHR and its signalling molecules in human meningioma by using tumor biopsy samples and autopsy control meninges. We report the up regulation of AHR pathway genes like aryl hydrocarbon receptor nuclear translocator (ARNT), aldehyde dehydrogenase1family memberA3 (ALDH1A3), cytochrome P450, family1, subfamily A polypeptide1 (CYP1A1) and TCCD induced poly ADP ribose polymerase (TIPARP) gene expression in human meningioma. Further, AHR protein expression was found to be up regulated in all grades of human meningioma. We found that AHR localized in the nucleus for high grade anaplastic meningioma through immunohistochemical analysis. Since AHR signalling pathway was known to involve in inhibition of apoptosis in cancer cells, we evaluated the cyclophilin D levels which maintains mitochondrial permeability transition pore a critical event during apoptosis. We report that cyclophilin D levels were upregulated in all grades of human meningioma compared to control meninges. Finally we also evaluated c-Fos protein levels as its levels were regulated by AHR. Here we report that c-Fos protein levels were down regulated in all grades of human meningioma compared to control meninges. To sum-up we found that AHR signalling pathway components were upregulated, as the grade of the meningioma progresses from low to high grade, suggesting an important role of AHR signalling pathway in human meningioma.

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Analysis of immunobiologic markers in primary and recurrent glioblastoma

Abstract

Glioblastoma (GBM) generates a varied immune response and understanding the immune microenvironment may lead to novel immunotherapy treatments modalities. The goal of this study was to evaluate the expression of immunologic markers of potential clinical significance in primary versus recurrent GBM and assess the relationship between these markers and molecular characteristics of GBM. Human GBM samples were evaluated and analyzed with immunohistochemistry for multiple immunobiologic markers (CD3, CD8, FoxP3, CD68, CD163, PD1, PDL1, CTLA4, CD70). Immunoreactivity was analyzed using Aperio software. Degree of strong positive immunoreactivity within the tumor was compared to patient and tumor characteristics including age, gender, MGMT promoter methylation status, and ATRX, p53, and IDH1 mutation status. Additionally, the TCGA database was used to perform similar analysis of these factors in GBM using RNA-seq by expectation–maximization. Using odds ratios, IDH1 mutated GBM had statistically significant decreased expression of CD163 and CD70 and a trend for decreased PD1, CTLA4, and Foxp3. ATRX-mutated GBMs exhibited statistically significant increased CD3 immunoreactivity, while those with p53 mutations were found to have significantly increased CTLA4 immunoreactivity. The odds of having strong CD8 and CD68 reactivity was significantly less in MGMT methylated tumors. No significant difference was identified in any immune marker between the primary and recurrent GBM, nor was a significant change in immunoreactivity identified among age intervals. TCGA analysis corroborated findings related to the differential immune profile of IDH1 mutant, p53 mutant, and MGMT unmethylated tumors. Immunobiologic markers have greater association with the molecular characteristics of the tumor than with primary/recurrent status or age.

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Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG)

Abstract

Mixed reports leave uncertainty about whether normalization of apparent diffusion coefficient (ADC) to a within-subject white matter reference is necessary for assessment of tumor cellularity. We tested whether normalization improves the previously reported correlation of resection margin ADC with 15-month overall survival (OS) in HGG patients. Spin-echo echo-planar DWI was retrieved from 3 T MRI acquired between maximal resection and radiation in 37 adults with new-onset HGG (25 glioblastoma; 12 anaplastic astrocytoma). ADC maps were produced with the FSL DTIFIT tool (Oxford Centre for Functional MRI). 3 neuroradiologists manually selected regions of interest (ROI) in normal appearing white matter (NAWM) and in non-enhancing tumor (NT) < 2 cm from the margin of residual enhancing tumor or resection cavity. Normalized ADC (nADC) was computed as the ratio of absolute NT ADC to NAWM ADC. Reproducibility of nADC and absolute ADC among the readers' ROI was assessed using intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wCV). Correlations of ADC and nADC with OS were compared using receiver operating characteristics (ROC) analysis. A p value 0.05 was considered statistically significant. Both mean ADC and nADC differed significantly between patients subgrouped by 15-month OS (p = 0.0014 and 0.0073 respectively). wCV and ICC among the readers were similar for absolute and normalized ADC. In ROC analysis of correlation with OS, nADC did not perform significantly better than absolute ADC. Normalization does not significantly improve the correlation of absolute ADC with OS in HGG, suggesting that normalization is not necessary for clinical or research ADC analysis in HGG patients.

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Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol

Abstract

Epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT) promoter via methylation in a glioblastoma (GBM), has been correlated with a more favourable response to alkylating chemotherapeutic agents such as temozolomide. The use of global methylation surrogates such as Long Interspersed Nucleotide Element 1 (LINE1) may also be valuable in order to fully understand these highly heterogeneous tumours. In this study, we analysed both original and recurrent GBMs in 22 patients (i.e. 44 tumours), for both MGMT and LINE1 methylation status. In the 22 patients: 14 (63.6%) displayed MGMT methylation stability in the recurrent GBM versus 8 (36.4%), with instability of methylation status. No significant differences in overall and progression free survival was evident between these two groups. LINE1 methylation status remained stable for 12 (54.5%) of recurrent GBM patients versus 9 (41%) of the patients with instability in LINE1 methylation status (p = 0.02), resulting in an increase in overall survival of the stable LINE1 group (p = 0.04). The results obtained demonstrated major epigenetic instability of GBMs treated with temozolomide as part of the STUPP protocol. GBMs appear to undergo selective evolution post-treatment, and have the ability to recur with a newly reprogrammed epigenetic status. Selective targeting of the altered epigenomes in recurrent GBMs may facilitate the future development of both prognostic biomarkers and enhanced therapeutic strategies.

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Necrosis is a consistent factor to recurrence of meningiomas: should it be a stand-alone grading criterion for grade II meningioma?

Abstract

The purpose of this study was to evaluate spontaneous necrosis as a possible isolated factor for progression and recurrence in grade I meningiomas classified according to the current World Health Organization (WHO) classification. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The 2016 WHO classification of central nervous system tumors stratifies meningiomas in grades I (benign), II (atypical), and III (malignant), according to histopathological aspects and the risk of progression or recurrence. Among 110 patients with intracranial meningiomas, 70 were WHO grade I meningiomas with no findings of atypia (G1WON), 15 were WHO grade I with necrosis (G1WN), 21 were WHO grade II (G2), and 4 were WHO grade III (G3). The mean follow-up was 5.9 ± 0.2 years. High performance scale (KPS ≥ 80) was different (p < 0.001) between WHO grade I meningiomas without (81.4%) and with (60%) necrosis. The 5-year mortality rate was 1.4, 6.7 and 5.9% for G1WON, G1WN and G2, respectively, with significant difference (p = 0.011) related to the presence of necrosis. The risk of recurrence was 3.7 times higher in G1WN than in G1WON (p = 0.017), and 4.2 times in G2 (p = 0.010). Progression-free survival (PFS) was clearly higher in patients with G1WON compared to G1WN and G2 (p = 0.002 and p < 0.001, respectively). There was no significant difference in PFS between G1WN and G2 (p = 0.692). Retreatment was also superior in meningioma with necrosis. Our findings provide clear statistical data to consider that patients with benign meningiomas and histologic findings of spontaneous necrosis are at increased risk of progression and recurrence compared to those with benign lesion without atypical features. Statistical analysis curves also suggest that these lesions behave more similarly to those currently classified as WHO grade II meningioma.

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Update on the effect of exogenous hormone use on glioma risk in women: a meta-analysis of case-control and cohort studies

Abstract

Various studies have confirmed the important roles of endogenous hormones in the development of gliomas, while the roles of exogenous hormones remain controversial. Based on case-control studies and cohort studies, a meta-analysis was exerted to explore the effect of two exogenous hormones use (HRT: hormone replacement therapy; OC: oral contraceptives) on glioma risk. 16 eligible studies, including 11 case-control studies and 5 cohort studies, containing 8055027 women, were included in our study. All included studies have reported the relative risks (RRs) or odds ratios (ORs), and 95% confidence intervals (CIs). We use the fixed-effects model to calculate the estimated overall risk. In case-control studies, the risk of glioma was lower in women who had ever been treated with an exogenous hormone than in the control group (HRT: OR 0.91, 95% CI 0.84–0.99; OC: OR 0.99, 95% CI 0.91–1.07). In research of cohort studies, similar results have been obtained (HRT: RR 0.95, 95% CI 0.83–1.08; OC: RR 0.75, 95% CI 0.66–0.84). Our study further confirmed that the use of exogenous hormones has an important impact on the risk of glioma in women. However, more prospective studies are needed to further confirm this conclusion.

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Discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis

Abstract

When distant metastases are discovered, it is important to determine receptor profiles of these lesions through histologic examination. However, brain metastasis sites are difficult to reach to be routinely biopsied. The purpose of this study was to determine expression profiles of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer brain metastasis (BCBM) and the existence of discordance between primary breast cancer and brain metastasis. A total of 37 patients who underwent craniotomies for metastatic brain tumors arising from breast cancer at National Cancer Center (NCC) of Korea between 2002 and 2014 were retrospectively reviewed. Clinicopathologic data were collected from electronic medical records. Receptor profiles of primary breast cancer and brain metastasis in each patient were identified. Data of ER, PR, and HER2 expression in brain metastasis were available in electronic medical records for 21 (56.8%) of 37 cases. Results of ER, PR, and HER2 expression were positive in 47.6, 42.9, and 38.1% of patients with brain metastasis, respectively. Receptor conversion occurred in 11 (52.4%) of 21 patients (for ER, 9.5%; for PR, 38.1%; for HER2, 23.8%). Overall survival was longer in patients with concordant receptor expression patterns between primary breast cancer and brain lesion compared to that in patients with discordant patterns. However, such difference was not statistically significant (discordant vs. concordant median survival: 19.2 versus 31.1 months, p = 0.181). Receptor conversion in BCBMs was observed in over 50% of Korean patients used in this study. HER2 conversion was observed in 23.8% of patients in this study. Therefore, if resistance to anti-HER2 treatment is suspected in patients with BCBM, biopsy is needed to determine receptor profiles of brain lesion.

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PedsQL Neurofibromatosis Type 1 Module for children, adolescents and young adults: feasibility, reliability, and validity

Abstract

The objective of the present study was to report on the measurement properties of the Pediatric Quality of Life Inventory (PedsQL) Neurofibromatosis Type 1 Module for pediatric patients ages 5–25 from the perspectives of patients and parents. The 104-item PedsQL NF1 Module and 23-item PedsQL Generic Core Scales were completed in a multi-site national study by 323 patients and 335 parents (343 families). Patients were diagnosed with NF1 using the National Institutes of Health diagnostic criteria. In addition to a Total Scale Score, 18 unidimensional scales were derived measuring skin itch bother, skin sensations, pain, pain impact, pain management, cognitive functioning, speech, fine motor, balance, vision, perceived physical appearance, communication, worry, treatment anxiety, medicines, stomach discomfort, constipation, and diarrhea. The PedsQL NF1 Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.98; parent proxy-report α = 0.98), and good to excellent reliability for the 18 individual scales (patient self-report α = 0.71–0.96; parent proxy-report α = 0.73–0.98). Intercorrelations with the Generic Core Scales supported construct validity. Factor analysis supported the unidimensionality of the 18 individual scales. The PedsQL NF1 Module Scales demonstrated acceptable to excellent measurement properties, and may be utilized as standardized metrics to assess NF1-specific symptoms and problems in clinical research and practice in children, adolescents, and young adults.

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Clinical and dosimetric study of radiotherapy for glioblastoma: three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy

Abstract

Background and purpose

We aimed to compare three-dimensional conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) for the treatment of glioblastoma.

Materials and methods

Retrospective study of 220 patients with glioblastoma, treated with 3D-CRT or IMRT, with or without surgery. Dosimetric parameters as well as clinical and survival data for the two techniques were analyzed and compared.

Results

The median conformity index was 1.53 (range 0–2.69) for 3D-CRT and 1.25 (range 0.97–2.01) for IMRT, p < 10⁻⁴. The median homogeneity index was 0.10 (range 0.03–0.32) for 3D-CRT and 0.07 (range 0.03–0.18) for IMRT, p < 10⁻⁴. There were significantly fewer acute grade 1 and 2 neurological toxicities in the IMRT group especially for edema (1.3 versus 12.4%, p = 0.017), concentration disorders (6.6 versus 19.9%, p = 0.003) and consciousness disorders (2.6 versus 13.2%, p = 0.002) although IMRT patients had a significantly worse pre-treatment neurological status than 3D-CRT patients. Median survival was 16.0 months (range 11.9–17.8) for IMRT and 13.4 months (range 11.7–15.7) for 3D-CRT patients (p = 0.542).

Conclusion

IMRT improved target conformity and reduced neurological toxicities for patients with glioblastomas.

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Outcomes after second surgery for recurrent glioblastoma: a retrospective case–control study

Abstract

Studies looking at the benefit of surgery at first relapse (second surgery) for recurrent glioblastoma were confounded by including patients with varying grades of glioma, performance status and extent of resection. This case–controlled study aims to remove these confounders to assess the survival impact of second surgery in recurrent glioblastoma. Retrospective data on patients with glioblastoma recurrence at two tertiary Australian hospitals from July 2009 to April 2015 was reviewed. Patients who had surgery at recurrence were matched with those who did not undergo surgery at recurrence, based on the extent of their initial resection and age. Overall survival (OS1 assessed from initial diagnosis and OS2 from the date of recurrence) as well as functional outcomes after resection were analysed. There were 120 patients (60 in each institution); median age at diagnosis was 56 years. Median OS1 was 14 months (95% CI 11.5–15.7) versus 22 months (95% CI 18–25) in patients who did not undergo second surgery and those with surgery at recurrence. OS2 was improved by second surgery (4.7 vs 9.6, HR 0.52, 95% CI 0.38–0.72, P < 0.001), and by chemotherapy, given at recurrence, (HR 0.47, 95% CI 0.24–0.92, P = 0.03). After second surgery, 80% did not require rehabilitation and 61% were independently mobile. Second surgery for recurrent glioblastoma was associated with a survival advantage. Chemotherapy independent of surgery, also improved survival. Functional outcomes were encouraging. More research is required in the era of improved surgical techniques and new antineoplastic therapies.

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Tumor microenvironment after biodegradable BCNU wafer implantation: special consideration of immune system

Abstract

Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence. We investigated radiological imaging; the interval between the two surgeries; and immunohistochemistry of CD3, CD4, CD8, CD20, CD68, FOXP3, and PD1. We implanted BCNU wafers in 41 newly diagnosed glioblastoma patients after approval of the wafer in Japan. Of them, 14 underwent surgery at recurrence and tissue was obtained from around the wafers. The interval between the first and second surgeries ranged from 63 to 421 days. The wafer could be observed on magnetic resonance imaging at up to 226 days, whereas intraoperatively the biodegraded material of the wafer could be found at up to 421 days after the initial surgery. Immunohistochemical analysis demonstrated that CD8+ and CD68+ cells were significantly increased, but FOXP3+ cells did not increase, after wafer implantation compared to tissue from cases without wafer implantation. MRI data and immune cells, as well as interval between surgeries and immune cells, demonstrated positive correlation. These results helped us to understand the bioactivity of bioengineered materials and to establish a new approach for immunotherapy.

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Optimizing intrapleural bevacizumab dosing in non-small-cell lung cancer-mediated malignant pleural effusion: less is more

Future Oncology, Ahead of Print.


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Insights into the hepatocellular carcinoma patient journey: results of the first global quality of life survey

Future Oncology, Ahead of Print.


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Advances in immunotherapy for acute myeloid leukemia

Future Oncology, Ahead of Print.


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The role of IDH mutations in acute myeloid leukemia

Future Oncology, Ahead of Print.


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The use of alectinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small-cell lung cancer

Future Oncology, Ahead of Print.


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Overexpression of SLC7A11: a novel oncogene and an indicator of unfavorable prognosis for liver carcinoma

Future Oncology, Ahead of Print.


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Does sarcopenia affect outcome in patients with non-small-cell lung cancer harboring EGFR mutations?

Future Oncology, Ahead of Print.


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Comparison of primary breast cancer and paired metastases: biomarkers discordance influence on outcome and therapy

Future Oncology, Ahead of Print.


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Different inhibitors for the same target in metastatic luminal breast cancer: is there any difference?

Future Oncology, Ahead of Print.


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Utilization of radiotherapy and stereotactic body radiation therapy for renal cell cancer in the USA

Future Oncology, Ahead of Print.


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Triple negative breast cancer: are we scoring a home run?

Future Oncology, Ahead of Print.


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Do checkpoint inhibitors provide new hope for management of metastatic penile carcinoma?

Future Oncology, Ahead of Print.


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CD59: a promising target for tumor immunotherapy

Future Oncology, Ahead of Print.


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Biological imaging for individualized therapy in radiation oncology: part II medical and clinical aspects

Future Oncology, Ahead of Print.


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Biological imaging for individualized therapy in radiation oncology: part I physical and technical aspects

Future Oncology, Ahead of Print.


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MGMT pyrosequencing-based cut-off methylation level and clinical outcome in patients with glioblastoma multiforme

Future Oncology, Ahead of Print.


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miR-181a targets GATA6 to inhibit the progression of human laryngeal squamous cell carcinoma

Future Oncology, Ahead of Print.


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YB-1 promotes laryngeal squamous cell carcinoma progression by inducing miR-155 expression via c-Myb

Future Oncology, Ahead of Print.


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Correction to: Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

Correction to:

Strahlenther Onkol 2017

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Unfortunately, an incorrect reference was provided in Table 4.

The corrected version of Table 4 can be found below.

We apologize for any inconvenience …

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Wöchentliche oder dreiwöchentliche Cisplatin-Gaben bei der kombinierten Radiochemotherapie lokal fortgeschrittener Kopf-Hals-Tumoren?

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Cancer patients’ wish for psychological support during outpatient radiation therapy

Abstract

Background

Cancer patients frequently suffer from physical and psychosocial impairments due to their disease and its treatment. Psychooncology (PO) can help to cope with stress resulting from outpatient radiotherapy (RT) treatment. There are currently few data regarding patients' wishes for PO support. The aim of this study was to investigate the number of patients with a wish for PO, treatment paths, and predictors of the wish for PO among cancer patients at the beginning of RT.

Methods

The results of routine psychological stress screening (Hornheide screening instrument; cut-off  ≥ 4) of 944 cancer patients between 2015 and 2017 were analyzed in a retrospective cross-sectional study. Predictors for a wish for PO support were identified by stepwise binary logistic regression, in which sociodemographic and treatment data were included in addition to the screening items.

Results

Around 20% of patients had above-average stress levels and 13% expressed a wish for PO support (participation rate was approximately 55%). Low emotional wellbeing (OR = 11.3) and lack of social support (OR = 9.4) were strong predictors for this treatment wish. Among patients with pancreatic cancer, head and neck tumors, and hematologic disease, there was a substantial difference between the degree of psychological stress and the wish for treatment. Patients with urological (23.5%) and lung tumors (20.9%) most frequently expressed a wish for PO support.

Conclusion

Patient-reported psychosocial problems were better predictors of a wish for PO support than sociodemographic or clinical data. Stress screening should thus be implemented in clinical routine.

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Shorter treatment times reduce the impact of intra-fractional motion

Abstract

Purpose

To evaluate the impact of shorter treatment times on intra-fractional motion of the prostate during external beam radiotherapy.

Methods

53 h of intra-fractional motion of the prostate were recorded in real-time by 4D ultrasound (4DUS) during 720 fractions in 28 patients, 14 of which whom treated with step-and-shoot intensity-modulated radiotherapy (IMRT) and 14 of whom were treated with volumetric arc therapy (VMAT).

Results

The average VMAT fraction was recorded for 2 min 43 s and was substantially shorter than the average step-and-shoot IMRT fraction at 6 min 13 s. Average radial displacement of the prostate per fraction was substantially and significantly reduced from 1.31 ± 1.28 mm (n = 357 step-and-shoot IMRT fractions) to 0.96 ± 1.04 mm (n = 363 VMAT fractions), p = 0.00004. Radial, vertical, and longitudinal root-mean-square (r. m. s.) error per fraction was reduced from 1.55 to 1.12 mm (−28%, p < 0.0001), from 1.16 to 0.77 mm (−34%, p < 0.0001), and from 0.79 to 0.56 mm (−29%, p = 0.0002), respectively. Lateral intra-fractional motion was generally small and did not differ significantly. The prostate remained during 95% of fraction time within 4.55 mm of the isocenter in case of step-and-shoot IMRT and within 2.45 mm in case of VMAT. The variance of displacements increased linearly with time, and the rate was the same for both step-and-shoot IMRT and VMAT patients.

Conclusions

The position of the prostate changed less during shorter fractions, limiting fraction-average and end-of-fraction variance. This substantially and significantly reduced the impact of intra-fractional motion during shorter VMAT fractions as compared to longer step-and-shoot IMRT fractions.

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Intensity-modulated radiotherapy of prostate cancer with simultaneous integrated boost after molecular imaging with 18F-choline-PET/CT

Abstract

Purpose

To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB.

Methods

A total of 134 patients underwent intensity-modulated radiotherapy from 2007–2010. All patients received a total dose of 76 Gy with 2 Gy fractions to the prostate; 67 patients received an additional SIB of 80 Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire.

Results

Baseline characteristics were similar in both groups (prostate-specific antigen 11 ng/ml vs. 8 ng/ml, p = 0.20, Gleason score <6 in 36% vs. 46%, p = 0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5–6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, p = 0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, p = 0.17).

Conclusions

The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group.

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Lokale Metastasentherapie bei oligometatasierten Karzinomen

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Fallserie zur SBRT bei ventrikulärer Tachykardie zeigt beeindruckenden Therapieeffekt

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Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies

Abstract

Background

Radiotherapy (RT) has been known for decades as a local treatment modality for malign and benign disease. In order to efficiently exploit the therapeutic potential of RT, an understanding of the immune modulatory properties of ionizing radiation is mandatory. These should be used for improvement of radioimmunotherapies for cancer in particular.

Methods

We here summarize the latest research and review articles about immune modulatory properties of RT, with focus on radiation dose and on combination of RT with selected immunotherapies. Based on the knowledge of the manifold immune mechanisms that are triggered by RT, thought-provoking impulse for multimodal radioimmunotherapies is provided.

Results

It has become obvious that ionizing radiation induces various forms of cell death and associated processes via DNA damage initiation and triggering of cellular stress responses. Immunogenic cell death (ICD) is of special interest since it activates the immune system via release of danger signals and via direct activation of immune cells. While RT with higher single doses in particular induces ICD, RT with a lower dose is mainly responsible for immune cell recruitment and for attenuation of an existing inflammation. The counteracting immunosuppression emanating from tumor cells can be overcome by combining RT with selected immunotherapies such as immune checkpoint inhibition, TGF-β inhibitors, and boosting of immunity with vaccination.

Conclusion

In order to exploit the full power of RT and thereby develop efficient radioimmunotherapies, the dose per fraction used in RT protocols, the fractionation, the quality, and the quantity of certain immunotherapies need to be qualitatively and chronologically well-matched to the individual immune status of the patient.

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Durvalumab verbessert die Prognose beim lokal fortgeschrittenen nicht-kleinzelligen Bronchialkarzinom nach definitiver Radiochemotherapie

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Einfluss der prophylaktischen Ganzhirnbestrahlung auf das Gesamtüberleben beim fortgeschrittenen kleinzelligen Bronchialkarzinom

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Nachruf für Prof. Dr. med. Dr. hc. Wilhelm Oelßner, langjähriges Ehrenmitglied der DEGRO

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CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8 + T cells to Tc1 phenotype

Abstract

Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs. Here, we show that CD137L-DCs induce potent CD8⁺ T-cell responses against Epstein–Barr virus (EBV) and Hepatitis B virus (HBV), and that T cells primed by CD137L-DCs more effectively lyse EBV⁺ and HBV⁺ target cells. The chemokine profile of CD137L-DCs identifies them as inflammatory DCs, and they polarize CD8⁺ T cells to a Tc1 phenotype. Expression of exhaustion markers is reduced on T cells activated by CD137L-DCs. Furthermore, these T cells are metabolically more active and have a higher capacity to utilize glucose. CD137L-induced monocyte to DC differentiation leads to the formation of AIM2 inflammasome, with IL-1beta contributing to CD137L-DCs possessing a stronger T cell activation ability. CD137L-DCs are effective in crosspresentation. PGE2 as a maturation factor is required for enhancing migration of CD137L-DCs but does not significantly reduce their potency. This study shows that CD137L-DCs have a superior ability to activate T cells and to induce potent Tc1 responses against the cancer-causing viruses EBV and HBV which suggest CD137L-DCs as promising candidates for DC-based tumor immunotherapy.

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Adjuvant Bisphosphonate Therapy in Postmenopausal Breast Cancer

Opinion statement

Bone health and breast cancer are two connected subjects, because breast cancer patients have a higher prevalence of osteopenia/osteoporosis and reduced bone health parameters than healthy woman of the same age. Therefore, the positive effect of adjuvant bisphosphonate therapy plays an important role in breast cancer treatment. Several randomized trials have studied bisphosphonates in the adjuvant setting in postmenopausal woman and demonstrated their potential to prevent treatment-induced bone loss. The prevention of fractures and the subsequent preservation of patients' quality of life are important arguments for the use of adjuvant bisphosphonates in postmenopausal breast cancer patients. In addition, trials of adjuvant bone-targeted agents showed a reduction of recurrences in and outside bone and an improved outcome in patients treated with bisphosphonates.

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Systemic Treatment for Adults with Synovial Sarcoma

Opinion Statement

Synovial sarcoma (SS) is a rare, yet highly malignant, type of soft tissue sarcoma (STS), for which survival has not improved significantly during the past years. In this review, we focus on systemic treatment in adults. Compared to other STS, SS are relatively chemosensitive. Ifosfamide and ifosfamide combinations are active in different lines of treatment. In high-risk extremity and chest wall STS, neoadjuvant doxorubicin and ifosfamide has shown as much activity as high-dose ifosfamide. There are indications that combination chemotherapy with doxorubicin and ifosfamide in this setting improves outcome. In the first-line metastatic setting, combination treatment with doxorubicin and ifosfamide is a preferred option in fit patients, while in other patients, sequential doxorubicin and ifosfamide can be considered. In second and later lines, pazopanib and trabectedin have shown activity. Many new approaches to treat metastatic SS are currently under investigation, both preclinical as well as clinical, including other receptor tyrosine kinase inhibitors, epigenetic modulators, compounds interfering with DNA damage response (DDR), and immunotherapy.

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Enhanced expression of PD-1 and other activation markers by CD4+ T cells of young but not old patients with metastatic melanoma

Abstract

The biological behavior of melanoma is unfavorable in the elderly when compared to young subjects. We hypothesized that differences in T-cell responses might underlie the distinct behavior of melanoma in young and old melanoma patients. Therefore, we investigated the circulating T-cell compartment of 34 patients with metastatic melanoma and 42 controls, which were classified as either young or old. Absolute numbers of CD4+ T cells were decreased in young and old melanoma patients when compared to the age-matched control groups. Percentages of naive and memory CD4+ T cells were not different when comparing old melanoma patients to age-matched controls. Percentages of memory CD4+ T cells tended to be increased in young melanoma patients compared to young controls. Proportions of naive CD4+ T cells were lower in young patients than in age-matched controls, and actually comparable to those in old patients and controls. This was accompanied with increased percentages of memory CD4+ T cells expressing HLA-DR, Ki-67, and PD-1 in young melanoma patients in comparison to the age-matched controls, but not in old patients. Proportions of CD45RA−FOXP3^high memory regulatory T cells were increased in young and old melanoma patients when compared to their age-matched controls, whereas those of CD45RA+FOXP3^low naive regulatory T cells were similar. We observed no clear modulation of the circulating CD8+ T-cell repertoire in melanoma patients. In conclusion, we show that CD4+ T cells of young melanoma patients show signs of activation, whereas these signs are less clear in CD4+ T cells of old patients.

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Epithelioid Hemangioendothelioma: Update on Diagnosis and Treatment

Opinion statement

Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma, as such it can pose a clinical dilemma based solely on its rarity. Also, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. In our clinical practice, the primary focus has been to get a handle on the aggressive nature of the disease, which will then dictate how urgently one needs to treat the patient. Pathological review with immunohistochemistry and molecular characterization is paramount. Our treatment strategy is watch-and-wait versus active therapy on clinical trial or based on results of prior clinical trials. There is evidence to support the use of chemotherapeutics and targeted therapies specifically focusing on anti-angiogenesis. The current landscape of oncology with the emergence and excitement of immunotherapy could also translate in a role for immunotherapy in this disease. While rare, there is certainly no reason that research and trials for patients with EHE should not remain on utmost importance for those of us who specialize in the treatment of sarcomas.

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Testing the Timing: Time Factor in Radiation Treatment for Head and Neck Cancers

Opinion statement

Overall radiation treatment time has long been recognized as an important factor in head and neck tumor control. The concern of tumor growth in waiting time either before starting radiotherapy or during treatment is substantial given its negative impact on clinical outcome. There is an overwhelming evidence that increasing the time to initiate treatment increases the tumor burden and worsens the prognosis. This effect is more pronounced especially in patients with an early stage cancer disease. Delay in treatment initiation is contributed by both health care- and patient-related factors. Health care-related factors include advancement in diagnostic modalities and transfer of patient to academic health care centers accompanied by delayed referrals and long-awaited appointments. Patient-related factors include delayed reporting time and socioeconomic factors. An efficient transition of care along with access of cancer care modalities to community health care centers will not only improve the quality of care in secondary health care centers but also help decrease the patient burden in tertiary centers. A quick and well-structured multidisciplinary appointment program is fundamental in shortening the time required for patient referrals, thus increasing the optimal survival time for Head and Neck cancer patients with early initiation of treatment.

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When to Stop Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia

Opinion statement

Strict criteria for when to stop tyrosine kinase inhibitor (TKI) therapy in clinical practice are not easily defined without an agreement on what probability of achieving a treatment-free remission (TFR) constitutes a medically acceptable standard and consideration of the potential medical risks of continued TKI therapy and/or patient preferences. Patients in sustained deep molecular response (DMR) have no significant chronic myelogenous leukemia-related risk of progression and death, and thus, safety is of paramount importance. Patients with prior history of advanced disease, additional chromosomal abnormalities (ACA), atypical transcripts, TKI resistance, high Sokal score, or who cannot be relied upon to come for regular molecular monitoring should generally be excluded from TKI cessation in clinical practice. Similarly, stopping TKIs should not be attempted without the availability of standardized BCR-ABL1 testing with a sensitivity of at least MR4.5 and a turnaround time of less than 4 weeks. Prior TKI therapy of 5 years and stable MR4.0 of 2 years or more constitutes reasonable minimal criteria for stopping TKIs with approximately a 50% chance of success. The risk of morbidity with continued TKI therapy and patient preferences need to be considered to determine to what extent these minimal criteria should be exceeded and at what threshold to re-initiate therapy whether on the loss of major molecular response or at a lower molecular endpoint.

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Targeting the Tumor Microenvironment with Immunotherapy for Genitourinary Malignancies

Opinion statement

Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis. Despite this success, many patients fail to respond to immune checkpoint inhibitors and progression/relapse remains common. Furthermore, modest clinical activity has been observed with ICIs as a monotherapy in advanced PCa. As such, novel treatment approaches are warranted and improved biomarkers for patient selection and treatment response are desperately needed. Future efforts should focus on exploring synergistic and rational combinations that safely and effectively boost response rates and survival in genitourinary malignancies. Specific areas of interest include (1) evaluating the optimal sequencing, disease burden, and timing of immuno-oncology agents with other anti-cancer therapeutics and (2) validating novel biomarkers of response to immunotherapy to optimize patient selection and to identify individuals most likely to benefit from immunotherapy across the heterogenous spectrum of genitourinary malignancies.

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Current and Future Directions for Angiosarcoma Therapy

Opinion statement

Angiosarcomas are rare vascular neoplasms that are among the most aggressive subtypes of soft tissue sarcomas. Surgical resection is often challenging even in localized disease, as the infiltrative nature of these cancers leads to frequent local and metastatic recurrences. Cytotoxic chemotherapy, including anthracycline-based regimens and taxanes can produce significant responses in a subset of patients but durability is limited with most patients ultimately succumbing to metastatic disease. Targeted therapy with tyrosine kinase inhibitors is usually well-tolerated but prone to development of resistance. Few head-to-head trials have addressed the optimal sequence of therapies, or demonstrated conclusive benefits of one therapy over another based on clinical and etiologic factors. Novel therapies in clinical trials, including antibodies to endoglin and checkpoint inhibitors have demonstrated exciting early activity in patients with angiosarcoma. Improved understanding of the genetic heterogeneity within various angiosarcoma subtypes may identify predictive biomarkers to match patients to effective existing and future therapies. Overall, angiosarcoma patients with optimal performance status are best served in clinical trials that incorporate novel combinations of cytotoxic chemotherapy, targeted therapies, and immunotherapies.

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Polycythemia Vera

Opinion statement

Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN), the ultimate phenotype of the JAK2 V1617F mutation, the MPN with the highest incidence of thromboembolic complications, which usually occur early in the course of the disease, and the only MPN in which erythrocytosis occurs. The classical presentation of PV is characterized by erythrocytosis, leukocytosis, and thrombocytosis, often with splenomegaly and occasionally with myelofibrosis, but it can also present as isolated erythrocytosis with or without splenomegaly, isolated thrombocytosis or isolated leukocytosis, or any combination of these. When PV is present, the peripheral blood hematocrit (or hemoglobin) determination will not accurately represent the actual volume of red cells in the body, because in PV, in contrast to other disorders causing erythrocytosis, when the red cell mass increases, the plasma volume usually increases. In fact, unless the hematocrit is greater than 59%, true erythrocytosis cannot be distinguished from pseudoerythrocytosis due to plasma volume contraction. Usually, the presence of splenomegaly or leukocytosis or thrombocytosis establishes the diagnosis. However, when a patient presents with isolated thrombocytosis and a positive JAK2 V617F assay, particularly a young woman, the possibility of PV must always be considered because of plasma volume expansion. The WHO PV diagnostic guidelines are not helpful in this situation, since the hematocrit is invariably normal and a bone marrow examination will not distinguish ET from PV. Only a direct measurement of both the red cell mass and plasma volume can establish the correct diagnosis. In managing a PV patient, it is important to remember that PV is an indolent disorder in which life span is usually measured in decades, even when myelofibrosis is present, that chemotherapy is futile in eradicating the disease but does increase the incidence of acute leukemia and that hydroxyurea is not safe in this regard nor is it antithrombotic. Phlebotomy to a sex-specific normal hematocrit is the cornerstone of therapy and there now exist safe remedies for controlling leukocytosis, thrombocytosis, and extramedullary hematopoiesis and symptoms due to inflammatory cytokines when this is necessary.

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Accelerating Therapeutic Development through Innovative Trial Design in Colorectal Cancer

Opinion statement

Current trial design is challenged by the advancement of technologies that have enabled deeper understanding of the molecular drivers of colorectal cancer (CRC). The speed of trial testing and the ability to test larger volumes of promising novel agents in the face of smaller populations identified by molecular profiling are challenges posed to clinical studies. Master protocols that utilize umbrella designs are equipped to deal with potential biomarker and matched treatments simultaneously. Although complex in nature, they increase trial efficiency by utilizing shared screening platforms, test multiple treatments together, and simplify regulatory submission and reporting under a common protocol. Emerging technologies such as circulating tumor DNA (ctDNA) may help speed up adjuvant trials. These studies have been traditionally slow to complete due to low event rates and the high numbers needed to recruit. ctDNA used as a surrogate for minimal residual disease (MRD) and as an early marker of relapse may help counter some of these factors that deter innovation in this setting. Finally, in the era of precision medicine, surgery should not be forgotten as the only potentially curative option to date in metastatic disease. Five-year overall survival following resection of liver metastasis exceeds what can be achieved with chemotherapy alone in selected cases. Surgical advances have lowered morbidity and allow for greater resection volumes and repeated interventions. Although historically challenging, a well-designed randomized surgical intervention trial would greatly facilitate moving single-institution guidelines reported by case series into wider clinical practice.

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The Role of Circulating Tumor DNA in Renal Cell Carcinoma

Opinion statement

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a novel technology that can complement tumor tissue NGS and has the potential to influence diagnosis and treatment of both localized and metastatic renal cell carcinoma (mRCC). ctDNA NGS is an attractive alternative to tumor tissue NGS because it circumvents the need for repeated, invasive tissue biopsies while providing a contemporary mutational profile of a patient's tumors. While the role of ctDNA NGS in non-small cell lung cancer and colorectal cancer is well established, studies of ctDNA NGS in mRCC are only hypothesis-generating to date. In the localized RCC setting, ctDNA has demonstrated potential as a surveillance biomarker for disease recurrence. Earlier detection of mRCC, prior to the onset of symptoms, may lead to improved clinical outcomes. NGS of ctDNA in mRCC is even more promising in patients with metastatic disease. The majority of patients with mRCC have detectable ctDNA. Thus, ctDNA could be used to select patients for biomarker-guided clinical trials, such as savolitinib in MET-positive papillary RCC. Furthermore, studies have shown that the mutational profile of mRCC in ctDNA evolves after treatment progression. The most exciting potential role for ctDNA in mRCC is as a predictive biomarker for response to immunotherapy. Studies have shown that tumor mutational burden (TMB) is predictive of response to immune checkpoint inhibitors, and hypermutated ctDNA can act as a surrogate biomarker for TMB and response to immunotherapy. While studies of ctDNA in RCC are still in their infancy, there are many promising roles for ctDNA in localized and metastatic RCC.

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Quantifying tumor-infiltrating immune cells from transcriptomics data

Abstract

By exerting pro- and anti-tumorigenic actions, tumor-infiltrating immune cells can profoundly influence tumor progression, as well as the success of anti-cancer therapies. Therefore, the quantification of tumor-infiltrating immune cells holds the promise to unveil the multi-faceted role of the immune system in human cancers and its involvement in tumor escape mechanisms and response to therapy. Tumor-infiltrating immune cells can be quantified from RNA sequencing data of human tumors using bioinformatics approaches. In this review, we describe state-of-the-art computational methods for the quantification of immune cells from transcriptomics data and discuss the open challenges that must be addressed to accurately quantify immune infiltrates from RNA sequencing data of human bulk tumors.

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Cancer immunotherapy in patients with brain metastases

Abstract

The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain. Overall, these data provide encouraging evidence that these therapeutic agents can induce intracranial objective responses, particularly in patients with asymptomatic and previously untreated brain metastases. Larger prospective studies are needed to confirm these initial results.

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Rituximab as a therapeutic option for patients with advanced melanoma

Abstract

Treatment of metastatic melanoma remains challenging, despite a variety of new and promising immunotherapeutic and targeted approaches to therapy. New treatment options are still needed to improve long-term tumour control. We present a case series of seven patients with metastatic melanoma who were treated individually with the anti-CD20 antibody rituximab between July 2014 and July 2015. Two of the patients were treated in an adjuvant setting. All patients had already received a variety of treatments. During an induction phase, the administration of four cycles of weekly rituximab 375 mg/m² body surface area was planned. After imaging, patients with stable disease continued therapy with rituximab 375 mg/m² body surface area every 4 weeks up to a maximum of 24 weeks. Two patients experienced grade 2 infusion reactions during the first infusion. Otherwise, treatment was well tolerated and there were no grade 3 or 4 side effects. Staging after the induction phase showed stable disease in five patients, and two patients had progressive disease. Median progression-free survival was 6.3 months (95% CI 4.97–7.53), median overall survival was 14.7 months (95% CI 4.52–24.94), and one patient was still alive in December 2016. In conclusion, rituximab might be a therapeutic option for metastatic melanoma. However, further studies on rituximab among larger patient cohorts are warranted. Evaluation of therapy in an adjuvant setting or in combination with other systemic treatment might, therefore, be of particular interest.

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The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy

Abstract

Immunotherapy of non-small cell lung cancer (NSCLC), by immune checkpoint inhibitors, has profoundly improved the clinical management of advanced disease. However, only a fraction of patients respond and no effective predictive factors have been defined. Here, we discuss the prospects for identification of such predictors of response to immunotherapy, by fostering an in-depth analysis of the immune landscape of NSCLC. The emerging picture, from several recent studies, is that the immune contexture of NSCLC lesions is a complex and heterogeneous feature, as documented by analysis for frequency, phenotype and spatial distribution of innate and adaptive immune cells, and by characterization of functional status of inhibitory receptor⁺ T cells. The complexity of the immune landscape of NSCLC stems from the interaction of several factors, including tumor histology, molecular subtype, main oncogenic drivers, nonsynonymous mutational load, tumor aneuploidy, clonal heterogeneity and tumor evolution, as well as the process of epithelial–mesenchymal transition. All these factors contribute to shape NSCLC immune profiles that have clear prognostic significance. An integrated analysis of the immune and molecular profile of the neoplastic lesions may allow to define the potential predictive role of the immune landscape for response to immunotherapy.

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Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers

Abstract

Purpose

It is now recognized that solid tumors encroach on the host's immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T-cell population against tumors have been met with limited clinical success. We aimed to devise a two-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, thereby determining treatment efficacy.

Experimental design

Treatment commenced with the acquisition of whole tumor antigens from tumor cell lines corresponding with patients' primary malignancy. Lysate mixture was inoculated intradermally, while peripheral blood mononuclear cells (PBMCs) were periodically extracted via phlebotomy and expanded in culture ex vivo for re-infusion. Post-treatment tumor-specific T-cell response and cytotoxicity was confirmed via Elispot and real-time cell analyzing (RTCA) assay. Serum cytokine levels and cytotoxicity scores were evaluated for associations with survival status and duration.

Results

There was a significant increase in cytotoxicity exhibited by T cells measured using both Elispot and RTCA following treatment. Correlation analysis determined significant association between higher post-treatment cytotoxicity scores and survival status (R = 0.52, p = 0.0028) as well as longer survival duration in months (R = 0.59, p = 0.005).

Conclusions

Our treatment protocol successfully demonstrated significant correlation between tumor-associated antigen-specific immune response and objective prolongation of survival. Whole-cell cancer antigen priming and adoptive T-cell therapy is, therefore, a highly feasible clinical model which can be easily replicated to positively influence outcome in end-stage malignancy.

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T-cell receptor-β V and J usage, in combination with particular HLA class I and class II alleles, correlates with cancer survival patterns

Abstract

Class I and class II HLA proteins, respectively, have been associated with subsets of V(D)J usage resulting from recombination of the T-cell receptor (TCR) genes. Additionally, particular HLA alleles, in combination with dominant TCR V(D)J recombinations, have been associated with several autoimmune diseases. The recovery of TCR recombination reads from tumor specimen exome files has allowed rapid and extensive assessments of V(D)J usage, likely for cancer resident T-cells, across relatively large cancer datasets. The results from this approach, in this report, have permitted an extensive alignment of TCR-β VDJ usage and HLA class I and II alleles. Results indicate the correlation of both better and worse cancer survival rates with particular TCR-β, V and J usage-HLA allele combinations, with differences in median survival times ranging from 7 to 130 months, depending on the cancer and the specific TCR-β V and J usage/HLA class allele combination.

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Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines

Abstract

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Prostate inflammation and carcinoma are associated with high levels of myeloid cell infiltration; these cells are linked to disease progression in other cancers, but their role in prostate cancer is unclear. To determine whether myeloid cells contribute to prostate cancer progression, the ability of prostate tumor-associated CD11b⁺ cells (TAMC) to drive prostate epithelial cell tumorigenesis was tested. Co-culture of CD11b⁺ TAMC with non-tumorigenic genetically primed prostate epithelial cells resulted in stable transformation and induction of tumorigenesis. RNA sequencing identified the IL-1α pathway as a potential molecular mechanism responsible for tumor promotion by TAMC. Inhibition of IL-1α delayed growth of TAMC-induced tumors. Further analysis showed that IL-1α inhibition led to decreased angiogenesis within tumors, suggesting that IL-1α promotes prostate tumor progression, potentially through augmentation of angiogenesis.

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Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy

Abstract

The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. The most prominent finding was an immediate and significant (p < 0.05) decrease of lymphocyte proliferation and interferon-γ production directly after therapy which lasted until day 28 and was stronger upon stimulation with microbial antigens than with mitogens. Moreover, lymphopenia was revealed, affecting all lymphocyte subsets (CD3+, CD4+, CD8+ T cells, CD4+ CD8+ T cells, B cells and NK cells). SIRT led to a reduction in the percentage of activated HLA-DR+ monocytes and of CD45R0+ memory T cells. Higher radiation activity, the presence of liver cirrhosis, chronic kidney disease, diabetes mellitus and metastases were unfavorable factors for immunocompetence, while a better Eastern Cooperative Oncology Group performance status was associated with stronger immunological reactions. In conclusion, SIRT leads to severe impairment of cellular in vitro immune responses. Further studies are needed to assess a potential clinical impact.

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Recurrent Pneumonia due to Fibrosing Mediastinitis in a Teenage Girl: A Case Report with Long-Term Follow-Up

A teenage girl was evaluated for recurrent right pneumonia. The evaluation revealed a calcified mediastinal mass that compressed the right intermediate and middle lobar bronchi, as well as the right pulmonary artery and veins. The clinical picture together with imaging studies and borderline positive serology testing suggested a diagnosis of fibrosing mediastinitis associated with histoplasmosis. This rare condition is characterized by the local proliferation of invasive fibrous tissue within the mediastinum due to a hyperimmune reaction to Histoplasma capsulatum. Antifungal and anti-inflammatory therapies are usually ineffective, and surgical intervention contains a high morbidity risk. Palliative surgery and stenting of the compressed airway have been suggested. In the past, the prognosis was thought to be poor, but recent studies demonstrate a more positive outcome. Our patient had been radiologically and functionally stable under follow-up for over thirteen years and has married and delivered two healthy children, both following an uneventful pregnancy.

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Erratum: Behandlung im Voraus planen – Bedeutung für die Intensiv- und Notfallmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: e1-e1
DOI: 10.1055/a-0591-7094

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

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Psycho-Oncology, Volume 27, Issue S2, Page 9-22, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 9-22, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 28-28, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 28-28, March 2018.


http://ift.tt/2DANPBA

Psycho-Oncology, Volume 27, Issue S2, Page 3-8, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 3-8, March 2018.


http://ift.tt/2FXza8X

Psycho-Oncology, Volume 27, Issue S2, Page 26-27, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 26-27, March 2018.


http://ift.tt/2tUJuK5

Psycho-Oncology, Volume 27, Issue S2, Page 29-30, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 29-30, March 2018.


http://ift.tt/2G2Pq8w

Psycho-Oncology, Volume 27, Issue S2, Page 1-2, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 1-2, March 2018.


http://ift.tt/2tX0YFp

Psycho-Oncology, Volume 27, Issue S2, Page 23-25, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 23-25, March 2018.


http://ift.tt/2G3W5PS

Psycho-Oncology, Volume 27, Issue S2, Page 28-28, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 28-28, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 29-30, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 29-30, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 9-22, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 9-22, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 3-8, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 3-8, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 26-27, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 26-27, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 1-2, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 1-2, March 2018.


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Psycho-Oncology, Volume 27, Issue S2, Page 23-25, March 2018.

Psycho-Oncology, Volume 27, Issue S2, Page 23-25, March 2018.


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The interplay of reactive oxygen species and the epidermal growth factor receptor in tumor progression and drug resistance

The epidermal growth factor receptor (EGFR) plays important roles in cell survival, growth, differentiation, and tumorigenesis. Dysregulation of the EGFR is a common mechanism in cancer progression especially ...

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Workplace experiences and turnover intention among adult survivors of childhood cancer

Abstract

Purpose

The purpose of this study was to investigate workplace experiences and turnover intention (consideration of leaving or changing a job) and to examine factors associated with turnover intention among survivors.

Methods

Adult survivors of childhood cancer with a history of employment (n = 289) completed measures of workplace experiences (n = 50, 18–29 years; n = 183, 30–44 years; n = 56; > 45 years of age at follow-up). Turnover intention was assessed using three items from the Job Satisfaction Scale. Responses were dichotomized as reflecting high vs. low turnover intention. Path analysis was used to estimate the influence of demographic characteristics, treatment exposures (cranial radiation therapy [CRT]), and workplace experiences on turnover intention.

Results

Thirty percent of survivors reported high turnover intention (95% CL, 25 to 36%). Exposure to CRT (P = 0.003), older attained age (P < 0.001), experiencing formal workplace discrimination (P = 0.008), and having lower continuance (P < 0.001) or affective commitment (P < 0.001) were associated with high turnover intention among survivors. Informal discrimination, mediated through job satisfaction, also influenced survivors' reported intent to leave their jobs.

Conclusions

One third of adult survivors of childhood cancer report turnover intention, which is related to their cancer treatment, but more temporally proximal, workplace discrimination. Additional research is needed to understand the consequences of turnover intention among survivors.

Implications for Cancer Survivors

Survivors and their health care providers should be aware of legislative policies related to workplace discrimination (e.g., American with Disabilities Act) and related implications for job turnover.

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Workplace experiences and turnover intention among adult survivors of childhood cancer

Abstract

Purpose

The purpose of this study was to investigate workplace experiences and turnover intention (consideration of leaving or changing a job) and to examine factors associated with turnover intention among survivors.

Methods

Adult survivors of childhood cancer with a history of employment (n = 289) completed measures of workplace experiences (n = 50, 18–29 years; n = 183, 30–44 years; n = 56; > 45 years of age at follow-up). Turnover intention was assessed using three items from the Job Satisfaction Scale. Responses were dichotomized as reflecting high vs. low turnover intention. Path analysis was used to estimate the influence of demographic characteristics, treatment exposures (cranial radiation therapy [CRT]), and workplace experiences on turnover intention.

Results

Thirty percent of survivors reported high turnover intention (95% CL, 25 to 36%). Exposure to CRT (P = 0.003), older attained age (P < 0.001), experiencing formal workplace discrimination (P = 0.008), and having lower continuance (P < 0.001) or affective commitment (P < 0.001) were associated with high turnover intention among survivors. Informal discrimination, mediated through job satisfaction, also influenced survivors' reported intent to leave their jobs.

Conclusions

One third of adult survivors of childhood cancer report turnover intention, which is related to their cancer treatment, but more temporally proximal, workplace discrimination. Additional research is needed to understand the consequences of turnover intention among survivors.

Implications for Cancer Survivors

Survivors and their health care providers should be aware of legislative policies related to workplace discrimination (e.g., American with Disabilities Act) and related implications for job turnover.

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Aeromonas caviae mimicking Vibrio cholerae infectious enteropathy in a cholera-endemic region with possible public health consequences: two case reports

Aeromonas species have been documented to yield false positive results in microbiological tests for Vibrio cholerae. They share many biochemical properties with Vibrio species, with which they were jointly classi...

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Adding value within medicine’s new paradigm: the pediatric radiologist

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Utilizing clinical pathways and web-based conferences to improve quality of care in a large integrated network using breast cancer radiation therapy as the model

Clinical pathways outline criteria for dose homogeneity and critical organ dosimetry. Based upon an internal audit showing suboptimal compliance with dosimetric parameters in whole breast irradiation (WBI), we...

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Adding value within medicine’s new paradigm: the pediatric radiologist

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Utilizing clinical pathways and web-based conferences to improve quality of care in a large integrated network using breast cancer radiation therapy as the model

Clinical pathways outline criteria for dose homogeneity and critical organ dosimetry. Based upon an internal audit showing suboptimal compliance with dosimetric parameters in whole breast irradiation (WBI), we...

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Allogeneic Stem Cell Transplantation for Relapsed Primary Central Nervous System Lymphoma: Is it feasible?

Publication date: Available online 16 March 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Erden Atilla, Ugur Sahin, Pinar Ataca Atilla, Mustafa Merter, Elif Ozyurek, Koray Ceyhan, Sinem Civriz Bozdag
Primary central nervous system lymphoma (PCNSL), has an aggressive course and in untreated patients median survival is limited to three months. For relapsed PCNSL, the treatment options are few and results are usually unsatisfactory. Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) has been widely used for treatment of relapsed/refractory NHL patients. However there are limited data whether graft versus lymphoma effect can work in PCNSL patients. Here, we present a relapsed refractory PCNSL case treated by allo-HCT.



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Survival differences in childhood and young adult acute myeloid leukemia: A cross-national study using US and England data

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Sherlly Xie, Md Jobayer Hossain
BackgroundAcute myeloid leukemia (AML) is a serious disease with complex etiology and marked variation in survival. Known prognostic factors include AML subtypes, age at diagnosis and sex. However, survival outcomes may vary across healthcare systems. In this study, we evaluated the survival patterns in individuals diagnosed with AML at ages 0–24 years in the US and England between prognostic features and across countries.MethodsWe obtained data on 4387 and 2194 subjects from the US Surveillance Epidemiology and End Result registries and UK National Cancer Data Repository. Subjects were diagnosed and followed in 1995–2014. Kaplan-Meier curve and stratified Cox proportional hazards regression were used in the analysis.ResultsOverall risk of mortality was 23% lower in English patients compared to that in the US patients (adjusted hazard ratio (aHR), 95% confidence Interval (CI): 0.77, 0.71–0.84). Survival difference of similar extent was observed in subgroups of sex and age at diagnosis. However, mortality risks between two countries varied substantially across AML subtypes, especially in AML inv(16) (1.81, 0.61–5.34), AML with minimal differentiation (0.54, 0.25–1.17), AML without maturation (0.38, 0.20–0.74) and AML with maturation (0.52, 0.31–0.86).ConclusionsSimilar to the population trend, mortality risk across sex, age at diagnosis, and most AML subtypes was lower in England. Survival outcome for AML with and without maturation in England was better than the population trend, while that for AML inv(16) was worse. Our findings suggest that future etiologic and policy research may uncover the underlying mechanisms and contribute to closing these morality gaps.



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Circulating inflammatory proteins and gallbladder cancer: Potential for risk stratification to improve prioritization for cholecystectomy in high-risk regions

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Jill Koshiol, Yu-Tang Gao, Amanda Corbel, Troy J. Kemp, Ming-Chang Shen, Allan Hildesheim, Ann W. Hsing, Asif Rashid, Bingsheng Wang, Ruth M. Pfeiffer, Ligia A. Pinto
BackgroundInflammatory proteins could help identify individuals most likely to have gallbladder cancer (GBC) among those waiting for cholecystectomy.MethodsWe analyzed 49 circulating inflammation-related proteins in 144 patients with GBC and 150 patients with gallstones. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs for protein quantiles and GBC versus gallstones. Using proteins associated with early GBC (stage 1–2) that were selected in stepwise logistic regression, we created an inflammation score and explored the potential utility for risk stratification.Results26 proteins (53%) had P values for the trend across categories ≤0.001, with associations for a one category increase ranging from 1.52 (95% CI: 1.20–1.94) for CC motif ligand 4 to 4.00 (95% CI: 2.76–5.79) for interleukin (IL)-8. Soluble tumor necrosis factor receptor 2 (sTNFR2), IL-6, sTNFR1, CC motif ligand 20 (CCL20), vascular cell adhesion molecule 1, IL-16, and granulocyte colony-stimulating factor had P values ≤0.001 for early GBC. Of those, IL-6, IL-16, CCL20, and STNFR1 were included in the inflammation score. In a high-risk setting with a pre-test disease risk of 10% (e.g., elderly patients) and using an inflammation score cutoff that provides 90% sensitivity, 39% of patients on the waiting list would be predicted to be positive, and 23% of those would be predicted to have GBC.ConclusionThese results highlight the strong associations of inflammatory proteins with GBC risk and their potential clinical utility. Larger studies are needed to identify the most effective combinations of inflammatory proteins for detecting early GBC and precursor lesions.



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Survival differences in childhood and young adult acute myeloid leukemia: A cross-national study using US and England data

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Sherlly Xie, Md Jobayer Hossain
BackgroundAcute myeloid leukemia (AML) is a serious disease with complex etiology and marked variation in survival. Known prognostic factors include AML subtypes, age at diagnosis and sex. However, survival outcomes may vary across healthcare systems. In this study, we evaluated the survival patterns in individuals diagnosed with AML at ages 0–24 years in the US and England between prognostic features and across countries.MethodsWe obtained data on 4387 and 2194 subjects from the US Surveillance Epidemiology and End Result registries and UK National Cancer Data Repository. Subjects were diagnosed and followed in 1995–2014. Kaplan-Meier curve and stratified Cox proportional hazards regression were used in the analysis.ResultsOverall risk of mortality was 23% lower in English patients compared to that in the US patients (adjusted hazard ratio (aHR), 95% confidence Interval (CI): 0.77, 0.71–0.84). Survival difference of similar extent was observed in subgroups of sex and age at diagnosis. However, mortality risks between two countries varied substantially across AML subtypes, especially in AML inv(16) (1.81, 0.61–5.34), AML with minimal differentiation (0.54, 0.25–1.17), AML without maturation (0.38, 0.20–0.74) and AML with maturation (0.52, 0.31–0.86).ConclusionsSimilar to the population trend, mortality risk across sex, age at diagnosis, and most AML subtypes was lower in England. Survival outcome for AML with and without maturation in England was better than the population trend, while that for AML inv(16) was worse. Our findings suggest that future etiologic and policy research may uncover the underlying mechanisms and contribute to closing these morality gaps.



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