Τετάρτη 26 Οκτωβρίου 2016

A phase II trial of concurrent chemoradiotherapy with weekly docetaxel plus cisplatin treatment for unresectable locally advanced head and neck cancer

Although concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN), the optimal CCRT regimen is not yet defined. We conducted a phase II study of weekly docetaxel and cisplatin treatment with concurrent radiotherapy (RT) to investigate the efficacy and toxicity profiles.

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Analysis of risk factors for pulmonary complications in patients with limited-stage small cell lung cancer

Abstract

Introduction

The most effective therapy in patients with limited-stage small cell lung cancer (LS SCLC) seems to be chemotherapy (using platinum-based regimens) and thoracic radiotherapy (TRT), which is followed by prophylactic cranial irradiation.

Materials and methods

The analysed group comprised 217 patients who received combined treatment for LS SCLC, i.e. chemotherapy (according to cisplatin and etoposide schedule) and TRT (concurrent in 101 and sequential in 116 patients). The influence of chemoradiotherapy (ChT-RT) schedule on treatment results (frequency of complete response, survival rates, and incidence of treatment failure and complications) was evaluated, and the frequency and severity of pulmonary complications were analysed to identify risk factors.

Results

The 5‑year survival rates in concurrent vs. sequential ChT-RT schedules were 27.3 vs. 11.7% (overall) and 28 vs. 14.3% (disease-free). The frequencies of adverse events in relation to concurrent vs. sequential therapy were 85.1 vs. 9.5% (haematological complications) and 58.4 vs. 38.8% (pulmonary fibrosis), respectively. It was found that concurrent ChT-RT (hazard ratio, HR 2.75), a total dose equal to or more than 54 Gy (HR 2.55), the presence of haematological complications (HR 1.89) and a lung volume receiving a dose equal to or greater than 20 Gy exceeding 31% (HR 1.06) were the risk factors for pulmonary complications.

Conclusion

Pulmonary complications after ChT-RT developed in 82% of patients treated for LS SCLC. In comparison to the sequential approach, concurrent ChT-RT had a positive effect on treatment outcome. However, this is a factor that can impair treatment tolerance, which manifests in the appearance of side effects.



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AREG triggered EGFR activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by EGFR inhibitors

Abstract

Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement. The resistant cells did not have the secondary ALK mutations frequently occurring in crizotinib-resistant cells, and these cells were cross-resistant to alectinib and ceritinib as well. In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model. Cell clone #2 did not have an EGFR mutation, but the expression of amphiregulin (AREG), one of EGFR ligands, was significantly increased. A knockdown of AREG with small interfering RNAs restored the sensitivity to crizotinib. These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.

This article is protected by copyright. All rights reserved.



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A phase ΙI clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study

Summary

We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily OS, PFS, RR, DCR and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (p=0.023, p=0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (p=0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.

This article is protected by copyright. All rights reserved.



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VEGF promoter-based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma

Abstract

Malignant mesothelioma (MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma (MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM. We constructed a vascular endothelial growth factor promoter-based conditionally replicative adenovirus (VEGF-CRAd) that replicates exclusively in VEGF-expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA, and VEGF-CRAd selectively replicated in these MM cells and exerted a direct concentration-dependent oncolytic effect in vitro. Furthermore, our in vivo studies showed that pre-infection of MM cells with VEGF-CRAd potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF-CRAd prolonged the survival time of tumor-bearing mice. Our results indicate that VEGF-CRAd exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF-CRAd is safe and might represent a promising therapeutic strategy for MPM.

This article is protected by copyright. All rights reserved.



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AREG triggered EGFR activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by EGFR inhibitors

Abstract

Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement. The resistant cells did not have the secondary ALK mutations frequently occurring in crizotinib-resistant cells, and these cells were cross-resistant to alectinib and ceritinib as well. In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model. Cell clone #2 did not have an EGFR mutation, but the expression of amphiregulin (AREG), one of EGFR ligands, was significantly increased. A knockdown of AREG with small interfering RNAs restored the sensitivity to crizotinib. These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.

This article is protected by copyright. All rights reserved.



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A phase ΙI clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study

Summary

We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily OS, PFS, RR, DCR and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (p=0.023, p=0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (p=0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.

This article is protected by copyright. All rights reserved.



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VEGF promoter-based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma

Abstract

Malignant mesothelioma (MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma (MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM. We constructed a vascular endothelial growth factor promoter-based conditionally replicative adenovirus (VEGF-CRAd) that replicates exclusively in VEGF-expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA, and VEGF-CRAd selectively replicated in these MM cells and exerted a direct concentration-dependent oncolytic effect in vitro. Furthermore, our in vivo studies showed that pre-infection of MM cells with VEGF-CRAd potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF-CRAd prolonged the survival time of tumor-bearing mice. Our results indicate that VEGF-CRAd exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF-CRAd is safe and might represent a promising therapeutic strategy for MPM.

This article is protected by copyright. All rights reserved.



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Endocarditis and monocular blindness

A man aged 77 years with postrenal transplant lymphoproliferative disease was admitted with high fever, elevated inflammatory markers and a heart murmur. Blood cultures grew Enterococcus faecalis and he was found to have mitral valve endocarditis on echocardiogram and subsequently started on appropriate antibiotics. 5 days into treatment, he developed ocular symptoms and 3 days later, he had irreversible monocular visual loss. He was seen by the ophthalmology team who diagnosed endogenous endopthalmitis secondary to bacteraemic spread from his endocarditis. Despite treatment with intravitreal antibiotics and prolonged systemic antibiotics, his sight did not recover. Although septic emboli are common in endocarditis, endogenous endophthalmitis is rarely reported and frequently results in visual loss. Early treatment confers an improved prognosis.



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Amyloidosis: an unusual cause of upper gastrointestinal bleeding

We report a rare case of upper gastrointestinal bleeding in a 55-year-old man with monoclonal gammopathy of unknown significance presenting with abdominal pain, weight loss and melaena. Gastroscopy was unremarkable, but melaena persisted, with the development of symptomatic anaemia. While colonoscopy excluded a lower gastrointestinal aetiology, CT revealed jejunitis, confirmed at capsule endoscopy. Histopathological examination of specimens obtained at single balloon enteroscopy revealed an unusual aetiology: small bowel AL-amyloidosis. We review his clinical presentation, radiological, endoscopic and histological findings and review the literature of this unusual condition.



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Systemic sarcoidosis first manifesting in a tattoo in the setting of immune checkpoint inhibition

The use of immune checkpoint inhibitors is revolutionising the treatment of cancer. However, their unique toxicity profile is substantially different from what has been observed with traditional chemotherapy, resulting in a novel learning curve for medical oncologists. Early recognition of these toxicities can make a substantial impact in ameliorating these side effects in the oncological and medical–surgical fields. Here, we present a case of Lofgren syndrome sarcoidosis, which first manifested in a tattoo in a patient with metastatic urothelial cancer on therapy with anti-CTLA-4 (ipilimumab) and anti-PD1 (nivolumab).



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Commonly forgotten complication of Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) is a frequently encountered condition in clinical practice and management is generally uncomplicated with patients on a stable dose of thyroxine supplementation. However, complications of thyroid lymphoma can develop, though it is rare and hence commonly forgotten by physicians. We present a case of a patient with HT who developed thyroid lymphoma. A 61-year-old woman presented with an enlarged goitre complicated by compressive symptoms and was diagnosed with HT. She was treated with stable dose of thyroxine but her constitutional symptoms of weight loss prompted further investigations and diagnosis of diffuse large B-cell lymphoma was eventually made. She underwent chemotherapy and adjuvant radiotherapy and is currently in remission 1 year post-treatment. There should be an increased index of suspicion of primary thyroid lymphoma in patients with HT for early diagnosis and treatment for better outcomes.



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Young man with sudden severe hip pain secondary to femoral neck stress fracture

Femoral neck stress fractures have been described in military recruits and athletes. Early recognition and aggressive treatment are important, as femoral neck stress fractures have a high potential for complications and even uncomplicated fractures require an extensive course of rehabilitation. Tension-side (superolateral) stress fractures of the femoral neck are at high risk for complications such as displacement, non-union and avascular necrosis, and need to be treated surgically, while compression-side (inferomedial) fractures can be treated conservatively. We describe a case illustrating a typical presentation of insidious hip pain culminating in sudden onset of severe hip pain in a healthy young man. We perform a literature review of studies showing epidemiology, treatment algorithms and rehabilitation.



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Disseminated pilomyxoid astrocytoma in infancy with novel MUTYH mutation

Description

A 3-month-old girl presented with 5 days of abnormal eye movements. Neurological examination was significant for axial hypotonia. MRI of the brain revealed extensive T2 prolongation and enhancement within the optic chiasm, optic nerves, bilateral basal ganglia, cerebellum and temporal lobes (figure 1). MRI of the spine showed extensive enhancement along the cervicomedullary junction and cervical and thoracic cord consistent with leptomeningeal metastatic disease (figure 2). The patient underwent right frontotemporal craniotomy for debulking of the tumour and biopsy. Neuropathology revealed a moderately cellular tumour with uniform nuclei, small amounts of myxoid material and perivascular clearing consistent with pilomyxoid astrocytoma (PMA) (figure 3). Molecular analysis demonstrated a novel MUTYH Y165C mutation. The patient died 17 months after diagnosis despite multimodal chemotherapy regimens due to disease progression.

Figure 1

T2-weighted axial (A, B), sagittal (C) and coronal (D) MRI of the brain shows...



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Takotsubo cardiomyopathy with severe bradyarrhythmia following epidural insertion

We present a case of takotsubo cardiomyopathy (TTC) with ventricular stand still and atrioventricular block. TTC can mimic ST elevation myocardial infarction and heart failure, but in this case resulted in a severe cardiac conduction disorder and ventricular standstill. This is a recognised but unusual presentation and serves as a lesson to those undertaking anaesthetics to be vigilant for TTC.



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Bilateral primary adrenal lymphoma with adrenal insufficiency

Primary adrenal lymphoma is an extremely rare condition. We describe a case of bilateral adrenal lymphoma in a man aged 55 years who was admitted to our hospital. He had a 3-month history of left flank pain, nausea and vomiting with weight loss. A CT scan at a private hospital revealed bilateral large adrenal masses; the patient was referred to our centre based on these findings. He was evaluated for pheochromocytoma by an endocrinology team; however, all findings were negative. In addition, a cosyntropin stimulation test indicated adrenal insufficiency. A Trucut biopsy of the adrenal gland revealed diffuse large B-cell lymphoma of the adrenal glands, and the patient responded extremely well to chemotherapy.



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Cotrimoxazole treats fluoroquinolone-resistant Salmonella typhi H58 infection

A woman aged 20 years presented with fever and no localising signs. She was treated with cotrimoxazole and the subsequent blood culture was positive for Salmonella typhi (S. typhi), which was resistant to fluoroquinolones but susceptible to cotrimoxazole. Genotyping identified an FQ-R subclade of H58 S. typhi. Fever clearance time was 4 days after starting the antibiotics, and no relapses were noted on 2 months of follow-up. This inexpensive, well-known and easily available antimicrobial could be suitably redeployed for fluoroquinolone-resistant enteric fever in South Asia.



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Primary hepatic Burkitt's lymphoma as first manifestation of HIV-AIDS in a hepatitis B seropositive adult: when defences fail

Description

A previously well 32-year-old heterosexual man presented with progressive wasting syndrome, jaundice, night sweats, vomiting and abdominal pain for 1 month. There was no history of recreational drug use or exposure to hepatotoxins. Examination showed normal vital signs, a body mass index of 18 kg/m2, generalised muscle atrophy, oral thrush and no lymphadenopathy with an enlarged liver 14 cm below the costal margin at the midclavicular line. The physical examination was otherwise normal.

Serology for HIV enzyme-linked immune sorbent assay (ELISA), Western blot immunoassay tests and hepatitis B surface antigen were all seropositive confirming new onset HIV–AIDS with hepatitis B coinfection. Extensive investigations for other diseases were negative and relevant results are shown (table 1). The HIV viral load was high at 300 392 RNA copies/mL and the CD4+ T-cell count was low at 116 cells/µL (reference values 410–1590). Serum creatinine was also high at 4.2 mg/dL and blood urea...



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Crizotinib in ROS1 rearranged non-small cell lung cancer (NSCLC), from response to resistance

We examined an immediate, but short-lived, response to crizotinib, a drug with a new indication for ROS1 rearranged non-small cell lung cancer (NSCLC) in a middle-aged non-smoker. The patient presented with metastatic NSCLC and extensive disease in multiple organs. He was treated with crizotinib 250 mg twice a day. Within 2–3 days, his condition rapidly improved, which was evident in a CT scan 2 months later. However, after 3 months of treatment, his condition deteriorated dramatically. The patient did not respond to ceritinib, a second-line drug that targets anaplastic lymphoma kinase, and died shortly after. This case demonstrated an impressive but brief response to crizotinib.



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Invasive thymoma presenting as classic superior vena cava syndrome: a case of venous spread metastasis

The approach to an intrinsic cause of superior vena cava syndrome (SVCS) is usually difficult but rewarding. We report a case of a middle-aged man who presented with progressive oedema of the upper half of the body, dyspnoea, cough and weight loss for a 1-year duration. He was a non-smoker without prior hospitalisation. Chest radiography showed right-sided pleural effusion with an apparent normal superior mediastinum. Contrast-enhanced CT of the chest revealed a right atrial mass extending and completely obliterating to superior vena cava. The differentials were tuberculosis, invasive fungal granuloma, sarcoidosis, primary vasculitis, chronic venous thrombosis, cardiac sarcoma/lymphoma and metastatic thyroid tumour or thymoma. He underwent transvenous (femoral approach) biopsy of the mass and then cardiothoracic surgery after haemodynamic instability. Pathology showed invasive thymoma type B3. This case highlights the approach to an intrinsic cause of SVCS, a complication of the transvenous approach, and importantly a noble finding of venous spread metastasis.



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Resolution of left ventricular postinfarction thrombi in patients undergoing percutaneous coronary intervention using rivaroxaban in addition to dual antiplatelet therapy

Left ventricular (LV) thrombus is usually seen in situations with reduced LV function, and is mostly seen in patients with large anterior ST-elevation myocardial infarction (MI). Most embolic events, in patients with LV thrombus formation, occur within the first 3–4 months, thus the recommendations regarding the duration of anticoagulant therapy. According to guidelines, an oral vitamin K antagonist, warfarin, is being used as an anticoagulant for this period. Novel oral anticoagulants were found to be either non-inferior or superior compared with warfarin in prevention of thromboembolism in patients with non-valvular atrial fibrillation. However, the data about their role in the management of LV thrombus are limited to case reports. Here, we report on the dissolution of LV apical thrombus in 3 patients with anterior ST-elevation MI receiving dual antiplatelet therapy and rivaroxaban on a reduced dose for 3 months.



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Phaeochromocytoma presenting as an acute coronary syndrome

A 44-year-old Caucasian man presented to the emergency department in acute cardiogenic shock, with pulmonary oedema, secondary to an acute myocardial infarction and in a hyperosmolar hyperglycaemic state. The previous day he had undergone a colonoscopy, which revealed features of colitis, and was started on prednisolone. He had been previously diagnosed with type 2 diabetes, migraine and anxiety attacks. While awaiting a coronary angiogram he developed abdominal pain and a CT scan was performed and found a large right adrenal mass. Plasma-free metadrenaline levels were elevated. After 4 months, a right adrenalectomy was performed successfully. He made a good recovery with normalisation of his heart function and resolution of his diabetes. The diagnosis was delayed for years due to his episodic symptoms being attributed to other more common diagnoses. Although a rare diagnosis in itself, there are case reports of phaeochromocytoma initially presenting with an acute coronary syndrome.



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Unequal cancer survivorship care: addressing cultural and sociodemographic disparities in the clinic

Abstract

The number of individuals diagnosed with cancer is growing worldwide. Cancer patients from underserved populations have widely documented disparities through the continuum of cancer care. As the number of cancer survivors (i.e., individuals who have completed cancer treatment) from underserved populations also continue to grow, these individuals may continue to experience barriers to survivorship care, resulting in persistent long-term negative impacts on health and quality of life. In addition, there is limited participation of survivors from underserved populations in clinical trials and other research studies. To address disparities and change practices in survivorship care, a better understanding of the roles of both socioeconomic status (SES) and of culture in cancer care disparities and the relevance of these to providing high-quality care is needed. SES and culture often overlap but are not identical; understanding the impact of each is especially relevant to survivorship care. To enhance health equity among cancer survivors, clinicians need to practice culturally competent care, address cultural beliefs and practices that may influence survivors' beliefs and activities, gain awareness of historical patterns of medical care in the survivor's community, and consider how barriers to cross-cultural communications may hinder communication in clinical settings. While the design and implementation of survivorship care programs emphasizing effectiveness and equity is complex and potentially time consuming, it is critical for providing optimal care for all survivors, including those from the most vulnerable populations.



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Outcome and late effects among acute myeloid leukemia survivors: a nationwide population-based study

Abstract

Background

Understanding of pathogenesis and treatment for acute myeloid leukemia (AML) is growing. However, studies regarding the outcomes and late effects among AML survivors are relatively limited.

Methods

This nationwide population-based study used medical records from the Taiwanese National Health Insurance Research Database. A total of 3356 AML patients diagnosed from 2000 to 2008 were analyzed. The physiological and psychological morbidities in AML survivors were compared to those identified from a normal population. This study also compared late effects among AML survivors treated by intensive chemotherapy alone and allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Results

The incidence of AML in Taiwan has increased from 1.07 per 100,000 persons in 2000 to 2.17 per 100,000 persons in 2008 (p < 0.0001). With the median overall survival (OS) time of 0.98 years, 25.0 % of AML patients in this study cohort received best supportive care alone. Compared to the normal population, AML survivors had higher rates of hypertension (hazard ratio [HR] 1.69; 95 % confidence interval [CI] 1.18–2.42; p < 0.01), cardiovascular disease (HR 2.53; 95 % CI 1.39–4.61; p < 0.01), diabetes (HR 2.27; 95 % CI 1.48–3.48; p < 0.001), and psychological disorders (HR 1.45; 95 % CI 1.04–2.04; p < 0.05). Although patients undergoing allo-HSCT had a better OS than did patients treated with intensive chemotherapy alone (median not reached vs. 1.53 years; p < 0.0001), diabetes was found more often among allo-HSCT recipients than among patients receiving intensive chemotherapy only (HR 2.93; 95 % CI 1.21–7.08; p < 0.05).

Conclusion

Regular physical and psychological surveillance of AML survivors is needed especially for those receiving allo-HSCT.



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Managing neutropenia by pegfilgrastim in patients affected by relapsed/refractory multiple myeloma treated with bendamustine-bortezomib-dexamethasone



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Randomized controlled trial of supportive-expressive group therapy and body-mind-spirit intervention for Chinese non-metastatic breast cancer patients

Abstract

Purpose

This study aimed to evaluate the efficacy of supportive-expressive group (SEG) therapy and body-mind-spirit (BMS) intervention on emotional suppression and psychological distress in Chinese breast cancer patients.

Methods

This three-arm randomized controlled trial assigned 157 non-metastatic breast cancer patients to BMS, SEG, or social support control group. SEG focused on emotional expression and group support, whereas BMS emphasized relaxation and self-care. All groups received 2-h weekly sessions for 8 weeks. The participants completed measurements on emotional suppression, perceived stress, anxiety, and depression at baseline and three follow-up assessments in 1 year.

Results

Using latent growth modeling, overall group difference was found for emotional suppression (χ 2(2) = 8.88, p = 0.012), marginally for perceived stress (χ 2(2) = 5.70, p = 0.058), but not for anxiety and depression (χ 2(2) = 0.19–0.94, p > 0.05). Post-hoc analyses revealed a significant and moderate reduction (Cohen d = 0.55, p = 0.007) in emotional suppression in SEG compared to control group, whereas BMS resulted in a marginally significant and moderate fall (d = 0.46, p = 0.024) in perceived stress. Neither SEG nor BMS significantly improved anxiety and depression (d < 0.20, p > 0.05).

Conclusions

The present results did not demonstrate overall effectiveness for either BMS or SEG therapy in the present sample of Chinese non-metastatic breast cancer patients. The participants appear to derive only modest benefits in terms of their psychological well-being from either intervention.



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Classification of painful bone metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and EORTC QLQ-BM22

Abstract

Purpose

Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes.

Methods

We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA).

Results

The two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1–5, 6, and 7–10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain.

Conclusion

Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1–5 as mild pain, 6 as moderate pain, and 7–10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.



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Acupuncture for treating hot flashes in breast cancer patients: an updated meta-analysis

Abstract

Purpose

The aim of this study was to evaluate the effectiveness of acupuncture for treatment of hot flash in women with breast cancer.

Methods

The aspects considered in this study included searching for 12 data bases until April 2015 and consulting reference lists of reviews and related articles. Additional features studied comprised all articles on human patients with breast cancer treated with needle acupuncture with or without electrical stimulation for the treatment of hot flashes. The methodological quality was assessed using the modified Jadad score.

Result

The searches identified 12 relevant articles for inclusion. The meta-analysis without any subgroup or moderator failed to show favorable effects of acupuncture on reducing the frequency of hot flashes after intervention (n = 680, SMD = − 0.478, 95 % CI −0.397 to 0.241, P = 0.632) but exhibited marked heterogeneity of the results (Q value = 83.200, P = 0.000, I^2 = 83.17, τ^2 = 0.310).

Conclusion

The meta-analysis used had contradictory results and yielded no convincing evidence to suggest that acupuncture was an effective treatment of hot flash in patients with breast cancer. Multi-central studies including large sample size are required to investigate the efficiency of acupuncture for treating hot flash in patients with breast cancer.



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Safety, efficacy, and patient-perceived satisfaction of peripherally inserted central catheters in terminally ill cancer patients: a prospective multicenter observational study

Abstract

Purpose

The purpose of this study was to investigate the safety, efficacy, and subjective satisfaction of peripherally inserted central catheters (PICCs) in terminally ill cancer patients.

Methods

All PICCs were inserted by an interventional radiologist with radiological guidance. We monitored the occurrence of PICC-related complication and evaluated the patient-perceived satisfaction for PICC using semi-structured questionnaire.

Results

A total of 36 terminally ill cancer patients underwent PICC. Three patients had 2 PICC insertions; hence, finally 39 episodes during 829 PICC days were analyzed. All procedures were completed without any procedure-related complication. The median catheter life span was 19.0 days (95 % CI, 14.1–23.9). Thirty-four cases maintained the PICC until the intended time, while the other 5 cases (12.8 %; 6.1/1000 PICC days) were premature PICC removals. Totally 10 complications (25.6 %; 12.3/1000 PICC days) were reported including premature removals (n = 5), trivial bleedings (n = 3), and thrombophlebitis (n = 2). Patients reported that the procedure was not distressing (42 %), a little distressing (36 %), or distressing (21 %). Of 30 patients who had preserved cognitive function at fifth day, most patients (n = 25, 83 %) reported more comfort although the other 5 patients reported no change (n = 3) or less comfort (n = 2).

Conclusions

PICCs were safely inserted and showed favorable maintenance rate with acceptable complications. Additionally, most of the patients felt that parenteral access became much comfortable after PICC insertion. When considering the characteristics of terminally ill cancer patients, poor general condition and a limited period of survival, PICC could be a safe and effective method for intravenous access.



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“Melanoma: Questions and Answers.” Development and evaluation of a psycho-educational resource for people with a history of melanoma

Abstract

Purpose

People with melanoma often report pervasive fears about cancer recurrence, unmet information needs, and difficulties accessing psychological care. Interventions addressing the supportive care needs of people with melanoma are rare, and needs are often overlooked. The study evaluated a newly developed, evidence-based, psycho-educational resource for people with melanoma.

Methods

The evaluation study comprised three groups: adults at high risk of new primary disease due to multiple previous melanomas or one melanoma and dysplastic nevus syndrome (DNS), adults at moderate risk due to one previous melanoma and no DNS, and health professionals involved in melanoma care. Participants evaluated a 68-page psycho-educational booklet, Melanoma: Questions and Answers, developed by a multidisciplinary team in accordance with published evidence, clinical guidelines, and intervention development frameworks. The booklet comprised seven modules featuring information on melanoma diagnosis, treatment, prognosis, and ongoing clinical management; risk factors and the role of genetic counseling services for melanoma; psycho-education on emotional, behavioral, and cognitive responses to melanoma, including psycho-education on fear of cancer recurrence; description of healthy coping responses; a suite of tailored tools to support skin self-examination, doctor-patient communication, and identification of the signs and symptoms of anxiety and depression; a list of community-based services and resources; and tools to support melanoma-related record keeping and monitoring. Resource acceptability, relevance, quality, dissemination preferences, emotional responses, unmet information needs, and demographic characteristics were assessed.

Results

Nineteen melanoma survivors (response rate 50 %) and 10 health professionals (response rate 83 %) evaluated the resource. Responses were overwhelmingly positive; the booklet was thoroughly read and highly rated in terms of quality and quantity of information, utility of health education tools, and capacity to address unmet needs. Ninety-five percent of melanoma survivors would recommend the booklet to others. Most preferred a paper-based format, provided by their treating doctor at diagnosis.

Conclusions

Melanoma: Questions and Answers was feasible and acceptable and demonstrated a strong capacity to address the information and psycho-educational needs of people with melanoma at low fiscal cost.



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Cost savings of home bortezomib injection in patients with multiple myeloma treated by a combination care in Outpatient Hospital and Hospital care at Home

Abstract

At home injectable chemotherapy for patients receiving treatment for hematological diseases is still in debate. Given the expense of new innovative medicines, at home treatment has been proposed as a suitable option for improving patient quality of life and decreasing treatment costs. We decided to assess the cost of bortezomib administration in France among multiple myeloma patients from an economic standpoint. Patients in this study were treated within a regional hematological network combining outpatient hospital care and Hospital care at Home administration. To make the cost comparison, our team simulated outpatient hospital care expenses. Fifty-four consecutive multiple myeloma patients who received at least one injection of bortezomib in Hospital care at Home from January 2009 to December 2011 were included in the study. The median number of injections was 12 (range 1–44) at home and 6 (range 0–30) in the outpatient care unit. When compared with the cost simulation of outpatient hospital care alone, bortezomib administration with combined care was significantly less expensive for the National Health Insurance (NHI) budget. The mean total cost per patient and per injection was 954.20 € for combined outpatient and Hospital care at Home vs 1143.42 € for outpatient hospital care alone. This resulted in an estimated 16.5 % cost saving (Wilcoxon signed-rank test, p < 0.0001). The greatest savings were observed in administration costs (37.5 % less) and transportation costs (68.1 % less). This study reflects results for a regionally implemented program for multiple myeloma patients treated with bortezomib in routine practice in a large rural area.



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A nurse-led protocol improves the time to first dose intravenous antibiotics in septic patients post chemotherapy

Abstract

Purpose

Neutropenic sepsis is a time-dependent emergency with early interventions shown to improve outcomes. Broad spectrum intravenous antibiotic administration is the initial therapy in patients with suspected neutropenic sepsis. Compliance with early antibiotic administration in febrile neutropenia patients is poor. Innovations have been trialled to improve the time to first dose intravenous antibiotics in patients with suspected neutropenic sepsis. Consideration of extending first dose intravenous antibiotic prescribing to trained nursing staff may improve performance in this key standard.

Methods

A retrospective analysis was performed at a specialist oncology hospital in the North West of England from January 1st 2015 to January 31st 2016. The nurses on the Medical Admissions Unit (MAU) have been given the responsibility of assessing patients presenting with fever post chemotherapy including prescribing and administering the first dose of intravenous antibiotics with the aim of improving the speed of this intervention.

Results

During the study period, 697 patients presented to the MAU with suspected sepsis post chemotherapy. Six hundred seventy-two (96.4 %) patients received their first dose of intravenous antibiotics within 60 min of presentation to the MAU. Of this group, 323 (48.1 %) were administered antibiotics within 15 min of arrival. Of the 25 (3.6 %) patients who did not receive antibiotics within 1 h, root cause analysis revealed the reason in 23 (92 %) patients was an inability to ascertain intravenous access.

Conclusion

Nurse-led protocols are an effective, safe, and sustainable method for achieving early antibiotic administration in patients with suspected febrile neutropenia. This is a key component of ensuring improved outcomes for this cohort of patients.



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Evaluation of the perceptions and cosmetic satisfaction of breast cancer patients undergoing totally implantable vascular access device (TIVAD) placement

Abstract

Purpose

Totally implantable vascular access devices (TIVADs) are widely used to administer chemotherapy to cancer patients. While great progress has been made with respect to breast surgical reconstruction to take into account both aesthetics and patients' perceptions of body integrity, these aspects have not been considered with regard to the impact of TIVAD. In order to address this practice gap, we have adapted our TIVAD implantation technique to improve cosmetic results. The aim of this study was to assess breast cancer patients' comfort level and aesthetic satisfaction with regard to TIVAD insertion.

Methods

Patients with breast cancer admitted for chemotherapy at an outpatient clinic completed a previously validated survey evaluating three main domains: symptoms (pain, discomfort) related to the TIVAD itself in daily activity, information received before and during the surgical procedure, and cosmetic aspects regarding the port insertion site (scar, port, and catheter location).

Results

Between September 2010 and June 2011, 232 patients were evaluated. Cosmetic satisfaction with scar location was high (93.3 %). Information given to patients before and during the procedure had a major impact on both symptom perception in daily activity and on cosmetic satisfaction.

Conclusions

Obtaining a more aesthetic scar by placing the TIVAD in the deltopectoral groove contributed to a high rate of cosmetic satisfaction. Furthermore, the relevance of information given to patients before and/or during surgery had a major impact on symptom perception. Therefore, we suggest including a pre-operative information session in the care pathway.



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Multidrug infusions in a Swiss palliative care unit: assessment of frequent combinations in terms of clinical effectiveness, compatibility, and stability

Abstract

Purpose

The objectives of this study were to trace, monitor, and assess for clinical effectiveness, visual compatibility, and stability of commonly used combinations of drugs for patients hospitalized in a Swiss palliative care unit, over a 12-month period.

Methods

In this longitudinal analysis, commonly used multidrug combinations were monitored with a duly created data collection sheet for healthcare professionals. Assessment of visual changes of the mixtures and the evaluation of major changes in the overall symptom control over time were recorded. The clinical changes were classified according to reasonable correlation to the modality of drug administration and not to clinical evolution of the underlying disease.

Results

Over a 12-month period, a total of 48 multidrug infusions were recorded and monitored. The infusions were composed of two, three, four, or five active principles. Infusions were given over a 24-h period, mainly intravenously, either through an implantable venous access port or a peripheral venous access. Main diluent was normal saline solution. Commonly used drug combinations included morphine and haloperidol, morphine, haloperidol and octreotide, morphine, haloperidol, octreotide, and chlorpromazine. No precipitations were observed during the study. Patients maintained a clinical stability and no salient changes in symptom control were attributed to inefficacy of the multidrug infusions.

Conclusions

The use of multidrug infusions for parenteral administration appears to confirm an adequate visual compatibility and stability, while maintaining effectiveness in terms of overall symptom control.



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An audit of acute oncology services: patient experiences of admission procedures and staff utilisation of a new telephone triage system

Abstract

Objectives

In 2010, St. James Institute of Oncology (Leeds, UK) created a new acute oncology service (AOS) consisting of a new admissions unit with a nurse-led telephone triage (TT) system. This audit cycle (March 2011 and June 2013) evaluated patient experiences of the reconfigured AOS and staff use of the TT system.

Methods

Patient views were elicited via a questionnaire and semi-structured interviews. The TT forms were analysed descriptively evaluating completion and data quality, reported symptoms and their severity and advice given (including admission rates).

Results

Patients (n = 40) reported high satisfaction with the new AOS. However, 56 % of patients delayed 2 days or more before contacting the unit. In 2011, 26 % of all the admitted patients were triaged via the TT system; 133 TT forms were completed. In June 2013, 49 % of the admitted patients were triaged; 264 forms were completed. The most commonly reported symptoms on the TT forms were pain, pyrexia/rigors/infection, diarrhoea, vomiting and dyspnoea. Half of the patients using the TT system were admitted (52 % in 2011, 49 % in 2013).

Conclusions

Our audit provided evidence of successful implementation of the TT system with the number of TT forms doubling from 2011 to 2013. The new AOS was endorsed by patients, with the majority satisfied with the care they received.



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Experiences of colorectal cancer patients in the 2-years post-diagnosis and patient factors predicting poor outcome

Abstract

Purpose

There are few recent longitudinal studies investigating the quality of life of colorectal cancer patients in the early years following diagnosis. This study aimed to (i) compare the health status of people with colorectal cancer less than 1 year from diagnosis with health status 1 year later and (ii) determine the characteristics associated with a change in overall health status.

Methods

The study was conducted as part of a larger trial. Participants (n = 539) were identified via the Victorian Cancer Registry in Australia, completed a computer-assisted baseline telephone interview (including the EQ-5D-3L) within 6–12 months of diagnosis, and mailed a survey 12 months later.

Results

At baseline, the majority of participants (55 %) reported some problems, including difficulties in usual activities (26 %), pain or discomfort (25 %), anxiety or depression (23 %) and mobility issues (15 %). Sixty-nine percent had either an unchanged or increased health utility score from baseline to follow-up. The largest proportion reporting an increase in problems between baseline and follow-up related to pain or discomfort (18 %). While visual analogue scale scores indicated a significantly improved health state over time overall, 32 % reported a decreased health utility score from baseline to follow-up. Those aged over 80 years were more likely to report a decreased health utility score compared to 60–80-year-olds.

Conclusions

A sizeable minority of patients experience ongoing problems in their daily lives and should be offered assistance in overcoming disabilities and returning to best possible functioning, particularly older patients who appear to be vulnerable to poor outcomes.



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Efficacy and safety of lipegfilgrastim compared with placebo in patients with non-small cell lung cancer receiving chemotherapy: post hoc analysis of elderly versus younger patients

Abstract

Purpose

Lipegfilgrastim, a glycoPEGylated recombinant granulocyte colony-stimulating factor (G-CSF), reduces neutropenia duration and febrile neutropenia (FN) incidence in patients with cancer receiving myelosuppressive chemotherapy. A phase 3 trial of lipegfilgrastim was conducted in patients with advanced non-small cell lung cancer (NSCLC) receiving cisplatin/etoposide (which produces mild-to-moderate myelosuppression). Because patients aged >65 years are at higher risk for FN versus younger patients, this post hoc analysis compared outcomes in elderly (>65 years) versus younger participants in this trial.

Methods

Patients were randomized 2:1 to receive a once-per-cycle single subcutaneous injection of lipegfilgrastim 6 mg or placebo, with up to 4 cycles of every-3-week cisplatin (day 1) and etoposide (days 1–3). The primary end point was FN incidence during cycle 1. Outcomes were compared across treatment groups and by age groups (≤65 and >65 years).

Results

For patients aged ≤65 years, FN incidence during cycle 1 was similar in the lipegfilgrastim and placebo groups (3.0 vs 3.2 %, respectively), whereas for elderly patients, there was a reduction in FN incidence with lipegfilgrastim (0 vs 13.3 %, respectively). In both age subgroups, lipegfilgrastim showed a propensity to reduce the incidence and duration of severe neutropenia, time to absolute neutrophil count (ANC) recovery, and depth of ANC nadir. Adverse events were generally similar between groups.

Conclusions

This analysis suggests that in patients with a higher FN risk, such as the elderly patients of this study, lipegfilgrastim reduces not only the duration of severe neutropenia but also the incidence of FN.



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Transitions in the labor market after cancer: a comparison of self-employed workers and salaried staff

Abstract

Purpose

The aim of this study was to investigate whether the labor market mobility of a population of cancer survivors 2 years after diagnosis differed compared to the French general population by focusing on the differences between self-employed workers and salaried staff.

Methods

Coarsened exact matching was implemented to reduce the sampling bias introduced by the comparison of individuals from two different surveys. Then, labor market mobility was analyzed by estimating transition probability matrices from 2010 to 2012 under the framework of a continuous-time Markov technique and by estimating a two-step model.

Results

Salaried employees and self-employed workers from the general population were more likely to remain employed 2 years after 2010 compared to salaried employees and self-employed workers who survived cancer. There was no major difference between salaried and self-employed workers surviving cancer in terms of job retention.

Conclusions

French workers surviving cancer face the same difficulties that were observed in the National Cancer Survey of 2004: unemployment and inactivity caused by the diagnosis of cancer. Among cancer survivors, self-employed workers do not seem to be particularly more affected by inactivity than salaried staff. However, unemployment insurance is not compulsory for them, contrary to salaried staff. In this regard, self-employed workers might be a more vulnerable group.



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Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505)

Abstract

Purpose

Oxaliplatin and paclitaxel are commonly used chemotherapies associated with acute and chronic neuropathies. There is a need to better understand the similarities and differences of these clinical syndromes.

Methods

Neuropathy data were pooled from patients receiving adjuvant oxaliplatin and weekly paclitaxel or every 3 weeks of paclitaxel. Patients completed daily questionnaires after each chemotherapy dose and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy before each chemotherapy cycle and for 12 months post-treatment.

Results

Acute neuropathy symptoms from both drugs peaked around day 3. Acute symptoms experienced in cycle 1 predicted occurrence in subsequent cycles. Paclitaxel-induced acute symptoms were similar in intensity in each cycle and largely resolved between cycles. Oxaliplatin-induced acute symptoms were about half as severe in the first cycle as in later cycles and did not resolve completely between cycles. Both drugs caused a predominantly sensory chronic neuropathy (with numbness and tingling being more common than pain). Oxaliplatin-induced neuropathy worsened after the completion of treatment and began to improve 3 months post-treatment. In contrast, paclitaxel-induced neuropathy began improving immediately after chemotherapy cessation. During treatment, the incidence of paclitaxel sensory symptoms was similar in the hands and feet; with oxaliplatin, the hands were affected more than the feet. Both paclitaxel- and oxaliplatin-induced acute neurotoxicity appeared to predict the severity of chronic neuropathy, more prominently with oxaliplatin.

Conclusions

Knowledge of the similarities and differences between neuropathy syndromes may provide insight into their underlying pathophysiology and inform future research to identify preventative treatment approaches.



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Application of a standardized screening protocol for diagnosis of invasive mold infections in children with hematologic malignancies

Abstract

Purpose

This study describes a standardized screening protocol for diagnosis of invasive mold infections in pediatric oncology patients with neutropenia and prolonged or recurrent fever.

Methods

A retrospective chart review was performed of children receiving intensive chemotherapy for hematologic malignancies who developed invasive mold infections from 2004 to 2011. Characteristics and outcomes were compared before and after implementation of the screening protocol in November 2006. The screen includes direct nasal endoscopy performed at the bedside by an otorhinolaryngologist, noncontrast computed tomography (CT) of the chest, and abdominal ultrasound in patients with neutropenia and prolonged or recurrent fever.

Results

Fifty patients had proven, probable, or possible invasive mold infections. Before routine use of direct nasal endoscopy, invasive nasosinal disease was detected in 5 of 19 patients (26 %) and all had a compatible clinical presentation. Thirteen of 31 patients (42 %) in the post-screen group had nasosinal disease, and fever was the only sign for 8 patients (62 %). Twenty-four patients with nasosinal disease had a sinus CT, and radiologic findings of bony erosion or peri-sinus invasion were never detected. Eight of 19 patients in the pre-screen group died from mold infection (42.1 %) versus 4 of 31 (12.9 %) in the post-screen group (p = 0.04).

Conclusions

A screening protocol including direct nasal endoscopy, noncontrast chest CT, and abdominal ultrasound was effective in detecting invasive mold infections in at-risk patients. Nasosinal involvement often occurs before specific symptoms develop, and sinus CTs are insensitive and nonspecific. Bedside nasal endoscopy precludes radiation exposure associated with sinus CT and was associated with decrease in mold-related mortality, likely due to earlier diagnosis and initiation of appropriate antifungal therapy.



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Post-treatment problems of African American breast cancer survivors

Abstract

Purpose

African American breast cancer survivors (AABCS) have a lower survival rate across all disease stages (79 %) compared with White survivors (92 %) and often have more aggressive forms of breast cancer requiring multimodality treatment, so they could experience a larger burden of post-treatment quality of life (QOL) problems. This paper reports a comprehensive assessment of the number, severity, and domains of problems faced by AABCS within 5 years after treatment completion and identifies subgroups at risk for these problems.

Methods

A population-based random sample was obtained from the Pennsylvania Cancer Registry of African American females over 18 years of age who completed primary treatment for breast cancer in the past 5 years. A mailed survey was used to document survivorship problems.

Results

Two hundred ninety-seven AABCS completed the survey. The median number of survivor problems reported was 15. Exploratory factor analysis of the problem scale revealed four domains: emotional problems, physical problems, lack of resources, and sexuality problems. Across problem domains, younger age, more comorbid conditions, and greater medical mistrust were risk factors for more severe problems.

Conclusions

The results demonstrated that AABCS experienced significant problem burden in the early years after diagnosis and treatment. In addition to emotional and physical problem domains that were documented in previous research, two problem domains unique to AABCS included lack of resources and sexuality concerns. At risk groups should be targeted for intervention. The study results reported in this manuscript will inform future research to address problems of AABCS as they make the transition from cancer patient to cancer survivor.



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Prevalence of cancer chemotherapy-related problems, their relation to health-related quality of life and associated supportive care: a cross-sectional survey

Abstract

Purpose

The purpose of this study was to identify the treatment-associated problems that most impact on patients undergoing cancer chemotherapy, how problems relate to experiences of supportive care and variations in experience between cancer treatment centres.

Methods

A survey administered to patients at six cancer centres in England explored variations of prevalence of 17 cancer chemotherapy-associated problems and associated supportive care. Problem items were identified as the most frequently experienced and severe when experienced in a scoping and consensus exercise. A health-related quality of life (HRQoL) measure, the EQ5D, was included to measure impact of problems.

Results

A total of 363 completed questionnaires were returned (response rate 43 %, median 61 %). The most prevalent problem was 'tiredness/fatigued' (90 %), followed by 'changes in taste & smell' (69 %) and 'difficulty managing everyday tasks' (61 %). Significant variations in problem prevalence existed between centres, and some common problems were rarely reported in the literature. Regression analysis found that almost all problems were significantly associated with HRQoL, with social/emotional problems having as much impact on HRQoL as physical/psychological side effects of treatment. Greatest effect size was for difficulty managing everyday tasks. Respondents reported significant variations in supportive care between centres, with more supportive care received for physical/psychological problems than for social/emotional problems. Findings indicated that patients who received increased supportive care experienced less severe problems.

Conclusion

The most common and distressing chemotherapy-associated problems were identified. These problems are mitigated by quality supportive care. Routine measurement and monitoring of problem items and supportive care are warranted to facilitate benchmarking and service improvements both within and between cancer centres.



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Enhanced stimulation of anti-breast cancer T cells responses by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens

Developing safe and effective cancer vaccine formulations is a primary focus in the field of cancer immunotherapy. Dendritic cells (DC) are currently employed as cellular vaccine in clinical trials of tumor im...

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After 50 years: Future challenges in publishing cancer research



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Linc-ROR confers gemcitabine resistance to pancreatic cancer cells via inducing autophagy and modulating the miR-124/PTBP1/PKM2 axis

Abstract

Purpose

In this study, we investigated the regulation of linc-ROR on autophagy and gemcitabine resistance of pancreatic cancer cells and further studied the underlying involvement of the miR-124/PTBP1/PKM2 axis in this regulation.

Methods

Pancreatic cancer cell lines PANC-1 and MIAPaCa-2 cells were used as in vitro model. Autophagy was assessed by western blot of LC3 I/II and observation GFP-LC3 puncta. Cell viability was examined using CCK-8 assay. Cell apoptosis was examined by flow cytometric analysis of Annexin V/PI staining. QRT-PCR, RNA fluorescence in situ hybridization and dual luciferase assay were used to study the expression and the binding between linc-ROR and miR-124.

Results

Linc-ROR siRNA significantly sensitized PANC-1 and MIAPaCa-2 cells to gemcitabine, while linc-ROR overexpression significantly reduced the sensitivity. Linc-ROR knockdown reduced basal autophagy, while linc-ROR overexpression markedly increased basal autophagy in the cells. Linc-ROR siRNA showed similar effect as 3-MA on enhancing gemcitabine-induced cell apoptosis and also reduced PKM2 expression. MiR-124 overexpression restored PKM1 and reduced PKM2 levels in the cells. In addition, miR-124 mimics also alleviated autophagy in pancreatic cancer cells. Both miR-124 mimics and PKM2 siRNA enhanced gemcitabine-induced cell apoptosis. In both pancreatic cell lines and PADC tissues, linc-ROR is negatively correlated with miR-124 expression. In addition, dual luciferase assay verified two 8mer binding sites between miR-124 and linc-ROR.

Conclusion

Linc-ROR confers gemcitabine resistance to pancreatic cancer cells at least partly via inducing autophagy. There is a linc-ROR/miR-124/PTBP1/PKM2 axis involved in regulation of gemcitabine resistance in pancreatic cancer cells.



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After 50 years: Future challenges in publishing cancer research



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Validation of prostate-specific antigen laboratory values recorded in Surveillance, Epidemiology, and End Results registries

BACKGROUND

Researchers have used prostate-specific antigen (PSA) values collected by central cancer registries to evaluate tumors for potential aggressive clinical disease. An independent study collecting PSA values suggested a high error rate (18%) related to implied decimal points. To evaluate the error rate in the Surveillance, Epidemiology, and End Results (SEER) program, a comprehensive review of PSA values recorded across all SEER registries was performed.

METHODS

Consolidated PSA values for eligible prostate cancer cases in SEER registries were reviewed and compared with text documentation from abstracted records. Four types of classification errors were identified: implied decimal point errors, abstraction or coding implementation errors, nonsignificant errors, and changes related to "unknown" values.

RESULTS

A total of 50,277 prostate cancer cases diagnosed in 2012 were reviewed. Approximately 94.15% of cases did not have meaningful changes (85.85% correct, 5.58% with a nonsignificant change of <1 ng/mL, and 2.80% with no clinical change). Approximately 5.70% of cases had meaningful changes (1.93% due to implied decimal point errors, 1.54% due to abstract or coding errors, and 2.23% due to errors related to unknown categories). Only 419 of the original 50,277 cases (0.83%) resulted in a change in disease stage due to a corrected PSA value.

CONCLUSIONS

The implied decimal error rate was only 1.93% of all cases in the current validation study, with a meaningful error rate of 5.81%. The reasons for the lower error rate in SEER are likely due to ongoing and rigorous quality control and visual editing processes by the central registries. The SEER program currently is reviewing and correcting PSA values back to 2004 and will re-release these data in the public use research file. Cancer 2016. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.



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Validation of prostate-specific antigen laboratory values recorded in Surveillance, Epidemiology, and End Results registries

BACKGROUND

Researchers have used prostate-specific antigen (PSA) values collected by central cancer registries to evaluate tumors for potential aggressive clinical disease. An independent study collecting PSA values suggested a high error rate (18%) related to implied decimal points. To evaluate the error rate in the Surveillance, Epidemiology, and End Results (SEER) program, a comprehensive review of PSA values recorded across all SEER registries was performed.

METHODS

Consolidated PSA values for eligible prostate cancer cases in SEER registries were reviewed and compared with text documentation from abstracted records. Four types of classification errors were identified: implied decimal point errors, abstraction or coding implementation errors, nonsignificant errors, and changes related to "unknown" values.

RESULTS

A total of 50,277 prostate cancer cases diagnosed in 2012 were reviewed. Approximately 94.15% of cases did not have meaningful changes (85.85% correct, 5.58% with a nonsignificant change of <1 ng/mL, and 2.80% with no clinical change). Approximately 5.70% of cases had meaningful changes (1.93% due to implied decimal point errors, 1.54% due to abstract or coding errors, and 2.23% due to errors related to unknown categories). Only 419 of the original 50,277 cases (0.83%) resulted in a change in disease stage due to a corrected PSA value.

CONCLUSIONS

The implied decimal error rate was only 1.93% of all cases in the current validation study, with a meaningful error rate of 5.81%. The reasons for the lower error rate in SEER are likely due to ongoing and rigorous quality control and visual editing processes by the central registries. The SEER program currently is reviewing and correcting PSA values back to 2004 and will re-release these data in the public use research file. Cancer 2016. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.



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Dabrafenib in BRAFV600-mutated anaplastic pleomorphic xanthoastrocytoma

CNS Oncology Ahead of Print.


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Dabrafenib in BRAFV600-mutated anaplastic pleomorphic xanthoastrocytoma

CNS Oncology Ahead of Print.


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