Primary hyperparathyroidism revealed by a pathological fracture is very uncommon; in the majority of cases the discovery of lytic bone lesions on imaging examinations evokes in the clinician first a neoplastic...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 8 Δεκεμβρίου 2017
Unusual pathological fracture of the clavicle revealing primary hyperparathyroidism: a case report
PI3K in cancer: its structure, activation modes and role in shaping tumor microenvironment
Future Oncology, Ahead of Print.
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Can we predict the response to therapy in soft tissue sarcoma?
Future Oncology, Ahead of Print.
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Nonprogression with avelumab treatment associated with gains in quality of life in metastatic Merkel cell carcinoma
Future Oncology, Ahead of Print.
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PI3K in cancer: its structure, activation modes and role in shaping tumor microenvironment
Future Oncology, Ahead of Print.
http://ift.tt/2AIVQVd
Can we predict the response to therapy in soft tissue sarcoma?
Future Oncology, Ahead of Print.
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Therapy sequencing strategies in multiple myeloma: who, what and why?
Future Oncology, Ahead of Print.
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Osteoblast-like cells in human cancers: new cell type and reliable markers for bone metastasis
Future Oncology, Ahead of Print.
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Nonprogression with avelumab treatment associated with gains in quality of life in metastatic Merkel cell carcinoma
Future Oncology, Ahead of Print.
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Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors
Source:European Journal of Cancer, Volume 89
Author(s): Malaka Ameratunga, Maxime Chénard-Poirier, Irene Moreno Candilejo, Manuel Pedregal, Andrew Lui, David Dolling, Caterina Aversa, Alvaro Ingles Garces, Joo Ern Ang, Udai Banerji, Stan Kaye, Hui Gan, Bernard Doger, Victor Moreno, Johann de Bono, Juanita Lopez
BackgroundAlthough the neutrophil-lymphocyte ratio (NLR) is prognostic in many oncological settings, its significance in the immunotherapy era is unknown. Mechanistically, PD-1/PD-L1 inhibitors may alter NLR. We sought to characterise NLR kinetics in patients with advanced solid tumours treated with PD-1/PD-L1 inhibitors.MethodsElectronic records of patients treated with PD-1/PD-L1 inhibitors on phase I trials across three sites were reviewed. A high NLR (hNLR) was predefined as >5. Univariate logistic regression models were used for toxicity, response analyses and Cox models for overall survival (OS) and progression-free survival analyses. Landmark analyses were performed (cycle two, three). Longitudinal analysis of NLR was performed utilising a mixed effect regression model.ResultsThe median OS for patients with hNLR was 8.5 months and 19.4 for patients with low NLR, (hazard ratio [HR] = 1.85, 95% confidence interval [CI] 1.15–2.96, p = 0.01). On landmark analysis, hNLR was significantly associated with inferior OS at all time points with a similar magnitude of effect over time (p < 0.05). On multivariate analysis, NLR was associated with OS (HR 1.06, 95% CI 1.01–1.11, p = 0.01). NLR did not correlate with increased immune toxicity. Longitudinally, NLR correlated with response: NLR decreased by 0.09 (95% CI: −0.15 to −0.02; p = 0.01) per month in responders compared with non-responders.ConclusionshNLR at baseline and during treatment is adversely prognostic in patients with advanced malignancies receiving PD-1/PD-L1 blockade. Importantly, NLR reduced over time in responders to immunotherapy. Taken together, these data suggest that baseline and longitudinal NLR may have utility as a unique biomarker to aid clinical decision-making in patients receiving immunotherapy.
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The use of breast imaging for predicting response to neoadjuvant lapatinib, trastuzumab and their combination in HER2-positive breast cancer: Results from Neo-ALTTO
Source:European Journal of Cancer, Volume 89
Author(s): S. Di Cosimo, C. Campbell, H.A. Azim, G. Galli, G. Bregni, G. Curigliano, C. Criscitiello, M. Izquierdo, L. de la Pena, D. Fumagalli, L. Fein, J. Vinholes, W.M.J. Ng, M. Colleoni, A. Ferro, B.J. Naume, A. Patel, J. Huober, M.J. Piccart-Gebhart, J. Baselga, E. de Azambuja
AimTo determine the value of mammography and breast ultrasound (US) in predicting outcomes in HER2 positive breast cancer patients (pts) within Neo-ALTTO trial.Patients and methodsMammography and US were required at baseline, week 6 and surgery. Two independent blinded investigators reviewed the measurements and assigned the corresponding response category. Pts showing complete or partial response according to RECIST (v1.1) were classified as responders. The association between imaging response at week 6 or prior to surgery was evaluated with respect to pathological complete response (pCR) and event-free Survival (EFS).ResultsOf the 455 pts enrolled in the trial, 267 (61%) and 340 (77%) had evaluable mammography and US at week 6; 248 (56%) and 309 (70%) pts had evaluable mammography and US prior to surgery. At week 6, 32% and 43% of pts were classified as responders by mammography and US, respectively. pCR rates were twice as high for responders than non-responders (week 6: 46% versus 23% by US, p < 0.0001; 41% versus 24% by mammography, p = 0.007). Positive and negative predictive values of mammography and US prior to surgery were 37% and 35%, and 82% and 70%, respectively. No significant correlation was found between response by mammography and/or US at week 6/surgery and EFS.ConclusionsMammography and US were underused in Neo-ALTTO although US had the potential to assess early response whereas mammography to detect residual disease prior to surgery. Our data still emphasise the need for further imaging studies on pts treated with neoadjuvant HER2-targeted therapy.
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Comparing granulocyte colony–stimulating factor filgrastim and pegfilgrastim to its biosimilars in terms of efficacy and safety: A meta-analysis of randomised clinical trials in breast cancer patients
Source:European Journal of Cancer, Volume 89
Author(s): Edoardo Botteri, Andriy Krendyukov, Giuseppe Curigliano
BackgroundGranulocyte colony–stimulating factors (G-CSFs) are widely used to prevent neutropenia in cancer patients undergoing myelosuppressive chemotherapy. Several biosimilar medicines of G-CSF are now available, with their development involving a step-wise series of comparisons to demonstrate similarity to reference biologics. Randomised clinical trials (RCTs) are considered confirmatory, and for G-CSF biosimilars, patients with breast cancer (BC) undergoing myelosuppressive chemotherapy are the most sensitive population in which to confirm similarity. This meta-analysis aimed to compare the clinical efficacy and safety of approved or proposed G-CSF biosimilars (filgrastim or pegfilgrastim) with reference G-CSF in patients with BC.MethodsA Medline literature search up to March 2017 identified RCTs comparing biosimilar G-CSF to reference in BC patients. The primary efficacy end-point was mean difference in duration of severe neutropenia (DSN). Secondary efficacy end-points were differences in depth of absolute neutrophil count (ANC) nadir, time to ANC recovery and incidence of febrile neutropenia. Safety analyses included calculation of risk ratios for bone pain events, myalgia events and serious adverse events. Random effect models were fitted to obtain the pooled estimates of the mean difference for continuous outcomes and the risk ratio for dichotomous outcomes and their corresponding 95% confidence intervals (CIs).FindingsEight eligible RCTs were included in this meta-analysis. Overall difference in DSN between reference and biosimilar medicines was not statistically significant (0·06 d [95% CI −0·05, 0·17]). The analysis of secondary efficacy end-points showed no significant differences between reference biologics and biosimilar medicines, as well as the analysis of bone pain events, myalgia events and serious adverse events.
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Positron emission tomography/computed tomography evaluation of oncolytic virus therapy efficacy in melanoma
Source:European Journal of Cancer
Author(s): Viola Franke, Bernies van der Hiel, Bart A. van de Wiel, Willem M.C. Klop, Sylvia ter Meulen, Alexander C.J. van Akkooi
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NFS1 Expression Protects Lung Tumor Cells from Ferroptosis [Research Watch]
NFS1 activity is essential for maintenance of iron–sulfur cluster biosynthesis in response to oxidative stress.
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Mutant IDH1R132H Induces Transcriptional and Epigenomic Reprogramming [Research Watch]
A fraction of the chromatin state and DNA methylation changes induced by IDH1R132H are irreversible.
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Osteoblasts Promote Release of Tumor-Promoting SiglecFhi Neutrophils [Research Watch]
Lung tumors activate OCN+ osteoblasts in distant bone stroma to supply tumor-infiltrating neutrophils.
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Loss of DNA Repair Drives Neoantigen Renewal and Inhibits Tumor Growth [Research Watch]
DNA mismatch repair in tumors promotes enhanced immune surveillance.
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MYC Induces Immune Suppression to Promote Lung Tumorigenesis [Research Watch]
MYC promotes angiogenesis, inflammation, and immune suppression to accelerate KRASG12D tumor growth.
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Novel in vitro cancer models for optimizing anti-EGFR therapies
Pre-clinical models, that are able to recapitulate the biology and pathology of the original individual cancer, are needed to better investigate mechanisms of response and resistance to anticancer therapies. In this respect, novel in vitro models for metastatic colorectal cancer could be of high value.
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Dual Inhibition of PIK3C3 and FGFR as a New Therapeutic Approach to Treat Bladder Cancer
Purpose: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms. Experimental Design: Autophagy flux, morphology and intracellular organelles were evaluated by western blotting, transmission electron microscope and fluorescence microscope. Molecular docking, surface plasmon resonance assay were performed to identify drug-protein interaction. Lentiviral delivery of cDNA or shRNA, and CRISPR/Cas9-mediated genome editing were used to modulate gene expression. Mitochondrial oxygen consumption rate was measured by a Seahorse XFe24 extracellular flux analyzer, and ROS level was measured by flow cytometry. Results: MPT0L145 persistently increased incomplete autophagy and phase-lucent vacuoles at the peri-nuclear region, which were identified as enlarged and alkalinized late-endosomes. Screening of a panel of lipid kinases revealed that MPT0L145 strongly inhibits PIK3C3 with a KD value of 0.53 nmol/L. Ectopic expression of PIK3C3 reversed MPT0L145-increased cell death and incomplete autophagy. Four residues (Y670, F684, I760, D761) at the ATP-binding site of PIK3C3 are important for the binding of MPT0L145. Additionally, MPT0L145 promotes mitochondrial dysfunction, ROS production and DNA damage, which may in part, contribute to cell death. ATG5-knockout rescued MPT0L145-induced cell death, suggesting simultaneous induction of autophagy is crucial to its anticancer activity. Lastly, our data demonstrated that MPT0L145 is able to overcome cisplatin resistance in bladder cancer cells. Conclusions: MPT0L145 is a first-in-class PIK3C3/FGFR inhibitor, providing an innovative strategy to design new compounds that increase autophagy, but simultaneously perturb its process to promote bladder cancer cell death.
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Novel in vitro cancer models for optimizing anti-EGFR therapies
Pre-clinical models, that are able to recapitulate the biology and pathology of the original individual cancer, are needed to better investigate mechanisms of response and resistance to anticancer therapies. In this respect, novel in vitro models for metastatic colorectal cancer could be of high value.
http://ift.tt/2nKVSZO
Dual Inhibition of PIK3C3 and FGFR as a New Therapeutic Approach to Treat Bladder Cancer
Purpose: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms. Experimental Design: Autophagy flux, morphology and intracellular organelles were evaluated by western blotting, transmission electron microscope and fluorescence microscope. Molecular docking, surface plasmon resonance assay were performed to identify drug-protein interaction. Lentiviral delivery of cDNA or shRNA, and CRISPR/Cas9-mediated genome editing were used to modulate gene expression. Mitochondrial oxygen consumption rate was measured by a Seahorse XFe24 extracellular flux analyzer, and ROS level was measured by flow cytometry. Results: MPT0L145 persistently increased incomplete autophagy and phase-lucent vacuoles at the peri-nuclear region, which were identified as enlarged and alkalinized late-endosomes. Screening of a panel of lipid kinases revealed that MPT0L145 strongly inhibits PIK3C3 with a KD value of 0.53 nmol/L. Ectopic expression of PIK3C3 reversed MPT0L145-increased cell death and incomplete autophagy. Four residues (Y670, F684, I760, D761) at the ATP-binding site of PIK3C3 are important for the binding of MPT0L145. Additionally, MPT0L145 promotes mitochondrial dysfunction, ROS production and DNA damage, which may in part, contribute to cell death. ATG5-knockout rescued MPT0L145-induced cell death, suggesting simultaneous induction of autophagy is crucial to its anticancer activity. Lastly, our data demonstrated that MPT0L145 is able to overcome cisplatin resistance in bladder cancer cells. Conclusions: MPT0L145 is a first-in-class PIK3C3/FGFR inhibitor, providing an innovative strategy to design new compounds that increase autophagy, but simultaneously perturb its process to promote bladder cancer cell death.
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NKG2D-based CAR-T cells and radiotherapy exert synergistic efficacy in glioblastoma
Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models. ChNKG2D T cells demonstrated high IFN-γ production and cytolytic activity in vitro. Upon systemic administration in vivo, chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse events, prolonged survival, and cured a fraction of glioma-bearing mice. Surviving mice were protected long-term against tumor re-challenge. Mechanistically, this was not solely the result of a classical immune memory response, but rather involved local persistence of chNKG2D T cells. A subtherapeutic dose of local radiotherapy in combination with chNKG2D T cell treatment resulted in synergistic activity in 2 independent syngeneic mouse glioma models by promoting migration of CAR T cells to the tumor site and increased effector functions. We thus provide preclinical proof-of-concept of NKG2D CAR T cell activity in mouse glioma models and demonstrate efficacy, long-term persistence, and synergistic activity in combination with radiotherapy, providing a rationale to translate this immunotherapeutic strategy to human glioma patients.
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NKG2D-based CAR-T cells and radiotherapy exert synergistic efficacy in glioblastoma
Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models. ChNKG2D T cells demonstrated high IFN-γ production and cytolytic activity in vitro. Upon systemic administration in vivo, chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse events, prolonged survival, and cured a fraction of glioma-bearing mice. Surviving mice were protected long-term against tumor re-challenge. Mechanistically, this was not solely the result of a classical immune memory response, but rather involved local persistence of chNKG2D T cells. A subtherapeutic dose of local radiotherapy in combination with chNKG2D T cell treatment resulted in synergistic activity in 2 independent syngeneic mouse glioma models by promoting migration of CAR T cells to the tumor site and increased effector functions. We thus provide preclinical proof-of-concept of NKG2D CAR T cell activity in mouse glioma models and demonstrate efficacy, long-term persistence, and synergistic activity in combination with radiotherapy, providing a rationale to translate this immunotherapeutic strategy to human glioma patients.
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Pioglitazone Inhibits Periprostatic White Adipose Tissue Inflammation in Obese Mice
Obesity is associated with an increased incidence of high-grade prostate cancer (PC) and poor prognosis for PC patients. Recently, we showed that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by crown-like structures (CLS) consisting of dead or dying adipocytes surrounded by macrophages, was associated with high-grade PC. It's possible, therefore, that agents that suppress periprostatic WAT inflammation will alter the development or progression of PC. Pioglitazone, a ligand of PPAR is used to treat diabetes and possesses anti-inflammatory properties. Here our main objectives were to determine if pioglitazone inhibited obesity-related periprostatic WAT inflammation in mice and then to elucidate the underlying mechanism. Treatment with pioglitazone reduced the density of CLS in periprostatic fat, and suppressed levels of TNF-alpha, TGF-beta and the chemokine monocyte chemoattractant protein-1 (MCP-1). Importantly, the ability of pioglitazone to suppress periprostatic WAT inflammation was abrogated in MCP-1 knock out mice. Pioglitazone caused dose-dependent induction of both adiponectin, an anti-inflammatory adipokine, and its receptor AdipoR2 in cultured 3T3-L1 cells and in periprostatic WAT of obese mice. Pioglitazone blocked TNF-α-mediated induction of MCP-1 in 3T3-L1 cells, an effect that was attenuated when either adiponectin or AdipoR2 were silenced. Taken together, pioglitazone-mediated induction of adiponectin suppressed the elevation in MCP-1 levels thereby attenuating obesity-related periprostatic WAT inflammation. These findings strengthen the rationale for future efforts to determine whether targeting the PPAR-adiponectin-MCP-1 axis will decrease periprostatic adipose inflammation and thereby reduce the risk of high-grade PC or improve outcomes for men with PC.
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Adiposity, Inflammation and Breast Cancer Pathogenesis in Asian Women
Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus western countries. Breast WAT and fasting blood were prospectively collected from Taiwanese women undergoing mastectomy for breast cancer treatment. Body composition was measured in a subgroup using bioelectrical impedance analysis. WAT inflammation was defined by the presence of crown-like structures of the breast which are composed of dead or dying adipocytes surrounded by macrophages. Findings were compared with US Caucasian women. In the Taiwanese cohort (n=72), breast WAT inflammation was present in 31 (43%) women and was associated with elevated BMI (P<0.01) and increased levels of body fat (P<0.01), C-reactive protein (P=0.02), triglycerides (P<0.01), insulin resistance scores (P=0.04), and lower HDL cholesterol (P<0.01). ER+ tumors were associated with greater body fat versus other subtypes (P=0.03). Compared with US Caucasians (n=267), Taiwanese women had larger breast adipocytes despite lower BMI after adjusting for BMI and menopausal status (P=0.01). A subclinical inflammatory state associated with increased adiposity and metabolic dysfunction could contribute to breast cancer pathogenesis in Asian women.
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A Hat-Trick Knock-Reversible Triple Organ Injury in a New Mother With HELLP Syndrome
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Sodium Bicarbonate for Control of ICP: A Systematic Review
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Intraoperative Blood Pressure Discrepancy Between Arms During Prone Position!
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Perioperative and Anesthetic Considerations for Neurosurgical Laser Interstitial Thermal Therapy Ablations
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Innovations in Functional Neurosurgery and Anesthetic Implications
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Complementary Use of Effect Site-Target Controlled Infusion and SmartPilot View for Anesthetic Management in Semi-awake Craniotomy Near BIS 85
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Ultra–low-dose Naloxone as an Adjuvant to Patient Controlled Analgesia (PCA) With Morphine for Postoperative Pain Relief Following Lumber Discectomy: A Double-blind, Randomized, Placebo-controlled Trial
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Propofol Pharmacodynamics and Bispectral Index During Key Moments of Awake Craniotomy
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Posterior Reversible Encephalopathy Syndrome Triggered by Vertebral Artery Angiogram
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The Correlation Between Recordable MEPs and Motor Function During Spinal Surgery for Resection of Thoracic Spinal Cord Tumor
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Airway Management With a Stereotactic Headframe In Situ—A Mannequin Study
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Cortical Arousal With Deep Brain Stimulation After General Anesthesia for Laparoscopic Cholecystectomy
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Hemodynamic Disturbances in the Early Phase After Subarachnoid Hemorrhage: Regional Cerebral Blood Flow Studied by Bedside Xenon-enhanced CT
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Analgosedation With Dexmedetomidine in a Patient With Superior Vena Cava Syndrome in Neurosurgery
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Neonatal Sevoflurane Exposure Induces Adulthood Fear-induced Learning Disability and Decreases Glutamatergic Neurons in the Basolateral Amygdala
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Intravenous Clevidipine for Inducing Hypotensive Challenge During Carotid Balloon Test Occlusion
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The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits
Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.
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Patient reported dry mouth: Instrument comparison and model performance for correlation with quality of life in head and neck cancer survivors
To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN).
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Tai Chi and Qigong for cancer-related symptoms and quality of life: a systematic review and meta-analysis
Abstract
Purpose
This study aims to summarize and critically evaluate the effects of Tai Chi and Qigong (TCQ) mind–body exercises on symptoms and quality of life (QOL) in cancer survivors.
Methods
A systematic search in four electronic databases targeted randomized and non-randomized clinical studies evaluating TCQ for fatigue, sleep difficulty, depression, pain, and QOL in cancer patients, published through August 2016. Meta-analysis was used to estimate effect sizes (ES, Hedges' g) and publication bias for randomized controlled trials (RCTs). Methodological bias in RCTs was assessed.
Results
Our search identified 22 studies, including 15 RCTs that evaluated 1283 participants in total, 75% women. RCTs evaluated breast (n = 7), prostate (n = 2), lymphoma (n = 1), lung (n = 1), or combined (n = 4) cancers. RCT comparison groups included active intervention (n = 7), usual care (n = 5), or both (n = 3). Duration of TCQ training ranged from 3 to 12 weeks. Methodological bias was low in 12 studies and high in 3 studies. TCQ was associated with significant improvement in fatigue (ES = − 0.53, p < 0.001), sleep difficulty (ES = − 0.49, p = 0.018), depression (ES = − 0.27, p = 0.001), and overall QOL (ES = 0.33, p = 0.004); a statistically non-significant trend was observed for pain (ES = − 0.38, p = 0.136). Random effects models were used for meta-analysis based on Q test and I 2 criteria. Funnel plots suggest some degree of publication bias. Findings in non-randomized studies largely paralleled meta-analysis results.
Conclusions
Larger and methodologically sound trials with longer follow-up periods and appropriate comparison groups are needed before definitive conclusions can be drawn, and cancer- and symptom-specific recommendations can be made.
Implications for Cancer Survivors
TCQ shows promise in addressing cancer-related symptoms and QOL in cancer survivors.
http://ift.tt/2BWPxNU
Healthcare system barriers to long-term follow-up for adult survivors of childhood cancer in British Columbia, Canada: a qualitative study
Abstract
Purpose
Risk-stratified life-long follow-up care is recommended for adult childhood cancer survivors (CCS) to ensure appropriate prevention, screening, and management of late effects. The identification of barriers to long-term follow-up (LTFU), particularly in varying healthcare service contexts, is essential to develop and refine services that are responsive to survivor needs. We aimed to explore CCS and healthcare professionals (HCP) perspectives of healthcare system factors that function as barriers to LTFU in British Columbia, Canada.
Methods
We analyzed data from 43 in-depth interviews, 30 with CCS and 13 with HCP, using qualitative thematic analysis and constant comparative methods.
Results
Barriers to accessible, comprehensive, quality LTFU were associated with the following: (1) the difficult and abrupt transition from pediatric to adult health services, (2) inconvenient and under-resourced health services, (3) shifting patient-HCP relationships, (4) family doctor inadequate experience with late effects management, and (5) overdue and insufficient late effects communication with CCS.
Conclusions
Structural, informational, and interpersonal/relational healthcare system factors often prevent CCS from initially accessing LTFU after discharge from pediatric oncology programs as well as adversely affecting engagement in ongoing screening, surveillance, and management of late effects.
Implications for Cancer Survivors
Understanding the issues faced by adult CCS will provide insight necessary to developing patient-centered healthcare solutions that are key to accessible, acceptable, appropriate, and effective healthcare.
http://ift.tt/2BOt4C2
Evaluation of renal function change during first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma
Abstract
Background
The change in renal function induced by first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma remains unclear. Methods
One hundred and thirty-four patients were evaluated. Sunitinib (SU) and sorafenib (SO) were administered to 91 (67.9%) and 43 (32.1%) patients, respectively. The change in estimated glomerular filtration rate (ΔeGFR) was calculated as [(eGFR at each time point – pre-treatment eGFR)/pre-treatment eGFR] × 100. ΔeGFR was compared between SU- and SO users using a mixed-effects model for repeated measures data with two or greater. Additionally, predictors for ΔeGFR ≤ −10% at 6 months after therapy initiation were evaluated using multivariate logistic regression analysis. Results
Throughout the 24 months after therapy initiation, ΔeGFR was negatively greater in SU users, compared with that in SO users (P < 0.0001). In SU users, renal dysfunction was observed regardless of pre-treatment chronic kidney disease (CKD) status, whereas the magnitude of renal dysfunction was milder in SO users. In SO users without pre-treatment CKD, renal function did not significantly deteriorate. Moreover, ΔeGFR ≤ −10% was more frequently observed in SU users after 3 months (P = 0.0121) and 6 months (P = 0.0009). Finally, SU usage was an independent predictor for ΔeGFR ≤ −10% at 6 months (odds ratio 8.87, P = 0.0053), along with pre-treatment hypertension (odds ratio 4.69, P = 00072). Conclusions
Deterioration of renal function was stronger with SU than SO. During SU therapy, renal function should be monitored and pre-treatment kidney function should be taken into consideration for therapy selection.http://ift.tt/2jxFCXH
Facial flushing after alcohol intake as a predictor for a high risk of synchronous or metachronous cancer of the upper gastrointestinal tract
Abstract
Background
In Japan, there has been a lot of reports showing an association between facial flushing after light alcohol consumption and heterozygosity for inactive aldehyde dehydrogenase-2 (ALDH2). Persons with inactive ALDH2 may have a higher risk of alcohol-related oral, pharyngeal and esophageal cancers, compared with those with wild-type ALDH2. The purpose of this study was to examine whether flushers with oral or pharyngeal squamous cell carcinoma have an increased risk of synchronous or metachronous cancer of the upper gastrointestinal (UGI) tract. Methods
A retrospective study was performed by medical chart review and through a questionnaire sent to 285 patients treated for oral and pharyngeal cancer. Responses were obtained from 150 patients (52.6%), who were classified as flushers or non-flushers, smokers (≥20 pack-year; 1 pack-years = number of cigarettes/20 per day) or non-smokers, and drinkers (≥14 units of alcohol consumption per week; 1 unit = 22 g) or non-drinkers. Relationships of these factors with occurrence of second primary cancers (SPCs) in the UGI tract were investigated. Results
In Kaplan–Meier analysis, there was a significantly higher rate of SPC at 5 years in flushers and drinkers, but no relationship with smoking. In multivariate analyses, a history of flushing was significantly associated with SPC in the UGI tract (HR 2.64, 95% CI 1.25–5.52, P = 0.0109), but not with smoking or alcohol consumption. Conclusions
A simple interview on history of facial flushing after alcohol intake can be useful for identifying patients at high risk for synchronous or metachronous cancers of the UGI tract.http://ift.tt/2B2ChtC
Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer
Abstract
The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection.http://ift.tt/2jvsL8k
Active heavy cigarette smoking is associated with poor survival in Japanese patients with advanced renal cell carcinoma: sub-analysis of the multi-institutional national database of the Japanese Urological Association
Abstract
Objective
The association between cigarette smoking and survival in patients with renal cell carcinoma is not well studied. We examined the impact of cigarette smoking on survival of patients with advanced renal cell carcinoma using the multi-institutional national database of the Japanese Urological Association. Methods
From 340 Japanese institutions, 963 patients with renal cell carcinoma of clinical Stage 3 or higher were analyzed. Univariate analysis using the Kaplan–Meier method and multivariate Cox regression models with stepwise selection was used to evaluate overall and cause-specific survival. Results
Median duration of follow-up was 842 days, and overall and cancer death occurred in 392 (40.7%) and 351 (36.4%) patients, respectively. In multivariate analysis, smoking 20 or more cigarettes daily at diagnosis was associated with poorer overall and cancer-specific survival, especially in Stage 3. According to a Cox proportional hazards model, heavy cigarette smoking at diagnosis and the variables of underweight, fever symptoms, serum lactic dehydrogenase value, serum C-reactive protein value, serum creatinine value, Eastern Cooperative Oncology Group performance status, nephrectomy and clinical stage were significant (P < 0.05) for overall and cancer-specific survival. Conclusions
We could compare the smoking status at diagnosis and the prognosis of renal cell carcinoma at national wide scale. Heavy active smoking was an independent prognostic factor for overall and cancer-specific survival in patients with advanced renal cell carcinoma, especially in Stage 3.http://ift.tt/2B4P1zO
Supportive care needs and psychological distress and/or quality of life in ambulatory advanced colorectal cancer patients receiving chemotherapy: a cross-sectional study
Abstract
Background
Although currently many advanced colorectal cancer patients continuously receive chemotherapy, there are very few findings with regard to the supportive care needs of such patients. Methods
The purposes of this study were to investigate the patients' perceived needs and the association with psychological distress and/or quality of life, and to clarify the characteristics of patients with a high degree of unmet needs. Ambulatory colorectal cancer patients who were receiving chemotherapy were asked to complete the Short-Form Supportive Care Needs Survey questionnaire, which covers five domains of need (health system and information, psychological, physical, care and support, and sexuality needs), the Hospital Anxiety and Depression Scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Results
Complete data were available for 100 patients. Almost all of the top 10 most common unmet needs belonged to the psychological domain. The patients' total needs were significantly associated with both psychological distress (r = 0.65, P < 0.001) and quality of life (r = −0.38, P < 0.001). A multiple regression analysis revealed that the female gender was significantly associated with higher total needs. Conclusions
The moderate to strong associations that exist between patients' needs and psychological distress and/or quality of life suggest that interventions that respond to patients' needs may be one possible strategy for ameliorating psychological distress and enhancing quality of life. Female patients' needs should be evaluated more carefully.http://ift.tt/2jy5BOD
JLCS medical practice guidelines for thymic tumors: summary of recommendations
Abstract
The Guideline Committee of the Japan Lung Cancer Society (JLCS) for Thymic Tumors published the Medical Practice Guideline for Thymic Tumors in Japanese as Chapter 3 of the Medical Practice Guidelines for Lung Cancers according to evidence-based medicine in December 2016. This medical practice guideline is the first for thymic epithelial tumors in Japan, and comprises a set of recommendations covering clinical diagnosis, treatment and pathological diagnosis. Thymic epithelial tumors include thymoma, thymic carcinoma and thymic neuroendocrine tumor. The recommendations for clinical diagnosis concern detection of the symptoms, blood and serum tests according to clinical presentation, essential imaging for differential diagnosis and staging, and the necessity and methods of definitive diagnosis. The recommendations for treatment are dependent on tumor stage and recurrence status, and the treatment modalities included surgery, radiation therapy, chemotherapy and multimodality therapy. Those for pathological diagnosis deal with the handing methods of resected specimen and essential reporting contents for pathological diagnosis. Since data from large-scale analyses or clinical studies of thymic epithelial tumor are limited due to its low prevalence, the relevant recommendations and grading were based on available reported evidence and expert opinions as well as diagnostic methods and treatments commonly used in Japan. This report summarizes the recommendations concerning each topic addressed by this JLCS guideline for thymic tumors.http://ift.tt/2B4OU7m
Invasive micropapillary carcinoma component is an independent prognosticator of poorer survival in Stage III colorectal cancer patients
Abstract
Background
Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCs per se Methods
We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment. We compared the clinicopathological characteristics and survival outcomes of colorectal cancer patients with IMPCs to those without. Results
Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of 18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101 patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease-free survival (DFS) rates were significantly worse for Stage III patients with IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in patients with other stages. Multivariate analyses of patients with Stage III colorectal cancer found IMPC to be associated with significantly worse DFS (P = 0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only significantly associated with tumor invasion (P = 0.045) and venous invasion (P = 0.045) in Stage III tumors. Conclusions
Identifying IMPC components in Stage III colorectal cancer is crucial, as their presence is significantly associated with poorer survival.http://ift.tt/2jy5ClF
Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma
Abstract
Purpose
We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. Material and methods
Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. Results
In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. Conclusion
Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.http://ift.tt/2AZFIRZ
Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study
Abstract
Introduction
We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. Methods
This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Results
Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). Conclusion
The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period.http://ift.tt/2y8AQo4
Loss of CD15 expression in clear cell renal cell carcinoma is correlated with worse prognosis in Chinese patients
Abstract
Purpose
To explore the role of CD15 expression in the prognosis of clear cell renal cell carcinoma (ccRCC) in Chinese patients. Methods
The study included 301 patients who had undergone surgery for localized ccRCC. All paraffin-embedded tumor sections were collected to make a set of tissue microarrays. CD15 expression was assessed by immunohistochemistry. The relationship between CD15 expression and survival parameters, clinicopathology features was assessed. Kaplan–Meier and Cox proportional hazards model were utilized to determine the correlation between CD15 expression and overall survival (OS). Results
The median follow-up time was 54.6 months (range, 3–121 months). The positive rate of CD15 expression was 81.7% (246/301). The cut-off value of CD15 expression was defined as the maximum for Youden index by plotting the receiver operating characteristic curve for survival status. As the threshold was 0.5, all cases were divided into two groups: positive expression group and negative expression group. In correlation analysis, loss of CD15 expression was correlated with female gender, higher Fuhrman nuclear grade, with sarcomatoid differentiation, with necrosis, and with vascular invasion. Kaplan–Meier analysis indicated that the OS time of patients with loss of CD15 expression was shorter than that of patients with positive CD15 expression (P = 0.013). Conclusion
CD15 is a significant prognostic factor in clear cell renal cell carcinoma.http://ift.tt/2yPAeqP
Cardiac paraganglioma with a novel germline mutation of succinate dehydrogenase gene D
Abstract
A 58-year-old woman with a past medical history of a carotid body tumor, resected 4 months prior to presentation, was admitted to our hospital for treatment of a cardiac tumor that was identified on post-operative echocardiography and chest computed tomography. The cardiac tumor was surgically removed and identified pathologically as a paraganglioma, similarly to the carotid body tumor. Genetic analysis of both tumors identified a non-synonymous mutation in the succinate dehydrogenase (SDH) gene D, Exon4, c.320T>C, p.Leu107Pro showing co-segregation with paternal transmission and maternal imprinting among family members. This novel mutation appears to be the cause of familial paraganglioma in this patient.http://ift.tt/2y8VFzP
Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene
Abstract
Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors.http://ift.tt/2yPzxxM
Baseline risk stratification or duration of prior therapy predicts prognosis in patients with metastatic renal cell carcinoma treated with axitinib
Abstract
Background
To elucidate the clinical prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with axitinib. Methods
A total of 58 patients were retrospectively analyzed. All patients received axitinib treatment for mRCC at Keio University hospital in Japan. Baseline clinical factors and on treatment adverse events were assessed to predict survival. Results
The median progression free survival (PFS) for axitinib treatment was 10.9 months (95% CI 5.8–13.5), and the median overall survival (OS) from the start of axitinib treatment was 39.8 months (95% CI 25.9–NR), respectively. The PFS (P < 0.0001) and OS (P = 0.0022) were significantly correlated with the International mRCC Database Consortium (IMDC) classification, respectively. The PFS and OS were significantly longer in patients who received longer prior treatment (P = 0.0424 and 0.0067, respectively). On-treatment hypertension, hand foot syndrome and hypothyroidism were associated with longer PFS (P = 0.0002, 0.0055 and 0.0290, respectively). On-treatment hypertension, diarrhea, and hand foot syndrome were associated with longer OS (P = 0.0004, 0.0036 and 0.0115, respectively). Conclusions
Baseline and on treatment factors are identified as prognostic markers in mRCC patients treated with axitinib. Our findings might be helpful for clinicians to select the best treatment to individual patients.http://ift.tt/2y8S6JF
Switch to miriplatin for multinodular hepatocellular carcinoma unresponsive to transarterial chemoembolization with epirubicin: a prospective study
Abstract
Objective
The aim of this prospective study was to evaluate the efficacy of transarterial chemoembolization using miriplatin, a platinum-based anticancer drug, as a retreatment regimen for hepatocellular carcinoma (HCC) unresponsive to chemoembolization using epirubicin. Methods
Between April 2013 and December 2014, we enrolled 57 consecutive chamoembolization-naïve patients with unresectable HCC, and performed chemoembolization with epirubicin. Treatment effect, necrotizing rate of the target nodules, was evaluated at 1–3 months after treatment using contrast-enhanced CT or MRI. We subsequently included retreatment chemoembolization with miriplatin for patients whose treatment effect was <50% after chemoembolization with epirubicin. The treatment effect after chemoembolization with miriplatin and the liver function before and after chemoembolization were evaluated. Results
Eighteen patients of the 57 showed a treatment effect <50% after chemoembolization with epirubicin, and were switched to chemoembolization with miriplatin. The treatment effect after chemoembolization with miriplatin was ≥50% in four (22%) patients. Four of the remaining 14 (78%) patients who had <50% necrosis exhibited deterioration of the liver function after chemoembolization with miriplatin. Univariate analysis indicated that an alpha-fetprotein-L3 level <10% and a serum albumin level ≥3.6 g/dl were predictive factors of therapeutic response after chemoembolization with miriplatin (P < 0.05). However, there was no predictive factor regarding the deterioration of liver function after chemoembolization with miriplatin. Conclusions
In unresectable HCC patients who were unresponsive to chemoembolization with epirubicin, switching the chemotherapeutic regimen to a platinum-based anticancer drug in retreatment chemoembolization should be considered as a treatment option. Trial registration: UMIN 000015887http://ift.tt/2yPzkuu
Error in Figure and Methods Section
In the article by Esserman et al titled "Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades," there are errors in Figure 1 and in the Methods section. The boxes at the bottom of Figure 1 (CONSORT diagram) should read from left to right: "313 Received no endocrine treatment" and "339 Received tamoxifen treatment." The last line of the second paragraph of the Methods section should read "RNA was extracted, and 652 patients had 70-gene signature classification passing the quality check (Figure 1): 339 had received tamoxifen, and 313 had not received adjuvant systemic therapy." The article has been corrected online.
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Abiraterone for Metastatic Prostate Cancer With Suboptimal Response to Hormone Induction
This study evaluated the use of abiraterone acetate plus prednisone in men with metastatic prostate cancer.
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Cytotoxic Tumor-Infiltrating Lymphocytes in Metastatic HER2-Positive Breast Cancer
This secondary analysis of a phase 3 randomized clinical trial investigates the role of tumor-infiltrating lymphocytes in predicting outcomes in patients with HER2-positive metastatic breast cancer randomized to antibody vs small molecule–based anti-HER2 therapy.
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End-of-Life Care and Costs for Older Patients With Malignant Brain Tumors
This study analyzes Medicare claims data associated with end-of-life hospitalization care and costs for elderly patients with a malignant brain tumor.
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Is “Do Everything!” Always Appropriate?
To the Editor I read with interest the Viewpoint by Beer and Prasad. I agree with the points they raised regarding the book by DeVita and DeVita-Raeburn, The Death of Cancer. Their book is a good historical perspective of the development of modern multidrug chemotherapy and has a fascinating account of DeVita's team's success in achieving high rates of complete remissions and even cures in advanced Hodgkin disease and other hematological malignant neoplasms. However, that approach has had limited success in the treatment of most other cancers. The attitude of "never give up" causes more harm than good. Unregulated, unsupervised clinical trials have caused severe harm to many patients, as illustrated by the Jesse Gelsinger case.
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Palliative Care for All
This Viewpoint examines possible unintended harms of the new American Society of Clinical Oncology guidelines that state that all patients with advanced cancer receive palliative care from interdisciplinary specialty palliative care teams.
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To ProtecT Our Patients With Prostate Cancer
This Viewpoint examines the conclusions of the ProtecT randomized clinical trial and argues that, instead of radical therapy, appropriate patients for active surveillance should be chosen and active surveillance strategies optimized to avoid the small increased risk of distant metastasis seen in ProtecT.
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Mutation Frequencies in Patients With Early-Onset Colorectal Cancer
To the Editor The article by Pearlman et al broaches a matter of high importance; 1 in 6 patients with a diagnosis of early-onset colorectal cancer (CRC) carries a germline defect in a known cancer susceptibility gene. Of these, 1 in 8 carries a CRC-predisposing allele while 3% of the individuals tested carried mutations in breast cancer genes with high or moderate penetrance. These might be simply incidental findings and although they can be clinically actionable for the individuals themselves and their families, a direct association with CRC predisposition has not been established.
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Will Machine Learning Tip the Balance in Breast Cancer Screening?
This Viewpoint examines the potential use of machine learning to improve imaging-based breast cancer screening performance and associated patient outcomes.
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Small Cell, Large Impact
Recurrence after recurrence after recurrence.First the nodes, then the bones, then the lungs.The liver was just a pit stop along the wayfrom your cervix to your brain."Guess who?" says the tumor,flamboyantly small and blue and round as it is.We've captured it and stained it,cut it out, shot beams at it,bathed it in potent chemicals,studied it in every which way.
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The Trade-off Between Speed and Safety in Drug Approvals
This Viewpoint discusses the need to balance speed of approval and safety of drugs in the US Food and Drug Administration's process of drug approval.
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The Genetic Landscape of Small Cell Carcinoma of the Urinary Bladder
This review investigates recent advances in the understanding of the genetics of small cell carcinoma of the urinary bladder and the potential implications in diagnosis, prognosis, and treatment.
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Biosimilars
This Viewpoint discusses why the market for biosimilars and the cost savings related to their use have remained smaller than expected in the United States and suggests ways to rectify this situation.
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Mutation Frequencies in Patients With Early-Onset Colorectal Cancer
To the Editor Pearlman et al reported that in screening patients with colorectal cancer (CRC) for inherited germline mutated genes predisposing to CRC, 13 of 72 (18%) "had mutations in genes not traditionally associated with CRC risk."(p464) They note that "all patients found to have pathogenic mutations received genetic counseling and current evidence-based guidelines for intensive cancer surveillance based on their mutation status."(p469) However, these guidelines are not based on any known relevance of incidentally discovered germline mutations.
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Afraid That I’ll Not Be Afraid—A Paradox of Care
Mark, a 49-year-old nonsmoker, was diagnosed 2 years ago with metastatic adenocarcinoma of the lung. When he was given the diagnosis, he fell into despair, his mind befogged, no future, in total darkness, total solitude. He wanted to be left alone but was also afraid that his friends and loved ones would abandon him. He cried; he cried a great deal. He became depressed; he began saying good-bye to friends because he was convinced he had only a few months to live. He withdrew into himself and stopped wanting to see anyone. He also became aggressive toward his wife and children. He was beginning a process of separation from the world, from life. This was how he was when he came to my clinic accompanied by his wife. He was suffering from dyspnea, pain, and a deep feeling of desperation. He had chosen not to speak, letting his wife explain what he was suffering from. He averted his eyes, staring into space as if he were not there or just passing through by chance. It was if his wife and I were not talking about him, sharing his story. Initially, I let his wife speak but then began to ask him questions directly. But his wife answered promptly, always stepping in for him.
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Mutation Frequencies in Patients With Early-Onset Colorectal Cancer—Reply
In Reply We appreciate the opportunity to respond to the letters received regarding our article. We have made every effort to thoroughly address the raised questions and comments.
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Mother Tongue
"It is a part of who we are. You will appreciate it later," my mother repeatedly told me as a child the many times I refused to respond to her in Hindi. Although I was born in the United States, I always felt slightly foreign. For one thing, my name, Charu Agrawal, sounds foreign. My mother would pack foods like aloo gobi and parathas in my lunch box. I constantly found myself trying to fit in with my classmates, who spoke English at home, had American-sounding names like Brittany, and brought turkey sandwiches for lunch. However, as immigrants to this country, my parents were determined to assimilate into American culture while retaining their Indian identity. Speaking Hindi was central to their identity. In contrast, I was desperately trying to fit in, so speaking English, sometimes with a Texas twang, was mandatory among my schoolmates. Nonetheless, I soon learned that I had better speak Hindi in our household if I expected any consideration from my parents, such as permission to attend birthday parties and sleepovers, and later, to borrow the family car. So, I spoke Hindi purely as a survival tactic, not as a nod to my cultural heritage. While I spent the majority of my childhood thinking that Hindi would not have any practical use outside our home, my perspective changed one day on hospital rounds.
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Treatment Beyond Progression With Immune Checkpoint Inhibitors
The development and subsequent approval of antibodies against the immune regulators programmed cell death receptor 1 (PD-1) and its ligand PD-L1 is changing treatment paradigms in a variety of cancers, with 5 of these antibodies approved to date. Whereas immune checkpoint inhibitor development is among the most successful and heavily investigated areas in oncology drug development, several uncertainties remain regarding how best to use these therapies in clinical practice. Important questions include how best to predict, identify, and optimally manage immune-related adverse events, the utility of complementary or companion diagnostic tests to predict which patients will and will not benefit, optimal dosing and scheduling, and the optimal duration of treatment.
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JAMA Oncology
JAMA Oncology is committed to publishing influential original research, opinions, and reviews that advance the science of oncology and improve the clinical care of patients with cancer.
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Patterns of Treatment Failure and Postrecurrence Outcomes in Head and Neck Cancer
This cohort study assesses patterns of treatment failure and postrecurrence outcomes among patients with head and neck squamous cell carcinoma after chemoradiotherapy using contemporary radiotherapy techniques.
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Human Microbiomes Influence Cancer Therapy
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Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results
Abstract
Background
Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). The optimal chemotherapy regimen is unclear. Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact. We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response. Methods
Patients with TNBC (estrogen receptor/progesterone receptor < 1%, human epidermal growth factor receptor 2–negative, cT1c-cT4c, cN0/+) were randomly assigned to A: nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly (q3w); vs B: nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w. The trial was powered for a pCR (ypT0/is ypN0) comparison by therapy arm and early response (defined as Ki-67 decrease >30% or < 500 invasive tumor cells in the three-week serial biopsy). All statistical tests were two-sided. Results
A total of 336 patients were enrolled (48 centers, arms A/B: n = 182/154). The median age was 50 years. At baseline (A vs B), 62.6% and 62.9% had cT2–4c tumors; 86.8% and 90.9% completed therapy per protocol, respectively. pCR favored arm B (28.7%, 95% CI = 0.22 to 0.36, vs 45.9%, 95% CI = 0.38 to 0.54; 95% CI(dBA) = 6.2% to 27.9%, P = .002) and was lower in nonresponders than in early responders (19.5% vs 44.4%, P < .001) or in patients with unclassifiable early response (50.0%). The nab-paclitaxel/gemcitabine was associated with more frequent dose reductions (20.6% vs 11.9%, P = .04), treatment-related serious adverse events (11.1% vs 5.3%, P = .07), grade 3–4 infections (7.2% vs 2.6%, P = .07), and grade 3–4 ALAT elevations (11.7 vs 3.3%, P = .01). Conclusions
This first large randomized trial suggests high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel/carboplatin regimen, superior to nab-paclitaxel/gemcitabine in TNBC. De-escalation of further chemotherapy in patients with early pCR after a short anthracycline-free regimen is a promising field of future research. Early necrotic morphological changes and/or proliferation decrease after the first therapy cycle seem to be associated with subsequent pCR.http://ift.tt/2j8CF2N
Familial Cancer Clustering in Urothelial Cancer: A Population-Based Case–Control Study
Abstract
Background
Family history of bladder cancer confers an increased risk for concordant and discordant cancers in relatives. However, previous studies investigating this relationship lack any correction for smoking status of family members. We conducted a population-based study of cancer risks in relatives of bladder cancer patients and matched controls with exclusion of variant subtypes to improve the understanding of familial cancer clustering. Methods
Case subjects with urothelial carcinoma were identified using the Utah Cancer Registry and matched 1:5 to cancer-free controls from the Utah Population Database. Cox regression was used to determine the risk of cancer in first-degree relatives, second-degree relatives, first cousins, and spouses. A total of 229 251 relatives of case subjects and 1 197 552 relatives of matched control subjects were analyzed. To correct for smoking status, we performed a secondary analysis excluding families with elevated rates of smoking-related cancers. All statistical tests were two-sided. Results
First- and second-degree relatives of case subjects had an increased risk for any cancer diagnosis (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 1.03 to 1.09, P < .001; HR = 1.04, 95% CI = 1.02 to 1.07, P = .001) and urothelial cancer (HR = 1.73, 95% CI = 1.50 to 1.99, P < .001; HR = 1.35, 95% CI = 1.21 to 1.51, P < .001). Site-specific analysis found increased risk for bladder (HR = 1.69, 95% CI = 1.47 to 1.95, P < .001), kidney (HR = 1.30, 95% CI = 1.08 to 1.57, P = .006), cervical (HR = 1.25, 95% CI = 1.06 to 1.49, P = .01), and lung cancer (HR = 1.34, 95% CI = 1.19 to 1.51, P < .001) in first-degree relatives. Second-degree relatives had increased risk for bladder (HR = 1.35, 95% CI = 1.2 to 1.5, P < .001) and thyroid cancer (HR = 1.18, 95% CI = 1.03 to 1.35, P = .02). Spouses showed an increased risk for laryngeal (HR = 2.68, 95% CI = 1.02 to 7.05, P = .04) and cervical cancer (HR = 1.57, 95% CI = 1.13 to 2.17, P = .007). These results did not substantively change after correction for suspected smoking behaviors. Conclusion
Our results suggest familial urothelial cancer clustering independent of smoking, with increased risk in relatives for both concordant and discordant cancers, suggesting shared genetic or environmental roots. Identifying families with statistically significant risks for non-smoking-related urothelial cancer would be extremely informative for genetic linkage studies.http://ift.tt/2j87PHs
Updates to the National Cancer Institute’s PDQ Information from Recently Published Oncology Research
PDQ (Physician Data Query) is the National Cancer Institute's source of comprehensive cancer information. It contains peer-reviewed, evidence-based cancer information summaries on treatment, supportive care, screening, prevention, genetics, and complementary and alternative medicine. The summaries are regularly updated by six editorial boards. The following PDQ summaries were recently updated:
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The Moonshot Initiative and the Future of Cancer Research
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An unusual presentation of eosinophilic angiocentric fibrosis
Abstract
Eosinophilic angiocentric fibrosis (EAF) is a rare, benign condition affecting the respiratory mucosa and is generally characterized by a locally destructive growth. We present a case of a lady with a saddle nose deformity that had for many years been treated as granulomatosis with polyangiitis (GPA), of which saddle nose deformity is a classic feature. At the time of surgery, she was found to have subglottic stenosis another classic feature of GPA, however, histology demonstrated EAF. We discuss the difference between the two conditions and highlight the importance of making the correct diagnosis.http://ift.tt/2nI0Qqm
Hepatic portal venous gas: acute deterioration in an elderly patient
Abstract
A 91-year-old female presented to the Emergency Department with a 10-day history of constipation and abdominal pain. Abdominal examination was normal and rectal examination showed faecal loading. A phosphate enema was given and the patient was admitted. Overnight, the patient's GCS dropped from 15/15 to 3/15 and an arterial blood gas showed a lactate of 8 mmol/L (1.5 on admission). Abdomen remained soft throughout. A CT scan showed a large amount of free air and free fluid within the abdomen and pelvis, highly suspicious for perforation. Hepatic portal venous gas (HPVG) was visible, with portal venous air fluid levels noted. The patient was treated palliatively and died shortly thereafter. HPVG is a recognized but rarely identified radiological sign, which is a poor prognostic indicator, with most cases subsequently proving terminal, often due to subsequent bowel necrosis.http://ift.tt/2kc2RpC
Severe Fournier’s gangrene—a conjoint challenge of gynaecology and plastic surgery
Abstract
Necrotizing fasciitis (NF) is a rare soft tissue infection characterized by rapidly progressing necroses and a high mortality. Prompt diagnosis and immediate medical treatment including radical debridement and broad spectrum antibiotics are the key to successful management. We report on a 46-year-old diabetic female who developed extensive, deep necroses in the perineal area and proximal thighs within a few days. After initial gynaecological consultation, she was transferred directly to our department. Due to the suspicion of NF, an immediate radical debridement was performed. Two more debridements were necessary to control the infection. After stabilization, the extensive soft tissue defect was reconstructed using a combination of plastic reconstructive procedures. Due to early diagnosis, direct referral and immediate surgical treatment, the patient survived.http://ift.tt/2kcKsZJ
Tumor Infiltrating Lymphocytes in Breast Cancer Patients with Progressive Disease during Neoadjuvant Chemotherapy
Abstract
A minority of breast cancer (BC) patients progress during neoadjuvant chemotherapy (NCT). The aim of this study was to assess the value of Tumor infiltrating lymphocytes (TILs) in such a high-risk population where valid biomarkers are eagerly needed. A retrospective review identified BC patients who either progressed during NCT or achieved a pathologic complete response (pCR). An experienced BC pathologist semi-quantified stromal TILs in pre-treatment core biopsies using hematoxylin and eosin stained slides. The primary outcome was to compare the levels of TILs between the 2 groups as a continuous and categorical variable using the t-test and X2 test as appropriate. The secondary outcome was to compare survival outcomes between patients with high versus low TILs level using the log-rank test. Fifty patients were successfully identified and assessed for TILs: 21 progressed during NCT and 29 had a pCR. Patients with progressive disease were older with more advanced disease (p = 0.03, p = 0.0001 respectively). A significantly lower mean level of TILs was found in patients with progressive disease compared to patients with pCR: 14.3% (Standard Deviation (SD): 16.9) versus 32.8% (SD: 31), p = 0.01). The level of TILs was neither associated with baseline characteristics nor with survival outcomes. BC patients progressing during NCT have low TILs levels compared to patients with pCR. Prospective studies are needed to establish the utility of TILs as early biomarkers of tumor response, particularly in patients with disease progression who need novel treatment approaches.
http://ift.tt/2j8Aah8
ÖGRO survey on radiotherapy capacity in Austria
Abstract
Background
A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO).
Materials and methods
All Austrian centers provided data on the number of megavoltage (MV) units, treatment series, fractions, percentage of retreatments and complex treatment techniques as well as the daily operating hours for the year 2014. In addition, waiting times until the beginning of radiotherapy were prospectively recorded over the first quarter of 2015. National and international epidemiological prediction data were used to estimate future demands.
Results
For a population of 8.51 million, 43 MV units were at disposal. In 14 radiooncological centers, a total of 19,940 series with a mean number of 464 patients per MV unit/year and a mean fraction number of 20 (range 16–24) per case were recorded. The average re-irradiation ratio was 14%. The survey on waiting times until start of treatment showed provision shortages in 40% of centers with a mean waiting time of 13.6 days (range 0.5–29.3 days) and a mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a limited ability to deliver complex treatment techniques. Predictions for 2020 and 2030 indicate an increased need in the overall number of MV units to a total of 63 and 71, respectively.
Conclusion
This ÖGRO survey revealed major regional differences in radiooncological capacity. Considering epidemiological developments, an aggravation of the situation can be expected shortly. This analysis serves as a basis for improved public regional health care planning.
http://ift.tt/2kE6XLi
Tumor Infiltrating Lymphocytes in Breast Cancer Patients with Progressive Disease during Neoadjuvant Chemotherapy
Abstract
A minority of breast cancer (BC) patients progress during neoadjuvant chemotherapy (NCT). The aim of this study was to assess the value of Tumor infiltrating lymphocytes (TILs) in such a high-risk population where valid biomarkers are eagerly needed. A retrospective review identified BC patients who either progressed during NCT or achieved a pathologic complete response (pCR). An experienced BC pathologist semi-quantified stromal TILs in pre-treatment core biopsies using hematoxylin and eosin stained slides. The primary outcome was to compare the levels of TILs between the 2 groups as a continuous and categorical variable using the t-test and X2 test as appropriate. The secondary outcome was to compare survival outcomes between patients with high versus low TILs level using the log-rank test. Fifty patients were successfully identified and assessed for TILs: 21 progressed during NCT and 29 had a pCR. Patients with progressive disease were older with more advanced disease (p = 0.03, p = 0.0001 respectively). A significantly lower mean level of TILs was found in patients with progressive disease compared to patients with pCR: 14.3% (Standard Deviation (SD): 16.9) versus 32.8% (SD: 31), p = 0.01). The level of TILs was neither associated with baseline characteristics nor with survival outcomes. BC patients progressing during NCT have low TILs levels compared to patients with pCR. Prospective studies are needed to establish the utility of TILs as early biomarkers of tumor response, particularly in patients with disease progression who need novel treatment approaches.
http://ift.tt/2j8Aah8
Characterizing the neighborhood obesogenic environment in the Multiethnic Cohort: a multi-level infrastructure for cancer health disparities research
Abstract
Purpose
We characterized the neighborhood obesogenic environment in the Multiethnic Cohort (MEC) by examining the associations of obesity with attributes of the social and built environment, establishing a multi-level infrastructure for future cancer research.
Methods
For 102,906 African American, Japanese American, Latino, and white MEC participants residing predominately in Los Angeles County, baseline residential addresses (1993–1996) were linked to census and geospatial data, capturing neighborhood socioeconomic status (nSES), population density, commuting, food outlets, amenities, walkability, and traffic density. We examined neighborhood attributes and obesity (body mass index ≥ 30 kg/m2) associations using multinomial logistic regression, adjusting for individual-level (e.g., demographics, physical activity, and diet) and neighborhood-level factors.
Results
NSES was associated with obesity among African Americans, Latinos, and whites (p-trend ≤ 0.02), with twofold higher odds (adjusted odds ratios, 95% confidence intervals) for living in the lowest versus highest quintile among African American women (2.07, 1.62–2.65), white men (2.11, 1.29–3.44), and white women (2.50, 1.73–3.61). Lower density of businesses among African American and white women and lower traffic density among white men were also associated with obesity (p-trends ≤ 0.02).
Conclusions
Our study highlights differential impacts of neighborhood factors across racial/ethnic groups and establishes the foundation for multi-level studies of the neighborhood context and obesity-related cancers.
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Characterizing the neighborhood obesogenic environment in the Multiethnic Cohort: a multi-level infrastructure for cancer health disparities research
Abstract
Purpose
We characterized the neighborhood obesogenic environment in the Multiethnic Cohort (MEC) by examining the associations of obesity with attributes of the social and built environment, establishing a multi-level infrastructure for future cancer research.
Methods
For 102,906 African American, Japanese American, Latino, and white MEC participants residing predominately in Los Angeles County, baseline residential addresses (1993–1996) were linked to census and geospatial data, capturing neighborhood socioeconomic status (nSES), population density, commuting, food outlets, amenities, walkability, and traffic density. We examined neighborhood attributes and obesity (body mass index ≥ 30 kg/m2) associations using multinomial logistic regression, adjusting for individual-level (e.g., demographics, physical activity, and diet) and neighborhood-level factors.
Results
NSES was associated with obesity among African Americans, Latinos, and whites (p-trend ≤ 0.02), with twofold higher odds (adjusted odds ratios, 95% confidence intervals) for living in the lowest versus highest quintile among African American women (2.07, 1.62–2.65), white men (2.11, 1.29–3.44), and white women (2.50, 1.73–3.61). Lower density of businesses among African American and white women and lower traffic density among white men were also associated with obesity (p-trends ≤ 0.02).
Conclusions
Our study highlights differential impacts of neighborhood factors across racial/ethnic groups and establishes the foundation for multi-level studies of the neighborhood context and obesity-related cancers.
http://ift.tt/2jv4242
Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage IV neck node-positive head and neck cancer and a good performance status
Abstract
Purpose
The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most.
Methods
A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m2 IV) and cisplatin (75 mg/m2 IV) on day 1 plus 5-FU (750 mg/m2 IV) on days 2–5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m2 IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor.
Results
Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis.
Conclusion
With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation.
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via IFTTT
Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage IV neck node-positive head and neck cancer and a good performance status
Abstract
Purpose
The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most.
Methods
A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m2 IV) and cisplatin (75 mg/m2 IV) on day 1 plus 5-FU (750 mg/m2 IV) on days 2–5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m2 IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor.
Results
Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis.
Conclusion
With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation.
http://ift.tt/2kbwwiI
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