Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

Abstract

Purpose of Review

We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients.

Recent Findings

Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases.

Summary

Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.

from Cancer via ola Kala on Inoreader http://ift.tt/2ysJUbY
via IFTTT

Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

Abstract

Purpose of Review

We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients.

Recent Findings

Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases.

Summary

Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.

http://ift.tt/2ysJUbY

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15–55 years of age

Abstract

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15–25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26–45-year olds and 45–55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15–25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15–55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.

The HPV-16/18 AS04-adjuvanted vaccine produced a sustained immune response in women aged 15–55 years at vaccination for up to 10 years, with an acceptable safety profile. Study results suggest that women in age groups not targeted by adolescent immunization and catch-up programs may still individually benefit from HPV vaccination.

http://ift.tt/2z1DzkS

Inhibition of telomerase activity and induction of apoptosis by Rhodospirillum rubrum L-asparaginase in cancer Jurkat cell line and normal human CD4+ T lymphocytes

Abstract

Rhodospirillum rubrum L-asparaginase mutant _{E149R, V150P, F151T} (RrA) down-regulates telomerase activity due to its ability to inhibit the expression of telomerase catalytic subunit hTERT. The aim of this study was to define the effect of short-term and long-term RrA exposure on proliferation of cancer Jurkat cell line and normal human CD4⁺ T lymphocytes. RrA could inhibit telomerase activity in dose- and time-dependent manner in both Jurkat and normal CD4⁺ T cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell cycle inhibition, replicative senescence, and development of apoptosis. Complete death of Jurkat cells was observed at the day 25 of RrA exposure while normal CD4⁺ T cells died at the day 50 due to the initial longer length of telomeres. Removal of RrA from senescent cells led to a reactivation of hTERT expression, restoration telomerase activity, re-elongation of telomeres after 48 h of cultivation, and survival of cells. These findings demonstrate that proliferation of cancer and normal telomerase-positive cells can be limited by continuous telomerase inhibition with RrA. Longer telomeres of normal CD4⁺ T lymphocytes make such cells more sustainable to RrA exposure that could give them an advantage during anti-telomerase therapy. These results should facilitate further investigations of RrA as a potent anti-telomerase therapeutic protein.

Long-term exposure to Rhodospirillum rubrum L-asparaginase (RrA) induced telomere shortening and eventual growth arrest and apoptosis in vitro. Telomerase inhibition using RrA may be considered as a promising approach for cancer treatment.

http://ift.tt/2y56vKA

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15–55 years of age

Abstract

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15–25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26–45-year olds and 45–55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15–25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15–55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.

The HPV-16/18 AS04-adjuvanted vaccine produced a sustained immune response in women aged 15–55 years at vaccination for up to 10 years, with an acceptable safety profile. Study results suggest that women in age groups not targeted by adolescent immunization and catch-up programs may still individually benefit from HPV vaccination.

from Cancer via ola Kala on Inoreader http://ift.tt/2z1DzkS
via IFTTT

Inhibition of telomerase activity and induction of apoptosis by Rhodospirillum rubrum L-asparaginase in cancer Jurkat cell line and normal human CD4+ T lymphocytes

Abstract

Rhodospirillum rubrum L-asparaginase mutant _{E149R, V150P, F151T} (RrA) down-regulates telomerase activity due to its ability to inhibit the expression of telomerase catalytic subunit hTERT. The aim of this study was to define the effect of short-term and long-term RrA exposure on proliferation of cancer Jurkat cell line and normal human CD4⁺ T lymphocytes. RrA could inhibit telomerase activity in dose- and time-dependent manner in both Jurkat and normal CD4⁺ T cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell cycle inhibition, replicative senescence, and development of apoptosis. Complete death of Jurkat cells was observed at the day 25 of RrA exposure while normal CD4⁺ T cells died at the day 50 due to the initial longer length of telomeres. Removal of RrA from senescent cells led to a reactivation of hTERT expression, restoration telomerase activity, re-elongation of telomeres after 48 h of cultivation, and survival of cells. These findings demonstrate that proliferation of cancer and normal telomerase-positive cells can be limited by continuous telomerase inhibition with RrA. Longer telomeres of normal CD4⁺ T lymphocytes make such cells more sustainable to RrA exposure that could give them an advantage during anti-telomerase therapy. These results should facilitate further investigations of RrA as a potent anti-telomerase therapeutic protein.

Long-term exposure to Rhodospirillum rubrum L-asparaginase (RrA) induced telomere shortening and eventual growth arrest and apoptosis in vitro. Telomerase inhibition using RrA may be considered as a promising approach for cancer treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/2y56vKA
via IFTTT

Deep Learning based multi-omics integration robustly predicts survival in liver cancer

Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill in this gap, we present a deep learning (DL) based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We build the DL based, survival-sensitive model on 360 HCC patients' data using RNA-seq, miRNA-seq and methylation data from TCGA, which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL based model provides two optimal subgroups of patients with significant survival differences (P=7.13e-6) and good model fitness (C-index=0.68). More aggressive subtype is associated with frequent TP53 inactivation mutations, higher expression of stemness markers (KRT19, EPCAM) and tumor marker BIRC5, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (n=230, C-index=0.75), NCI cohort (n=221, C-index=0.67), Chinese cohort (n=166, C-index=0.69), E-TABM-36 cohort (n=40, C-index=0.77), and Hawaiian cohort (n=27, C-index=0.82). This is the first study to employ deep learning to identify multi-omics features linked to the differential survival of HCC patients. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction.

http://ift.tt/2xlDye4

FDA Approves First Biosimilar to Treat Cancer [News in Brief]

Like the related agent bevacizumab, the drug can be used to treat multiple types of cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2fXQhMF
via IFTTT

Deep Learning based multi-omics integration robustly predicts survival in liver cancer

Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill in this gap, we present a deep learning (DL) based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We build the DL based, survival-sensitive model on 360 HCC patients' data using RNA-seq, miRNA-seq and methylation data from TCGA, which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL based model provides two optimal subgroups of patients with significant survival differences (P=7.13e-6) and good model fitness (C-index=0.68). More aggressive subtype is associated with frequent TP53 inactivation mutations, higher expression of stemness markers (KRT19, EPCAM) and tumor marker BIRC5, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (n=230, C-index=0.75), NCI cohort (n=221, C-index=0.67), Chinese cohort (n=166, C-index=0.69), E-TABM-36 cohort (n=40, C-index=0.77), and Hawaiian cohort (n=27, C-index=0.82). This is the first study to employ deep learning to identify multi-omics features linked to the differential survival of HCC patients. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction.

from Cancer via ola Kala on Inoreader http://ift.tt/2xlDye4
via IFTTT

Therapy for Chronic Myelomonocytic Leukemia in a New Era

Abstract

Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined. Conventional treatments include hydroxyurea, cytarabine, and hypomethylating agents. However, all treatment options are limited and, with the exception of allogeneic stem cell transplantation, are considered palliative. As we continue to learn about the genomics of CMML and about arising therapeutic targets and those under active clinical investigation, the future therapy of CMML will likely improve considerably. Here, we review the data available for conventional therapies and highlight emerging therapeutic strategies.

http://ift.tt/2fVdDmk

Therapy for Chronic Myelomonocytic Leukemia in a New Era

Abstract

Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined. Conventional treatments include hydroxyurea, cytarabine, and hypomethylating agents. However, all treatment options are limited and, with the exception of allogeneic stem cell transplantation, are considered palliative. As we continue to learn about the genomics of CMML and about arising therapeutic targets and those under active clinical investigation, the future therapy of CMML will likely improve considerably. Here, we review the data available for conventional therapies and highlight emerging therapeutic strategies.

from Cancer via ola Kala on Inoreader http://ift.tt/2fVdDmk
via IFTTT

Genetic Variations of DNA Repair Genes in Breast Cancer

Abstract

Genetic variations in DNA repair genes may affect DNA repair capacity therefore increase risk for cancer. In our study, we evaluted the relation between DNA repair gene polymorphisms XRCC1 rs1799782, rs25487, rs25489; XPC rs2228000, rs2228001; XPD rs1799793, rs13181; XRCC3 rs861539; RAD51B rs10483813, rs1314913 and breast cancer risk for 202 Turkish cases in total, in which 102 patients with breast cancer and 100 controls. Genotyping of the DNA samples was carried out by multiplex PCR and matrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) using Sequenom MassARRAY 4 analyzer. Genotype and allele distributions were calculated between the groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. rs25487 AA genotype and A allele was found to be increased in the control group (respectively, OR 0.16 95% CI 0.02–1.06, p = 0.058; OR 1.55, 95% CI 1.01–2.36, p = 0.043) and rs861539 T allele was found to be decreased in the patient group (OR 1.53, 95% CI 1.01–2.30, p = 0.049). No association with breast cancer was found for the remaining SNPs. Our findings suggest that XRCC1 rs25487 AA genotype and A allele, XRCC3 rs861539 T allele may have protective effects in breast cancer for Turkish population.

http://ift.tt/2xXfU4H

Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated?

Abstract

Background

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with impaired social interactions and communication and restrictive, repetitive patterns of behaviors, interests, and activities. A recent epidemiological study suggests that children with ASD might have an increased cancer risk.

Case presentation

The 14.5-year-old boy, previously diagnosed with ASD, was referred with persistent bone pain. Diagnostic work-up confirmed diagnosis of acute lymphoblastic leukemia (ALL); cytogenetic analysis revealed low hypodiploid karyotype with a mutation (c.733G>A, p.Gly245Ser, rs28934575) in TP53 in the leukemic blasts. By Sanger sequencing, the presence of this mutation in the germline was subsequently confirmed and, thus, diagnosis of Li-Fraumeni syndrome (LFS) was made. His family history was remarkable with two siblings with intellectual disability and a mother who has died of premenopausal breast cancer.

Conclusions

Some of the oncogenes and tumor suppressor genes causing cancer susceptibility syndromes overlap with those involved in autism. This functional overlap between autism and cancer is novel and particularly compelling. The surprising coincidence of LFS and ASD in our patient raises the question whether this is purely coincidental or mechanistically associated.

from Cancer via ola Kala on Inoreader http://ift.tt/2yLs4gr
via IFTTT

Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated?

Abstract

Background

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with impaired social interactions and communication and restrictive, repetitive patterns of behaviors, interests, and activities. A recent epidemiological study suggests that children with ASD might have an increased cancer risk.

Case presentation

The 14.5-year-old boy, previously diagnosed with ASD, was referred with persistent bone pain. Diagnostic work-up confirmed diagnosis of acute lymphoblastic leukemia (ALL); cytogenetic analysis revealed low hypodiploid karyotype with a mutation (c.733G>A, p.Gly245Ser, rs28934575) in TP53 in the leukemic blasts. By Sanger sequencing, the presence of this mutation in the germline was subsequently confirmed and, thus, diagnosis of Li-Fraumeni syndrome (LFS) was made. His family history was remarkable with two siblings with intellectual disability and a mother who has died of premenopausal breast cancer.

Conclusions

Some of the oncogenes and tumor suppressor genes causing cancer susceptibility syndromes overlap with those involved in autism. This functional overlap between autism and cancer is novel and particularly compelling. The surprising coincidence of LFS and ASD in our patient raises the question whether this is purely coincidental or mechanistically associated.

http://ift.tt/2yLs4gr

Genetic Variations of DNA Repair Genes in Breast Cancer

Abstract

Genetic variations in DNA repair genes may affect DNA repair capacity therefore increase risk for cancer. In our study, we evaluted the relation between DNA repair gene polymorphisms XRCC1 rs1799782, rs25487, rs25489; XPC rs2228000, rs2228001; XPD rs1799793, rs13181; XRCC3 rs861539; RAD51B rs10483813, rs1314913 and breast cancer risk for 202 Turkish cases in total, in which 102 patients with breast cancer and 100 controls. Genotyping of the DNA samples was carried out by multiplex PCR and matrix-assisted laser desorption/ionization mass spectrometry with time of flight measurement (MALDI-TOF) using Sequenom MassARRAY 4 analyzer. Genotype and allele distributions were calculated between the groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. rs25487 AA genotype and A allele was found to be increased in the control group (respectively, OR 0.16 95% CI 0.02–1.06, p = 0.058; OR 1.55, 95% CI 1.01–2.36, p = 0.043) and rs861539 T allele was found to be decreased in the patient group (OR 1.53, 95% CI 1.01–2.30, p = 0.049). No association with breast cancer was found for the remaining SNPs. Our findings suggest that XRCC1 rs25487 AA genotype and A allele, XRCC3 rs861539 T allele may have protective effects in breast cancer for Turkish population.

http://ift.tt/2xXfU4H

Utility of adult-based ultrasound malignancy risk stratifications in pediatric thyroid nodules

Abstract

Background

Individual ultrasound (US) features have limited ability to distinguish benign from malignant thyroid nodules. Adult-based systems have been developed to integrate the sonographic features in an effort to improve diagnostic accuracy. None, however, has been validated in children, in whom the likelihood of malignancy is 2–5 times higher than adults.

Objective

To assess the performance of two adult-based sonographic (US) stratification methods for assessment of thyroid nodules in children.

Materials and methods

This retrospective study comprised 124 children who underwent thyroid US. Three radiologists reviewed the US data using the American Thyroid Association (ATA) and the Thyroid Image Reporting and Data System (TI-RADS). Radiologists' accuracy and agreement was assessed. The reference standard was histopathology/cytology or 2-year follow-up of clinical outcome for nonoperative cases.

Results

We assessed 71 benign and 52 malignant nodules and excluded 1 nodule. Using the ATA pattern descriptions, 80% of malignant nodules were classified as "high" 36/52 (69%) or "intermediate" 6/52 (11%) likelihood of malignancy. A total of 20/71 (28%) benign nodules were also classified within these two categories. Using the TI-RADS, malignant nodules were classified as 2, 3, 4a, 4b, 4c and 5, with rate of malignancy of 0%, 0%, 7/52 (13.5%), 7/52 (13.5%), 32/52 (61.5%) and 6/52 (11.5%), respectively. Benign nodules were also classified in the 4a (26/71; 36.6%), 4b (17/71; 24%), 4c (14/71; 19.7%) and 5 (1/71; 1.4%) categories. The positive and negative predictive values were 68.0% and 87.5% for ATA, and 71.7% and 80.0% for TI-RADS.

Conclusion

We validated the use of ATA and TI-RADS methods in children and showed that they have test characteristics similar to those in adults, although neither is independently sufficient to discriminate nodules' likelihood of malignancy.

http://ift.tt/2ytRwL6

Nitric Oxide (Donor/Induced) in Chemosensitization, Volume 1. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2fOBLmP
via IFTTT

Applications of Mass Spectrometry Imaging to Cancer, Volume 134. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2yKxatk
via IFTTT

Cancer Disparities, Volume 133. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2fOdxZU
via IFTTT

Ecology and Evolution of Cancer. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2yLbehF
via IFTTT

Handbook of Supportive and Palliative Radiation Oncology

from Cancer via ola Kala on Inoreader http://ift.tt/2fMIOMS
via IFTTT

Congenital and Acquired Bone Marrow Failure. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2yLKFZE
via IFTTT

Thyroid Cancer and Nuclear Accidents. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2fMII7Y
via IFTTT

Patient-Derived Mouse Models of Cancer. Patient-Derived Orthotopic Xenografts (PDOX)

from Cancer via ola Kala on Inoreader http://ift.tt/2yKV488
via IFTTT

Molecular Approach to Cancer Management. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2fOdwVQ
via IFTTT

Translational Advances in Gynecologic Cancers. 1st Edition

from Cancer via ola Kala on Inoreader http://ift.tt/2yLStui
via IFTTT

Differential Prognostic Value of Metabolic Heterogeneity of Primary Tumor and Metastatic Lymph Nodes in Patients with Pharyngeal Cancer

Background/Aim: We aimed to explore the prognostic value of metabolic heterogeneity of ¹⁸F-FDG uptake in chemoradiotherapy-treated pharyngeal cancer patients. Patients and Methods: This study included 52 consecutive patients with pharyngeal cancer who underwent ¹⁸F-FDG PET/CT before definitive chemoradiotherapy. The heterogeneity factor (HF) was defined as the derivative (dV/dT) of a volume-threshold function for primary tumors and metastatic lymph nodes. The relationships between clinical parameters and HFs of primary tumors (pHF) and metastatic lymph nodes (nHF) were analyzed. Results: The pHF (range=1.367 - –0.027; median=–0.152) was significantly correlated with the maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis. Induction chemotherapy response was not correlated with HF, whereas response to radiotherapy was significantly better in patients with high pHF (low heterogeneity). Consistently, the 2-year locoregional recurrence-free survival was significantly better in patients with high pHF (82.9% for pHF>–0.152 vs. 30.5% for pHF<–0.152, log-rank p=0.009). The nHF (range=–1.067 - –0.039; median=-0.160) was not correlated with response to radiotherapy and locoregional recurrences. Conclusion: pHF, but not nHF, was a significant predictor of response to radiotherapy and locoregional recurrence in pharyngeal cancer. Thus, HF use can prevent unnecessary treatment and surgical delays.

from Cancer via ola Kala on Inoreader http://ift.tt/2fOp9fo
via IFTTT

Gastric Spindle Cell Neuroendocrine Tumor Mimicking Gastrointestinal Stromal Tumor: Unique Morphology and Diagnostic Pitfall

Gastric neuroendocrine tumors (GNETs) with spindle cell morphology are extremely rare. We present a case of a 49-year-old female patient with a history of systemic lupus erythematosus, Sjogren's syndrome, and gastroesophageal reflux disease. She was initially thought to have a spindle cell gastrointestinal stromal tumor per histological studies of the fundic polypectomy samples. Immunohistochemically, the tumor cells were negative for CD117, and CD34, but positive for chromogranin, synaptophysin, and CD56 with a 6% Ki-67 index, consistent with a spindle cell-type well differentiated neuroendocrine tumor, World Health Organization (WHO) Grade 2. To the best of our knowledge, this is the first case report of a gastric spindle cell neuroendocrine tumor in the English literature.

from Cancer via ola Kala on Inoreader http://ift.tt/2yKx98K
via IFTTT

Book Reviews

from Cancer via ola Kala on Inoreader http://ift.tt/2fPgv02
via IFTTT

miR-223 and Stathmin-1 Expression in Non-tumor Liver Tissue of Patients with Hepatocellular Carcinoma

Aim: Overexpression of stathmin (STMN1) has been reported for several tumor entities. STMN1 expression correlated with the detection of mutant p53, also suggesting loss-of-function-dependent mechanisms for its accumulation in hepatocellular carcinoma (HCC) cells. On the other hand, miR-223 has been identified as one of the most down-regulated miRNAs in HCC, and its expression was shown to be negatively correlated with STMN1 expression. The aim of this study was to investigate the clinical significance of STMN1 and miRNA-223 expression. Patients and Methods: Fifty-six consecutive patients with HCC who underwent curative hepatectomy as initial treatment were enrolled. They were divided into two groups based on the STMN1 expression level: high (n=36) and low (n=20) gene-expression groups. We compared the clinicopathological factors between the groups with high and low expression in non-tumor tissues. Thirty out of 56 patients were also divided into groups with high (n=15) and low (n=15) miR-223 expression and compared the clinicopathological factors between the two groups. Results: There were no significant differences in patient background between high and low STMN1 expression groups. The incidence of multicentric (MC) recurrence in the high-expression group was significantly higher than in the low-expression group and high STMN1 expression was shown to be an independent risk factor for MC recurrence. There were also no significant differences in patient background between high and low miR-223 expression groups; however, the disease-free survival rate in the group with low expression was significantly worse. Furthermore, MC-related miRNAs identified by miRNA microarray clearly clustered patients into MC recurrence and non-recurrence groups. Conclusion: Both gene and miRNA expression profiles in non-tumor liver tissues could predict the risk for MC recurrence. Such molecular information may be useful in enabling better decision making for patients with HCC.

from Cancer via ola Kala on Inoreader http://ift.tt/2yKOEpw
via IFTTT

Surgical Resection and Outcome of Synchronous and Metachronous Primary Lung Cancer in Breast Cancer Patients

Background/Aim: Women with breast cancer are at increased risk of subsequent primary malignancies, specifically lung cancer. The aim of this study was to report the frequency of lung cancer in patients with breast cancer, and patients' characteristics and surgical outcomes. Patients and Methods: We investigated 1,066 consecutive female patients undergoing surgical resection for breast cancer and 666 undergoing surgical resection for lung cancer. Results: Lung cancer with breast cancer was observed in 14 patients (1.3% of breast cancer and 2.1% of lung cancer cases; mean age=65 years), and 3/14 (21.4%) patients were smokers. Sixteen lung cancer lesions in 14 patients were adenocarcinomas and one was squamous cell carcinoma. All 14 patients were alive at the time of this report; 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) had recurrent lung cancer. In synchronous cases, 5/6 (83.3%) patients received concomitant surgery for both breast cancer and lung cancer. Patients' postoperative courses were uneventful. In metachronous cases, eight patients had lung cancer a mean of 33 months after breast cancer surgery. All eight patients received adjuvant therapies and 4/8 (50%) patients received adjuvant therapies for recurrent breast cancer, including chemotherapy, radiotherapy, hormonal therapy, and anti-HER2 therapy. All patients had early-stage lung adenocarcinoma and underwent surgical resection. Conclusion: Concomitant surgery for synchronous lung and breast cancer was feasible and safe. In metachronous cases, lung cancers tended to be detected within 3 years after surgery for breast cancer. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2fMIu0C
via IFTTT

The Association Between Chemotherapy Immediately Before Nivolumab and Outcomes Thereafter

Background/Aim: We investigated whether the efficacy and type of pre-nivolumab chemotherapy influence outcomes in non-small cell lung cancer patients following nivolumab treatment. Patients and Methods: In this multicenter study, 199 patients treated with nivolumab were retrospectively reviewed. We analyzed the relationships between the clinical response to nivolumab and to chemotherapy administered immediately beforehand. Results: Patients who achieved objective responses to pretreatments showed higher disease control rates with nivolumab than patients who did not (64% vs. 47%, p=0.03), as did those who achieved disease control with pretreatments (62% vs. 35%, p<0.001). Bevacizumab-pretreated patients tended to show better objective response rates with nivolumab (27% vs. 13%, p=0.06); the objective response rate to nivolumab was significantly higher in bevacizumab-pretreated patients who showed clinical responses (42% vs. 9.1%, p=0.02). Conclusion: Achievement of a clinical response to chemotherapy immediately before nivolumab, particularly when combined with bevacizumab, increases the likelihood of disease control post-nivolumab.

from Cancer via ola Kala on Inoreader http://ift.tt/2yMinOM
via IFTTT

Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab

Background: Nivolumab has shown promising effects in patients with non-small-cell lung cancer (NSCLC) as a second- or later-line treatment. This study aimed to identify patients who would not experience any benefit from nivolumab treatment. Materials and Methods: In this study, data for 201 patients treated with nivolumab during 17 December 2015 to 31 July 2016 at three respiratory medical centers in Japan were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment commencement. We investigated the relationship between progression-free survival (PFS) and patient characteristics. Results: In both univariate and multivariate analysis, performance status (PS) score ≥2, steroid use at baseline and lactate dehydrogenase (LDH) level >240 IU/l were significantly associated with poor PFS (all p<0.05). Conclusion: PS score ≥2, steroid use at baseline and a high LDH level were predictive of poor PFS in patients with NSCLC treated with nivolumab. Careful monitoring is recommended for treating such patients with nivolumab (UMIN-ID: UMIN000025908).

from Cancer via ola Kala on Inoreader http://ift.tt/2fMIpdk
via IFTTT

A Proposal for Progression-Free Survival Assessment in Patients with Early Progressive Cancer

Background/Aim: Progression-free survival (PFS), which is evaluated in oncology clinical trials, is determined based on tumor progression evaluated according to an assessment schedule. There is possibly a bias in median PFS and hazard ratio (HR) for PFS depending on the assessment schedule referring to randomized controlled trials (RCTs) in patients with metastatic colorectal cancer. Materials and Methods: We re-analyzed the PFS in the FTD/TPI phase 2 trial by changing the assessment schedule. To assess biases in median PFS and HR for PFS resulting from different assessment schedules, we performed a computational simulation. Results: The reanalysis of FTD/TPI phase 2 trial and the simulation results showed that there were biases in median PFS and HR for PFS. Conclusion: In RCTs for early progressive cancer, median PFS is dependent on the assessment schedule; however, HR for PFS can be assessed without clinically-meaningful differences between assessment schedules, regardless of biomarker assumptions.

from Cancer via ola Kala on Inoreader http://ift.tt/2yKOFtA
via IFTTT

Nitric Oxide (Donor/Induced) in Chemosensitization, Volume 1. 1st Edition

http://ift.tt/2fOBLmP

Ethical Challenges in Oncology. 1st Edition

http://ift.tt/2yLNOsj

Announcements

http://ift.tt/2fMJ2Ue

Applications of Mass Spectrometry Imaging to Cancer, Volume 134. 1st Edition

http://ift.tt/2yKxatk

Cancer Disparities, Volume 133. 1st Edition

http://ift.tt/2fOdxZU

Ecology and Evolution of Cancer. 1st Edition

http://ift.tt/2yLbehF

Handbook of Supportive and Palliative Radiation Oncology

http://ift.tt/2fMIOMS

Congenital and Acquired Bone Marrow Failure. 1st Edition

http://ift.tt/2yLKFZE

Thyroid Cancer and Nuclear Accidents. 1st Edition

http://ift.tt/2fMII7Y

Patient-Derived Mouse Models of Cancer. Patient-Derived Orthotopic Xenografts (PDOX)

http://ift.tt/2yKV488

Molecular Approach to Cancer Management. 1st Edition

http://ift.tt/2fOdwVQ

Translational Advances in Gynecologic Cancers. 1st Edition

http://ift.tt/2yLStui

Differential Prognostic Value of Metabolic Heterogeneity of Primary Tumor and Metastatic Lymph Nodes in Patients with Pharyngeal Cancer

Background/Aim: We aimed to explore the prognostic value of metabolic heterogeneity of ¹⁸F-FDG uptake in chemoradiotherapy-treated pharyngeal cancer patients. Patients and Methods: This study included 52 consecutive patients with pharyngeal cancer who underwent ¹⁸F-FDG PET/CT before definitive chemoradiotherapy. The heterogeneity factor (HF) was defined as the derivative (dV/dT) of a volume-threshold function for primary tumors and metastatic lymph nodes. The relationships between clinical parameters and HFs of primary tumors (pHF) and metastatic lymph nodes (nHF) were analyzed. Results: The pHF (range=1.367 - –0.027; median=–0.152) was significantly correlated with the maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis. Induction chemotherapy response was not correlated with HF, whereas response to radiotherapy was significantly better in patients with high pHF (low heterogeneity). Consistently, the 2-year locoregional recurrence-free survival was significantly better in patients with high pHF (82.9% for pHF>–0.152 vs. 30.5% for pHF<–0.152, log-rank p=0.009). The nHF (range=–1.067 - –0.039; median=-0.160) was not correlated with response to radiotherapy and locoregional recurrences. Conclusion: pHF, but not nHF, was a significant predictor of response to radiotherapy and locoregional recurrence in pharyngeal cancer. Thus, HF use can prevent unnecessary treatment and surgical delays.

http://ift.tt/2fOp9fo

Gastric Spindle Cell Neuroendocrine Tumor Mimicking Gastrointestinal Stromal Tumor: Unique Morphology and Diagnostic Pitfall

Gastric neuroendocrine tumors (GNETs) with spindle cell morphology are extremely rare. We present a case of a 49-year-old female patient with a history of systemic lupus erythematosus, Sjogren's syndrome, and gastroesophageal reflux disease. She was initially thought to have a spindle cell gastrointestinal stromal tumor per histological studies of the fundic polypectomy samples. Immunohistochemically, the tumor cells were negative for CD117, and CD34, but positive for chromogranin, synaptophysin, and CD56 with a 6% Ki-67 index, consistent with a spindle cell-type well differentiated neuroendocrine tumor, World Health Organization (WHO) Grade 2. To the best of our knowledge, this is the first case report of a gastric spindle cell neuroendocrine tumor in the English literature.

http://ift.tt/2yKx98K

Book Reviews

http://ift.tt/2fPgv02

miR-223 and Stathmin-1 Expression in Non-tumor Liver Tissue of Patients with Hepatocellular Carcinoma

Aim: Overexpression of stathmin (STMN1) has been reported for several tumor entities. STMN1 expression correlated with the detection of mutant p53, also suggesting loss-of-function-dependent mechanisms for its accumulation in hepatocellular carcinoma (HCC) cells. On the other hand, miR-223 has been identified as one of the most down-regulated miRNAs in HCC, and its expression was shown to be negatively correlated with STMN1 expression. The aim of this study was to investigate the clinical significance of STMN1 and miRNA-223 expression. Patients and Methods: Fifty-six consecutive patients with HCC who underwent curative hepatectomy as initial treatment were enrolled. They were divided into two groups based on the STMN1 expression level: high (n=36) and low (n=20) gene-expression groups. We compared the clinicopathological factors between the groups with high and low expression in non-tumor tissues. Thirty out of 56 patients were also divided into groups with high (n=15) and low (n=15) miR-223 expression and compared the clinicopathological factors between the two groups. Results: There were no significant differences in patient background between high and low STMN1 expression groups. The incidence of multicentric (MC) recurrence in the high-expression group was significantly higher than in the low-expression group and high STMN1 expression was shown to be an independent risk factor for MC recurrence. There were also no significant differences in patient background between high and low miR-223 expression groups; however, the disease-free survival rate in the group with low expression was significantly worse. Furthermore, MC-related miRNAs identified by miRNA microarray clearly clustered patients into MC recurrence and non-recurrence groups. Conclusion: Both gene and miRNA expression profiles in non-tumor liver tissues could predict the risk for MC recurrence. Such molecular information may be useful in enabling better decision making for patients with HCC.

http://ift.tt/2yKOEpw

Surgical Resection and Outcome of Synchronous and Metachronous Primary Lung Cancer in Breast Cancer Patients

Background/Aim: Women with breast cancer are at increased risk of subsequent primary malignancies, specifically lung cancer. The aim of this study was to report the frequency of lung cancer in patients with breast cancer, and patients' characteristics and surgical outcomes. Patients and Methods: We investigated 1,066 consecutive female patients undergoing surgical resection for breast cancer and 666 undergoing surgical resection for lung cancer. Results: Lung cancer with breast cancer was observed in 14 patients (1.3% of breast cancer and 2.1% of lung cancer cases; mean age=65 years), and 3/14 (21.4%) patients were smokers. Sixteen lung cancer lesions in 14 patients were adenocarcinomas and one was squamous cell carcinoma. All 14 patients were alive at the time of this report; 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) had recurrent lung cancer. In synchronous cases, 5/6 (83.3%) patients received concomitant surgery for both breast cancer and lung cancer. Patients' postoperative courses were uneventful. In metachronous cases, eight patients had lung cancer a mean of 33 months after breast cancer surgery. All eight patients received adjuvant therapies and 4/8 (50%) patients received adjuvant therapies for recurrent breast cancer, including chemotherapy, radiotherapy, hormonal therapy, and anti-HER2 therapy. All patients had early-stage lung adenocarcinoma and underwent surgical resection. Conclusion: Concomitant surgery for synchronous lung and breast cancer was feasible and safe. In metachronous cases, lung cancers tended to be detected within 3 years after surgery for breast cancer. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer.

http://ift.tt/2fMIu0C

The Association Between Chemotherapy Immediately Before Nivolumab and Outcomes Thereafter

Background/Aim: We investigated whether the efficacy and type of pre-nivolumab chemotherapy influence outcomes in non-small cell lung cancer patients following nivolumab treatment. Patients and Methods: In this multicenter study, 199 patients treated with nivolumab were retrospectively reviewed. We analyzed the relationships between the clinical response to nivolumab and to chemotherapy administered immediately beforehand. Results: Patients who achieved objective responses to pretreatments showed higher disease control rates with nivolumab than patients who did not (64% vs. 47%, p=0.03), as did those who achieved disease control with pretreatments (62% vs. 35%, p<0.001). Bevacizumab-pretreated patients tended to show better objective response rates with nivolumab (27% vs. 13%, p=0.06); the objective response rate to nivolumab was significantly higher in bevacizumab-pretreated patients who showed clinical responses (42% vs. 9.1%, p=0.02). Conclusion: Achievement of a clinical response to chemotherapy immediately before nivolumab, particularly when combined with bevacizumab, increases the likelihood of disease control post-nivolumab.

http://ift.tt/2yMinOM

Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab

Background: Nivolumab has shown promising effects in patients with non-small-cell lung cancer (NSCLC) as a second- or later-line treatment. This study aimed to identify patients who would not experience any benefit from nivolumab treatment. Materials and Methods: In this study, data for 201 patients treated with nivolumab during 17 December 2015 to 31 July 2016 at three respiratory medical centers in Japan were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment commencement. We investigated the relationship between progression-free survival (PFS) and patient characteristics. Results: In both univariate and multivariate analysis, performance status (PS) score ≥2, steroid use at baseline and lactate dehydrogenase (LDH) level >240 IU/l were significantly associated with poor PFS (all p<0.05). Conclusion: PS score ≥2, steroid use at baseline and a high LDH level were predictive of poor PFS in patients with NSCLC treated with nivolumab. Careful monitoring is recommended for treating such patients with nivolumab (UMIN-ID: UMIN000025908).

http://ift.tt/2fMIpdk

A Proposal for Progression-Free Survival Assessment in Patients with Early Progressive Cancer

Background/Aim: Progression-free survival (PFS), which is evaluated in oncology clinical trials, is determined based on tumor progression evaluated according to an assessment schedule. There is possibly a bias in median PFS and hazard ratio (HR) for PFS depending on the assessment schedule referring to randomized controlled trials (RCTs) in patients with metastatic colorectal cancer. Materials and Methods: We re-analyzed the PFS in the FTD/TPI phase 2 trial by changing the assessment schedule. To assess biases in median PFS and HR for PFS resulting from different assessment schedules, we performed a computational simulation. Results: The reanalysis of FTD/TPI phase 2 trial and the simulation results showed that there were biases in median PFS and HR for PFS. Conclusion: In RCTs for early progressive cancer, median PFS is dependent on the assessment schedule; however, HR for PFS can be assessed without clinically-meaningful differences between assessment schedules, regardless of biomarker assumptions.

http://ift.tt/2yKOFtA

Study Identifies Crucial Characteristic of High-Risk HPV

By comparing the genomes of women infected with a high-risk type of human papillomavirus (HPV), researchers have found that a precise DNA sequence of a viral gene is associated with cervical cancer.

http://ift.tt/2gf0hOu

Study Identifies Crucial Characteristic of High-Risk HPV

By comparing the genomes of women infected with a high-risk type of human papillomavirus (HPV), researchers have found that a precise DNA sequence of a viral gene is associated with cervical cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2gf0hOu
via IFTTT

MiR-203a-3p suppresses cell proliferation and metastasis through inhibiting LASP1 in nasopharyngeal carcinoma

miR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported.

from Cancer via ola Kala on Inoreader http://ift.tt/2wzsntP
via IFTTT

Oncology Research Program

from Cancer via ola Kala on Inoreader http://ift.tt/2gflY0M
via IFTTT

NCCN News

from Cancer via ola Kala on Inoreader http://ift.tt/2ysv4Cc
via IFTTT

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non–muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

from Cancer via ola Kala on Inoreader http://ift.tt/2gfkmUQ
via IFTTT

Serving "a la CAR-T": Value-Based Pricing and Gene Therapy

from Cancer via ola Kala on Inoreader http://ift.tt/2yrGqX3
via IFTTT

Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50–64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.

from Cancer via ola Kala on Inoreader http://ift.tt/2gflW9a
via IFTTT

Implementation Framework for NCCN Guidelines

from Cancer via ola Kala on Inoreader http://ift.tt/2yrhyii
via IFTTT

Urothelial Carcinoma of the Bladder and the Rise of Immunotherapy

With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence. To date, pembrolizumab, a PD-1 inhibitor, has been granted full FDA approval based on its high antitumor activity, tolerability, and efficacy, with notable prolonged durable responses in the second-line setting. Nivolumab (a PD-1 inhibitor) and atezolizumab, durvalumab, and avelumab (PD-L1 inhibitors) have also gained accelerated drug approval in the second-line setting. In addition, atezolizumab and pembrolizumab have been approved for platinum-ineligible patients in the first-line setting. Effective 2-drug combinations reported include nivolumab plus the CTLA-4 antibody ipilimumab and pembrolizumab plus the IDO-1 inhibitor epacadostat. Further expansion of immunotherapy will hinge in part on the ability to define responders versus nonresponders through the use of biomarkers like PD-L1 or mutational load. Clinical trials with immunotherapy for metastatic disease as single agents or in combination are ongoing. This review explores the rise of immunotherapy and presents the current treatments and challenges posed with development of biomarkers, and provides a summary of ongoing phase III clinical trials.

from Cancer via ola Kala on Inoreader http://ift.tt/2gf0HVl
via IFTTT

To the Editor: Predictive Markers and Precision Medicine

from Cancer via ola Kala on Inoreader http://ift.tt/2yrG9U1
via IFTTT

Pathologic Complete Response After Neoadjuvant Chemotherapy and Long-Term Outcomes Among Young Women With Breast Cancer

Purpose: Breast cancer in young women is associated with an aggressive tumor biology and higher risk of recurrence. Pathologic complete response (pCR) after neoadjuvant therapy has been shown to be a surrogate marker for disease-free survival (DFS) and overall survival (OS), but the association between pCR and survival outcomes in young women with breast cancer is not well described. Methods: This study included women aged ≤40 years at diagnosis who received neoadjuvant chemotherapy (NAC) for stage II–III invasive breast cancer between 1998 and 2014 at Massachusetts General Hospital. Outcomes were compared between patients who achieved pCR (ypT0/is, ypN0) and those with residual disease. Results: A total of 170 young women were included in the analytical data set, of which 53 (31.2%) achieved pCR after NAC. The 5-year DFS rate for patients with and without pCR was 91% versus 60%, respectively (P<.01), and the OS rate was 95% versus 75%, respectively (P<.01). Among patients with pCR, no difference was seen in OS irrespective of baseline clinical stage (P=.6), but among patients with residual disease after NAC, a significant difference in OS based on baseline clinical stage was observed (P<.001). Conclusions: Our results suggest pCR after NAC is strongly associated with significantly improved DFS and OS in young women with breast cancer, and perhaps even more so than baseline stage. However, the significantly higher mortality for patients who did not attain pCR highlights the need for better therapies, and the neoadjuvant trial design could potentially serve as an efficient method for rapid triage and escalation/de-escalation of therapies to improve outcomes for young women with breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2z0fo65
via IFTTT

EGFR-Mutant Non-Small Cell Lung Cancer in the Era of Precision Medicine: Importance of Germline EGFR T790M Testing

With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying EGFR mutations and other molecular changes has become more crucial in the management of non–small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing EGFR mutations could be more useful than the histologic subtype itself. Germline T790M mutation should be suspected and tested for when multiple biopsies show de novo T790M mutations or when de novo T790M is found in patients with a family history of lung cancer. This case report presents a 60-year-old woman with bilateral NSCLC with 3 different distinct histologic diagnoses. Evaluating the molecular profile using NGS completely changed the diagnosis, prognosis, and management of this rare presentation of NSCLC.

from Cancer via ola Kala on Inoreader http://ift.tt/2y3mPvd
via IFTTT

A Population-Based Assessment of Emergency Department Observation Status for Older Adults With Cancer

Background: Hospitals' use of observation status for patients with cancer presenting to the emergency department (ED) is not well understood. This model of care delivery may be a viable alternative to inpatient admission for patients with cancer presenting with certain conditions. Our objective was to assess the use of observation status among Medicare beneficiaries with and without cancer. Methods: Population-based SEER-Medicare data were used to assess differences in the use of observation status between Medicare beneficiaries aged ≥66 years with and without cancer using a matched analysis (n=151,183 per cohort). We assessed the ratio of observation unit use to inpatient admission, between cancer and noncancer cohorts, and for patients diagnosed with breast, colon, lung, and prostate cancers. Poisson regression models were used to calculate observation rate estimates and 95% CIs while adjusting for selected patient characteristics. Results: When considering the volume of hospitalizations, observation status is used less frequently among beneficiaries with cancer than those without (43 vs 69 observation status visits per 1,000 inpatient admissions, respectively). The estimated observation rate per 1,000 inpatient admissions was higher for beneficiaries aged <75 years versus those aged ≥75 years, those with a Charlson comorbidity index of 0 vs 1 or ≥2, and those without a prior hospitalization versus those with ≥1 prior hospitalizations. Patients with breast and prostate cancers had higher adjusted and unadjusted observation rates per 1,000 inpatient admissions compared with those with colon and lung cancers. Conclusions: Observation status is used proportionately less for beneficiaries with cancer than those without. There may be opportunities to develop standards for ED staff to manage certain conditions for patients with cancer in observation status, and to reserve hospital resources for those who need it most.

from Cancer via ola Kala on Inoreader http://ift.tt/2z100Xr
via IFTTT

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018

Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET.

from Cancer via ola Kala on Inoreader http://ift.tt/2y4dfZa
via IFTTT

Clinical Significance of Histologic Variants of Bladder Cancer

Pathologists have identified many "histologic variants" of bladder cancer (BCA): histologic patterns that differ from conventional urothelial carcinoma (transitional cell carcinoma). Several of these are biologically aggressive, and their identification may aid in clinical decision-making. This article reviews several histologic variants and their value in deciding management of cT1 disease and predicting response to neoadjuvant chemotherapy (NAC). Diagnostic issues are also addressed, such as interobserver variability among pathologists. For example, although stage cT1 conventional urothelial carcinoma is usually managed conservatively, cT1 micropapillary carcinoma has high mortality following conservative management, and early cystectomy may reduce mortality. Similarly, plasmacytoid and small cell cancers are remarkably aggressive, and those diagnosed as stage cT1 at transurethral resection are likely understaged; conservative management thus greatly risks undertreatment. As an example of response, NAC dramatically reduces mortality in patients with small cell BCA, and is thus the standard of care, even in stage cT1 disease. Although identification of histologic variants may inform on optimal management, diagnostic issues challenge their incorporation into clinical practice. For example, interobserver reproducibility is only moderate for the diagnosis of micropapillary BCA. Studies have identified specific histologic issues underlying this diagnostic irreproducibility, and ongoing work aims to remedy this issue. In summary, histologic variants are emerging as potentially useful biomarkers in the management of BCA. Although issues remain unresolved, pathologists and treating physicians will benefit from understanding these variants and their prognostic and therapeutic implications.

from Cancer via ola Kala on Inoreader http://ift.tt/2z0fg6B
via IFTTT

The Senior Toronto Oncology Panel (STOP) Study: Research Participation for Older Adults With Cancer and Caregivers

Background: Patient engagement in research may lead to better-designed studies and improved health outcomes. The objectives of this study were to identify the research priorities of older adults with cancer (OAWCs) and their caregivers and examine how to engage these individuals in research teams and what supports are needed. Methods: We conducted 3 public meetings and 7 focus groups to delineate research priorities and the supports needed to facilitate integration of OAWCs and their caregivers on research teams. Results: A total of 33 older adults and 19 caregivers attended a public meeting and 27 older adults and 17 caregivers participated in a focus group. Most of the OAWCs and their caregivers had never participated in research before. Three themes were identified from the focus groups: (1) motivation to be on a team; (2) ability to make meaningful contributions; and (3) logistical considerations to facilitate engagement. Most participants were motivated to be a research team member and be involved in all steps of research if it could benefit them or future patients and caregivers. OAWCs and their caregivers were highly motivated to improve outcomes. Required logistics included flexibility regarding time and location, accessibility to computer technology, transportation support, materials worded in lay language, and attending/having short training sessions, as well as the presence of peer support. Conclusions: OAWCs and their caregivers are very motivated and willing to participate in research and to be research team members. Logistics and the social aspects of being on a team are important.

from Cancer via ola Kala on Inoreader http://ift.tt/2y3UrJt
via IFTTT

Admission or Observation? Population Health Is Here

from Cancer via ola Kala on Inoreader http://ift.tt/2z0f8E9
via IFTTT

Oncology Research Program

http://ift.tt/2gflY0M

NCCN News

http://ift.tt/2ysv4Cc

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non–muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

http://ift.tt/2gfkmUQ

Serving "a la CAR-T": Value-Based Pricing and Gene Therapy

http://ift.tt/2yrGqX3

Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50–64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.

http://ift.tt/2gflW9a

Implementation Framework for NCCN Guidelines

http://ift.tt/2yrhyii

Urothelial Carcinoma of the Bladder and the Rise of Immunotherapy

With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence. To date, pembrolizumab, a PD-1 inhibitor, has been granted full FDA approval based on its high antitumor activity, tolerability, and efficacy, with notable prolonged durable responses in the second-line setting. Nivolumab (a PD-1 inhibitor) and atezolizumab, durvalumab, and avelumab (PD-L1 inhibitors) have also gained accelerated drug approval in the second-line setting. In addition, atezolizumab and pembrolizumab have been approved for platinum-ineligible patients in the first-line setting. Effective 2-drug combinations reported include nivolumab plus the CTLA-4 antibody ipilimumab and pembrolizumab plus the IDO-1 inhibitor epacadostat. Further expansion of immunotherapy will hinge in part on the ability to define responders versus nonresponders through the use of biomarkers like PD-L1 or mutational load. Clinical trials with immunotherapy for metastatic disease as single agents or in combination are ongoing. This review explores the rise of immunotherapy and presents the current treatments and challenges posed with development of biomarkers, and provides a summary of ongoing phase III clinical trials.

http://ift.tt/2gf0HVl

To the Editor: Predictive Markers and Precision Medicine

http://ift.tt/2yrG9U1

Pathologic Complete Response After Neoadjuvant Chemotherapy and Long-Term Outcomes Among Young Women With Breast Cancer

Purpose: Breast cancer in young women is associated with an aggressive tumor biology and higher risk of recurrence. Pathologic complete response (pCR) after neoadjuvant therapy has been shown to be a surrogate marker for disease-free survival (DFS) and overall survival (OS), but the association between pCR and survival outcomes in young women with breast cancer is not well described. Methods: This study included women aged ≤40 years at diagnosis who received neoadjuvant chemotherapy (NAC) for stage II–III invasive breast cancer between 1998 and 2014 at Massachusetts General Hospital. Outcomes were compared between patients who achieved pCR (ypT0/is, ypN0) and those with residual disease. Results: A total of 170 young women were included in the analytical data set, of which 53 (31.2%) achieved pCR after NAC. The 5-year DFS rate for patients with and without pCR was 91% versus 60%, respectively (P<.01), and the OS rate was 95% versus 75%, respectively (P<.01). Among patients with pCR, no difference was seen in OS irrespective of baseline clinical stage (P=.6), but among patients with residual disease after NAC, a significant difference in OS based on baseline clinical stage was observed (P<.001). Conclusions: Our results suggest pCR after NAC is strongly associated with significantly improved DFS and OS in young women with breast cancer, and perhaps even more so than baseline stage. However, the significantly higher mortality for patients who did not attain pCR highlights the need for better therapies, and the neoadjuvant trial design could potentially serve as an efficient method for rapid triage and escalation/de-escalation of therapies to improve outcomes for young women with breast cancer.

http://ift.tt/2z0fo65

EGFR-Mutant Non-Small Cell Lung Cancer in the Era of Precision Medicine: Importance of Germline EGFR T790M Testing

With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying EGFR mutations and other molecular changes has become more crucial in the management of non–small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing EGFR mutations could be more useful than the histologic subtype itself. Germline T790M mutation should be suspected and tested for when multiple biopsies show de novo T790M mutations or when de novo T790M is found in patients with a family history of lung cancer. This case report presents a 60-year-old woman with bilateral NSCLC with 3 different distinct histologic diagnoses. Evaluating the molecular profile using NGS completely changed the diagnosis, prognosis, and management of this rare presentation of NSCLC.

http://ift.tt/2y3mPvd

A Population-Based Assessment of Emergency Department Observation Status for Older Adults With Cancer

Background: Hospitals' use of observation status for patients with cancer presenting to the emergency department (ED) is not well understood. This model of care delivery may be a viable alternative to inpatient admission for patients with cancer presenting with certain conditions. Our objective was to assess the use of observation status among Medicare beneficiaries with and without cancer. Methods: Population-based SEER-Medicare data were used to assess differences in the use of observation status between Medicare beneficiaries aged ≥66 years with and without cancer using a matched analysis (n=151,183 per cohort). We assessed the ratio of observation unit use to inpatient admission, between cancer and noncancer cohorts, and for patients diagnosed with breast, colon, lung, and prostate cancers. Poisson regression models were used to calculate observation rate estimates and 95% CIs while adjusting for selected patient characteristics. Results: When considering the volume of hospitalizations, observation status is used less frequently among beneficiaries with cancer than those without (43 vs 69 observation status visits per 1,000 inpatient admissions, respectively). The estimated observation rate per 1,000 inpatient admissions was higher for beneficiaries aged <75 years versus those aged ≥75 years, those with a Charlson comorbidity index of 0 vs 1 or ≥2, and those without a prior hospitalization versus those with ≥1 prior hospitalizations. Patients with breast and prostate cancers had higher adjusted and unadjusted observation rates per 1,000 inpatient admissions compared with those with colon and lung cancers. Conclusions: Observation status is used proportionately less for beneficiaries with cancer than those without. There may be opportunities to develop standards for ED staff to manage certain conditions for patients with cancer in observation status, and to reserve hospital resources for those who need it most.

http://ift.tt/2z100Xr

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018

Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET.

http://ift.tt/2y4dfZa

Clinical Significance of Histologic Variants of Bladder Cancer

Pathologists have identified many "histologic variants" of bladder cancer (BCA): histologic patterns that differ from conventional urothelial carcinoma (transitional cell carcinoma). Several of these are biologically aggressive, and their identification may aid in clinical decision-making. This article reviews several histologic variants and their value in deciding management of cT1 disease and predicting response to neoadjuvant chemotherapy (NAC). Diagnostic issues are also addressed, such as interobserver variability among pathologists. For example, although stage cT1 conventional urothelial carcinoma is usually managed conservatively, cT1 micropapillary carcinoma has high mortality following conservative management, and early cystectomy may reduce mortality. Similarly, plasmacytoid and small cell cancers are remarkably aggressive, and those diagnosed as stage cT1 at transurethral resection are likely understaged; conservative management thus greatly risks undertreatment. As an example of response, NAC dramatically reduces mortality in patients with small cell BCA, and is thus the standard of care, even in stage cT1 disease. Although identification of histologic variants may inform on optimal management, diagnostic issues challenge their incorporation into clinical practice. For example, interobserver reproducibility is only moderate for the diagnosis of micropapillary BCA. Studies have identified specific histologic issues underlying this diagnostic irreproducibility, and ongoing work aims to remedy this issue. In summary, histologic variants are emerging as potentially useful biomarkers in the management of BCA. Although issues remain unresolved, pathologists and treating physicians will benefit from understanding these variants and their prognostic and therapeutic implications.

http://ift.tt/2z0fg6B

The Senior Toronto Oncology Panel (STOP) Study: Research Participation for Older Adults With Cancer and Caregivers

Background: Patient engagement in research may lead to better-designed studies and improved health outcomes. The objectives of this study were to identify the research priorities of older adults with cancer (OAWCs) and their caregivers and examine how to engage these individuals in research teams and what supports are needed. Methods: We conducted 3 public meetings and 7 focus groups to delineate research priorities and the supports needed to facilitate integration of OAWCs and their caregivers on research teams. Results: A total of 33 older adults and 19 caregivers attended a public meeting and 27 older adults and 17 caregivers participated in a focus group. Most of the OAWCs and their caregivers had never participated in research before. Three themes were identified from the focus groups: (1) motivation to be on a team; (2) ability to make meaningful contributions; and (3) logistical considerations to facilitate engagement. Most participants were motivated to be a research team member and be involved in all steps of research if it could benefit them or future patients and caregivers. OAWCs and their caregivers were highly motivated to improve outcomes. Required logistics included flexibility regarding time and location, accessibility to computer technology, transportation support, materials worded in lay language, and attending/having short training sessions, as well as the presence of peer support. Conclusions: OAWCs and their caregivers are very motivated and willing to participate in research and to be research team members. Logistics and the social aspects of being on a team are important.

http://ift.tt/2y3UrJt

Admission or Observation? Population Health Is Here

http://ift.tt/2z0f8E9

Erratum to: How to choose the best journal for your case report

http://ift.tt/2krvgv8

Development, Validation, and Dissemination of a Breast Cancer Recurrence Detection and Timing Informatics Algorithm

Abstract

Background

This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims and electronic health records data.

Methods

The algorithm has two parts: to detect the presence of recurrence and to estimate the timing of recurrence. The primary data source was the Cancer Research Network Virtual Data Warehouse (VDW). Sixteen potential indicators of recurrence were considered for model development. The final recurrence detection and timing models were determined, respectively, by maximizing the area under the ROC curve (AUROC) and minimizing average absolute error. Detection and timing algorithms were validated using VDW data in comparison with a gold standard recurrence capture from a third site in which recurrences were validated through chart review. Performance of this algorithm, stratified by stage at diagnosis, was compared with other published algorithms. All statistical tests were two-sided.

Results

Detection model AUROCs were 0.939 (95% confidence interval [CI] = 0.917 to 0.955) in the training data set (n = 3370) and 0.956 (95% CI = 0.944 to 0.971) and 0.900 (95% CI = 0.872 to 0.928), respectively, in the two validation data sets (n = 3370 and 3961, respectively). Timing models yielded average absolute prediction errors of 12.6% (95% CI = 10.5% to 14.5%) in the training data and 11.7% (95% CI = 9.9% to 13.5%) and 10.8% (95% CI = 9.6% to 12.2%) in the validation data sets, respectively, and were statistically significantly lower by 12.6% (95% CI = 8.8% to 16.5%, P < .001) than those estimated using previously reported timing algorithms. Similar covariates were included in both detection and timing algorithms but differed substantially from previous studies.

Conclusions

Valid and reliable detection of recurrence using data derived from electronic medical records and insurance claims is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for breast cancer patients and those who develop recurrence.

http://ift.tt/2fNbXaJ

Tumor localization may change the type of adjuvant treatment in gastric cancer

http://ift.tt/2xYsLUB

Reply to Tumor localization may change the type of adjuvant treatment in gastric cancer

http://ift.tt/2y3Iwvx

Development, Validation, and Dissemination of a Breast Cancer Recurrence Detection and Timing Informatics Algorithm

Abstract

Background

This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims and electronic health records data.

Methods

The algorithm has two parts: to detect the presence of recurrence and to estimate the timing of recurrence. The primary data source was the Cancer Research Network Virtual Data Warehouse (VDW). Sixteen potential indicators of recurrence were considered for model development. The final recurrence detection and timing models were determined, respectively, by maximizing the area under the ROC curve (AUROC) and minimizing average absolute error. Detection and timing algorithms were validated using VDW data in comparison with a gold standard recurrence capture from a third site in which recurrences were validated through chart review. Performance of this algorithm, stratified by stage at diagnosis, was compared with other published algorithms. All statistical tests were two-sided.

Results

Detection model AUROCs were 0.939 (95% confidence interval [CI] = 0.917 to 0.955) in the training data set (n = 3370) and 0.956 (95% CI = 0.944 to 0.971) and 0.900 (95% CI = 0.872 to 0.928), respectively, in the two validation data sets (n = 3370 and 3961, respectively). Timing models yielded average absolute prediction errors of 12.6% (95% CI = 10.5% to 14.5%) in the training data and 11.7% (95% CI = 9.9% to 13.5%) and 10.8% (95% CI = 9.6% to 12.2%) in the validation data sets, respectively, and were statistically significantly lower by 12.6% (95% CI = 8.8% to 16.5%, P < .001) than those estimated using previously reported timing algorithms. Similar covariates were included in both detection and timing algorithms but differed substantially from previous studies.

Conclusions

Valid and reliable detection of recurrence using data derived from electronic medical records and insurance claims is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for breast cancer patients and those who develop recurrence.

from Cancer via ola Kala on Inoreader http://ift.tt/2fNbXaJ
via IFTTT

Tumor localization may change the type of adjuvant treatment in gastric cancer

from Cancer via ola Kala on Inoreader http://ift.tt/2xYsLUB
via IFTTT

Reply to Tumor localization may change the type of adjuvant treatment in gastric cancer

from Cancer via ola Kala on Inoreader http://ift.tt/2y3Iwvx
via IFTTT

miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment

Abstract

Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore, it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently, extracellular vesicles—particularly exosomes—have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner. Previous studies have shown inconsistent results regarding miR-200c-3p expression levels in OSCC cell lines, tissues, or serum—likely because of the heterogeneous characters of the specimen materials. For this reason, single-cell clone analyses are necessary to effectively assess the role of exosome-derived miRNAs on cells within the tumor microenvironment. The present study utilized integrated microarray profiling to compare exosome-derived miRNA and exosome-treated cell-derived mRNA expression. Data were acquired from noninvasive SQUU-A and highly invasive SQUU-B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa-miR-200c-3p was a key pro-invasion factor among six miRNA candidates. Consistently, silencing of the miR-200c-3p targets, CHD9 and WRN, significantly accelerated the invasive potential of SQUU-A cells. Thus, our data indicate that miR-200c-3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non-invasive counterparts. This article is protected by copyright. All rights reserved

from Cancer via ola Kala on Inoreader http://ift.tt/2z0By8o
via IFTTT

miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment

Abstract

Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore, it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently, extracellular vesicles—particularly exosomes—have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner. Previous studies have shown inconsistent results regarding miR-200c-3p expression levels in OSCC cell lines, tissues, or serum—likely because of the heterogeneous characters of the specimen materials. For this reason, single-cell clone analyses are necessary to effectively assess the role of exosome-derived miRNAs on cells within the tumor microenvironment. The present study utilized integrated microarray profiling to compare exosome-derived miRNA and exosome-treated cell-derived mRNA expression. Data were acquired from noninvasive SQUU-A and highly invasive SQUU-B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa-miR-200c-3p was a key pro-invasion factor among six miRNA candidates. Consistently, silencing of the miR-200c-3p targets, CHD9 and WRN, significantly accelerated the invasive potential of SQUU-A cells. Thus, our data indicate that miR-200c-3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non-invasive counterparts. This article is protected by copyright. All rights reserved

http://ift.tt/2z0By8o

Biography—Hidenori Inohara

http://ift.tt/2xzLuqU

Preface

http://ift.tt/2f8YUzX

Biography—Hidenori Inohara

from Cancer via ola Kala on Inoreader http://ift.tt/2xzLuqU
via IFTTT

Preface

from Cancer via ola Kala on Inoreader http://ift.tt/2f8YUzX
via IFTTT

Spontaneous Remission of Severe Systemic Langerhans Cell Histiocytosis with Bladder Involvement: A Case Study

Background: The clinical presentation of Langerhans cell histiocytosis (LCH) is heterogeneous ranging from single-organ involvement to systemic disease causing substantial morbidity and mortality. We describe an unusual course of severe multisystem LCH with spontaneous remission. Case Presentation: We report on a 45-year-old Caucasian woman with cervical cancer, FIGO stage IVB. Five months after the end of combined radiochemotherapy and brachytherapy, the patient was readmitted because of severe dysuria. Sterile leukocyturia was seen, and cystoscopy revealed only 3 unspecific small mucosal lesions compatible with postradiation cystitis. Incidentally, a computed tomography (CT) scan of the body showed diffuse micronodular and cystic lesions in lungs and hypodense lesions in the liver. Biopsies revealed infiltrations of CD1a and Langerin (CD207)-positive histiocytes in the lung, liver, and bladder. Additionally, positron emission tomography-CT (PET-CT) was compatible with bone involvement. Retrospective analysis revealed that the increase in alkaline phosphatase might have been a surrogate of bone marrow infiltration with osseous activity. Repeated pneumothoraces occurred, and only one course of vinblastine-prednisolone could be applied. Despite ongoing tobacco consumption and without further therapy, PET-CT showed considerable remission 2 months later. However, despite stable remission, documented by serial PET and conventional CT scans, persistent infiltration of the bladder by Langerhans histiocytes could still be demonstrated 17 months later. Unfortunately, cervical cancer recurred and progressed. Conclusion: Multisystem LCH may rapidly occur, may be oligosymptomatic and, even in high-risk cases, remission without specific therapy might occur. Whether alkaline phosphatase might be a surrogate to monitor osseous disease activity has to be further explored.
Case Rep Oncol 2017;10:876–884

http://ift.tt/2fTCTsP

Transplant-Ineligible Symptomatic but Indolent Multiple Myeloma Shows Better Prognosis with Conventional Agents

The survival of multiple myeloma patients has improved significantly over the last several decades. However, the median overall survival of these patients remains less than 5 years. In this report, we discuss 4 cases of multiple myeloma patients that showed long survival. Interestingly, these patients had severe organ damage at diagnosis, used only conventional agents, and did not always show deep response. Although current guidelines recommend novel agents to achieve deep response, the current cases suggest that some multiple myeloma patients may not need intensive treatment. Here, we discuss 4 cases of symptomatic but indolent transplant-ineligible myeloma.
Case Rep Oncol 2017;10:871–875

http://ift.tt/2xkc098

Consequences of introducing geometric GTV to CTV margin expansion in DAHANCA contouring guidelines for head and neck radiotherapy

Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs.

http://ift.tt/2xk9M4U

Treating locally advanced lung cancer with a 1.5T MR-Linac – Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy

This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients.

http://ift.tt/2wA4ylW

Different manifestation of irradiation induced coronary artery disease detected with coronary computed tomography compared with matched non-irradiated controls

Patients who received chest irradiation for treatment of a malignancy are at increased risk for the development of coronary artery atherosclerosis. Little is known about the anatomical coronary artery plaque characteristics of irradiation induced coronary artery disease (CAD). This study aimed to evaluate potential differences in the presence, extent, severity, composition and location of CAD in patients treated with mediastinal irradiation compared with non-irradiated controls matched on age, gender and cardiovascular risk factors.

http://ift.tt/2xkh5cH

Consensus Contouring Guidelines for Post-Operative Completely Resected Cavity Stereotactic Radiosurgery (SRS) for Brain Metastases

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hany Soliman, Mark Ruschin, Lilyana Angelov, Paul D. Brown, Veronica L.S. Chiang, John P. Kirkpatrick, Simon S. Lo, Anita Mahajan, Kevin S. Oh, Jason P. Sheehan, Scott G. Soltys, Arjun Sahgal
PurposeCavity stereotactic radiosurgery (SRS) is an emerging treatment option after surgical resection of brain metastases. No guidelines for contouring the surgical cavity volume have been reported. The aim of this study was to propose contouring guidelines based on consensus contours generated by 10 international experts.MethodsTen post-operative completely resected cases with varying clinical scenarios and locations within the brain were selected. For each case, 10 experts independently contoured the surgical cavity clinical target volume (CTV). All the contours were analyzed and agreement was calculated using the Simultaneous Truth and Performance Level Estimation (STAPLE) with the kappa statistic. A follow-up survey was also completed by each investigator in order to summarize their contouring rationale based on a number of different clinical scenarios. Both the results from the survey and consensus STAPLE contours were summarized to establish contouring guidelines.ResultsThere was a high level of agreement between the expert CTV contours (mean sensitivity=0.75, mean specificity=0.98), and the mean kappa was 0.65. The agreement was statistically significant at p<0.001 for all cases. Based on these results and analyses of the survey answers, recommendations for CTV include: fusion of the pre-operative MRI to aid in volume delineation, contouring the entire surgical tract regardless of the preoperative location of the tumor, the CTV should be extended 5-10mm along the dura overlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact, and a margin of up to 5mm into the adjacent sinus is sufficient when there is pre-operative venous sinus contact.ConclusionsConsensus contouring guidelines for post-operative completely resected cavity SRS treatment were established based on expert contours and clinical practice. However, in the absence of clinical data supporting the recommendations in this paper, these guidelines serve as a baseline for further study and refinement.



http://ift.tt/2y29Jya

Efficient interplay effect mitigation for proton pencil beam scanning by spot-adapted layered repainting evenly spread out over the full breathing cycle

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Per Rugaard Poulsen, John Eley, Ulrich Langner, Charles B. Simone, Katja Langen
PurposeTo develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS).MethodsA new flexible repainting scheme with spot-adapted numbers of repaintings evenly spread out over the whole breathing cycle (here assumed to be 4s) was developed. Twelve fields from five thoracic and upper abdominal PBS plans were delivered three times with the new repainting scheme to an ion chamber array on a motion stage: once static and twice with 4s,3cm peak-to-peak sinusoidal motion with delivery started at maximum inhale and maximum exhale. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3mm gamma pass rate was calculated using the motion-convolved static dose as reference. Simulations were first validated with the experiments and then used to extend the study to 0-5cm motion magnitude, 2-6s motion periods, patient-measured liver tumor motion, and 1-6 fraction treatments. The effect of the proposed method was evaluated for the five clinical cases by 4D dose reconstruction in the planning 4DCT scan. The target homogeneity index, HI=(D2-D98)/Dmean, of a single fraction delivery was reported.ResultsThe gamma pass rates were 59.6±9.7% (no repainting), 76.5±10.8% (8 repaintings), and 92.4±3.8% (new repainting scheme). Simulations reproduced the experimental gamma pass rates with 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had similar gamma pass rates as 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the five test cases was 14.2% (no repainting), 13.7% (8 repaintings), 12.0% (new repainting scheme), and 11.6% (4D dose without interplay effects).ConclusionsA novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations and dose reconstructions. This strategy may allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments.



http://ift.tt/2gcgLqG

Efficient interplay effect mitigation for proton pencil beam scanning by spot-adapted layered repainting evenly spread out over the full breathing cycle

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Per Rugaard Poulsen, John Eley, Ulrich Langner, Charles B. Simone, Katja Langen
PurposeTo develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS).MethodsA new flexible repainting scheme with spot-adapted numbers of repaintings evenly spread out over the whole breathing cycle (here assumed to be 4s) was developed. Twelve fields from five thoracic and upper abdominal PBS plans were delivered three times with the new repainting scheme to an ion chamber array on a motion stage: once static and twice with 4s,3cm peak-to-peak sinusoidal motion with delivery started at maximum inhale and maximum exhale. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3mm gamma pass rate was calculated using the motion-convolved static dose as reference. Simulations were first validated with the experiments and then used to extend the study to 0-5cm motion magnitude, 2-6s motion periods, patient-measured liver tumor motion, and 1-6 fraction treatments. The effect of the proposed method was evaluated for the five clinical cases by 4D dose reconstruction in the planning 4DCT scan. The target homogeneity index, HI=(D2-D98)/Dmean, of a single fraction delivery was reported.ResultsThe gamma pass rates were 59.6±9.7% (no repainting), 76.5±10.8% (8 repaintings), and 92.4±3.8% (new repainting scheme). Simulations reproduced the experimental gamma pass rates with 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had similar gamma pass rates as 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the five test cases was 14.2% (no repainting), 13.7% (8 repaintings), 12.0% (new repainting scheme), and 11.6% (4D dose without interplay effects).ConclusionsA novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations and dose reconstructions. This strategy may allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments.



from Cancer via ola Kala on Inoreader http://ift.tt/2gcgLqG
via IFTTT

Consensus Contouring Guidelines for Post-Operative Completely Resected Cavity Stereotactic Radiosurgery (SRS) for Brain Metastases

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hany Soliman, Mark Ruschin, Lilyana Angelov, Paul D. Brown, Veronica L.S. Chiang, John P. Kirkpatrick, Simon S. Lo, Anita Mahajan, Kevin S. Oh, Jason P. Sheehan, Scott G. Soltys, Arjun Sahgal
PurposeCavity stereotactic radiosurgery (SRS) is an emerging treatment option after surgical resection of brain metastases. No guidelines for contouring the surgical cavity volume have been reported. The aim of this study was to propose contouring guidelines based on consensus contours generated by 10 international experts.MethodsTen post-operative completely resected cases with varying clinical scenarios and locations within the brain were selected. For each case, 10 experts independently contoured the surgical cavity clinical target volume (CTV). All the contours were analyzed and agreement was calculated using the Simultaneous Truth and Performance Level Estimation (STAPLE) with the kappa statistic. A follow-up survey was also completed by each investigator in order to summarize their contouring rationale based on a number of different clinical scenarios. Both the results from the survey and consensus STAPLE contours were summarized to establish contouring guidelines.ResultsThere was a high level of agreement between the expert CTV contours (mean sensitivity=0.75, mean specificity=0.98), and the mean kappa was 0.65. The agreement was statistically significant at p<0.001 for all cases. Based on these results and analyses of the survey answers, recommendations for CTV include: fusion of the pre-operative MRI to aid in volume delineation, contouring the entire surgical tract regardless of the preoperative location of the tumor, the CTV should be extended 5-10mm along the dura overlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact, and a margin of up to 5mm into the adjacent sinus is sufficient when there is pre-operative venous sinus contact.ConclusionsConsensus contouring guidelines for post-operative completely resected cavity SRS treatment were established based on expert contours and clinical practice. However, in the absence of clinical data supporting the recommendations in this paper, these guidelines serve as a baseline for further study and refinement.



from Cancer via ola Kala on Inoreader http://ift.tt/2y29Jya
via IFTTT