Cancer by Sfakianakis Alexandros: 04/09/18

Δευτέρα 9 Απριλίου 2018

Why Aren't There More Female Pain Medicine Physicians?

Despite a growing awareness about the importance of gender equity and the rising number of women in medicine, women remain persistently underrepresented in pain medicine and anesthesiology. Pain medicine ranks among the bottom quartile of medical specialties in terms of female applicants, female trainees, and proportion of female practitioners. Female pain medicine physicians are also notably disadvantaged compared with their male colleagues in most objective metrics of gender equity, which include financial compensation, career advancement, public recognition, and leadership positions. Increased gender diversity among pain medicine physicians is vital to fostering excellence in pain research, education, and clinical care, as well as creating a high-quality work environment. Pain medicine stands at a crossroads as a specialty, and must examine reasons for its current gender gap and consider a call to action to address this important issue. Accepted for publication December 24, 2017. Address correspondence to: Tina L. Doshi, MD, Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, 550 N Broadway, Suite 309C, Baltimore, MD 21205 (e-mail: tina.doshi@jhmi.edu). The authors have no sources of funding to declare for this article. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

https://ift.tt/2GPCbJC

Clinicopathological significance of tumor-infiltrating lymphocytes and programmed death-1 expression in cutaneous melanoma: a comparative study on clinical subtypes

Interactions between immune cells and tumor cells play an important role in tumor progression. We evaluated patterns of tumor-infiltrating lymphocytes (TILs) and programmed death-1 (PD-1) expression in acral and nonacral cutaneous melanoma, and determined their effects on clinicopathological characteristics and biologic responses. We identified 122 cases of cutaneous melanoma, of which 39 were cases of non-nail unit acral melanoma (NNUAM), 35 were cases of nail unit melanoma (NUM), and 48 were cases of nonacral melanoma. Clinicopathological features and survival outcomes were analyzed according to the scores for TILs and PD-1 expression in intratumoral and peritumoral compartments. The effects of the presence of TILs and PD-1 expression on various clinicopathological factors differed according to the clinical subtypes of cutaneous melanoma. The frequency of intratumoral TILs and PD-1 expression were lower in NUM than in the other two subtypes. The density of peritumoral PD-1 was significantly higher in NNUAM. In NUM and nonacral melanoma, a low density of intratumoral TILs and PD-1 was associated with a deeper Breslow thickness and the presence of a vertical growth phase. In NNUAM, a high density of peritumoral TILs and PD-1 was associated with a shallower Breslow thickness and less frequent extracutaneous dissemination. In NNUAM, a high density of peritumoral PD-1 was associated with a better prognosis. This study suggests that the effects of PD-1+ TILs on biological activity differ according to the clinical subtypes of cutaneous melanoma. Correspondence to Mi W. Lee, MD, PhD, Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 Gil, Songpa-gu, Seoul 05505, Korea Tel: +82 230 103 460; fax: +82 248 67831; e-mail: miumiu@amc.seoul.kr Received December 8, 2017 Accepted March 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2HcJ6fk

Immune privilege: failure of immunotherapy in controlling metastatic cutaneous melanoma to the eye

This report concerns a 49-year-old female with cutaneous malignant melanoma and systemic metastases. These resolved following combination immunotherapy with ipilimumab and nivolumab. She subsequently experienced unilateral floaters, an increase in iris pigmentation and pigmentary glaucoma. The eye progressively lost vision and became painful due to iris neovascularization. The clinical diagnosis was of cutaneous melanoma metastatic to the vitreous, ciliary body and iris. Enucleation was performed for symptom control, with histopathology confirming the clinical diagnosis. The immune privilege of the eye may preclude ocular metastasis control with immunotherapy. Ocular symptoms in such patients merit referral to an ophthalmologist. Correspondence to David I.T. Sia, MBChB, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK Tel: +44 77 2980 2148; fax: +44 20 7566 2972; e-mail: david.sia@me.com Received November 21, 2017 Accepted February 15, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2GLNxdn

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18 F-FDG and 18 F-FLT PET/CT imaging

Abstract

Background

Despite the significant upgrading in recent years of the role of ¹⁸F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3′-Deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate ¹⁸F-FLT PET/CT in imaging of MM patients, in the context of its combined use with ¹⁸F-FDG PET/CT.

Results

Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent ¹⁸F-FDG PET/CT and ¹⁸F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. ¹⁸F-FDG PET/CT demonstrated focal, ¹⁸F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, ¹⁸F-FLT PET/CT showed focal, ¹⁸F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 ¹⁸F-FDG avid, focal, MM-indicative lesions were detected with ¹⁸F-FDG PET/CT, while 17 ¹⁸F-FLT avid, focal, MM-indicative lesions were detected with ¹⁸F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for ¹⁸F-FDG PET/CT than for ¹⁸F-FLT PET/CT. A common finding was a mismatch of focally increased ¹⁸F-FDG uptake and reduced ¹⁸F-FLT uptake (lower than the surrounding bone marrow). Moreover, ¹⁸F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUV_mean and SUV_max were significantly higher for ¹⁸F-FLT than for ¹⁸F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers.

Conclusions

Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that ¹⁸F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

from Cancer via ola Kala on Inoreader https://ift.tt/2qgPcRg
via IFTTT

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18 F-FDG and 18 F-FLT PET/CT imaging

Abstract

Background

Results

Conclusions

https://ift.tt/2qgPcRg

Why does chemotherapy stop affecting the cells of ovarian and breast tumors?

Future Oncology, Ahead of Print.

from Cancer via ola Kala on Inoreader https://ift.tt/2IGgsAb
via IFTTT

The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients

Future Oncology, Ahead of Print.

from Cancer via ola Kala on Inoreader https://ift.tt/2HdOa3b
via IFTTT

Why does chemotherapy stop affecting the cells of ovarian and breast tumors?

Future Oncology, Ahead of Print.

https://ift.tt/2IGgsAb

The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients

Future Oncology, Ahead of Print.

https://ift.tt/2HdOa3b

Use of lymphoscintigraphy to differentiate primary versus secondary lower extremity lymphedema after surgical lymphadenectomy: a retrospective analysis

Abstract

Background

When managing patients with cancer, lymphedema of the lower limbs (LLL) is commonly reported as secondary to the surgical excision and/or irradiation of lymph nodes (LNs). In the framework of lymphoscintigraphic imaging performed to evaluate secondary LLL, some lympho-nodal presentations have been observed that could not be explained by the applied treatments, suggesting that these LLL might be primary. Therefore, all our lymphoscintigraphic examinations that were performed in patients for LLL after surgery for gynecological or urological cancer were retrospectively analyzed in order to evaluate the frequency in which these LLL might not be secondary (either completely or partially) but primary in origin.

Methods

Lymphoscintigraphies performed in 33 patients who underwent LN dissection (limited to the intra-abdominal LN) with or without radiotherapy for histologically confirmed ovarian cancer (n = 6), uterine cancer (n = 14 with cervical cancer and n = 7 with endometrial cancer), or prostate cancer (n = 6) were compared to lymphoscintigraphies obtained in primary LLL.

Results

In 12 (33% of the) patients (3 men plus 9 women, 4 with cervical cancer and 5 with endometrial cancer), scintigraphy of the lower limbs revealed lympho-nodal presentation that did not match with the expected consequences of the surgical and/or radiological treatments and were either suggestive or typical of primary lymphedema.

Conclusions

This retrospective analysis of a limited but well-defined series of patients suggests that the appearance of LLL might not be related to cancer treatment(s) but that these LLL may represent the development of a primary lymphatic disease latent prior to the therapeutic interventions.

https://ift.tt/2GKJguU

Use of lymphoscintigraphy to differentiate primary versus secondary lower extremity lymphedema after surgical lymphadenectomy: a retrospective analysis

Abstract

Background

Methods

Results

Conclusions

from Cancer via ola Kala on Inoreader https://ift.tt/2GKJguU
via IFTTT

Identification and validation of a 3-gene methylation classifier for HPV-based cervical screening on self-samples

Purpose: Offering self-sampling of cervico-vaginal material for high-risk human papillomavirus (hrHPV) testing is an effective method to increase the coverage in cervical screening programs. Molecular triage directly on hrHPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a DNA methylation classifier for detection of cervical precancer (CIN3) and cancer, applicable to lavage and brush self-samples. Experimental Design: We determined genome-wide DNA methylation profiles of 72 hrHPV-positive self-samples, using the Infinium Methylation 450K Array. The selected DNA methylation markers were evaluated by multiplex quantitative methylation-specific PCR (qMSP) in both hrHPV-positive lavage (n=245) and brush (n=246) self-samples from screening cohorts. Subsequently, logistic regression analysis was performed to build a DNA methylation classifier for CIN3 detection applicable to self-samples of both devices. For validation, an independent set of hrHPV-positive lavage (n=199) and brush (n=287) self-samples was analyzed. Results: Genome-wide DNA methylation profiling revealed 12 DNA methylation markers for CIN3 detection. Multiplex qMSP analysis of these markers in large series of lavage and brush self-samples yielded a 3-gene methylation classifier (ASCL1, LHX8 and ST6GALNAC5). This classifier showed a very good clinical performance for CIN3 detection in both lavage (AUC=0.88; sensitivity=74%; specificity=79%) and brush (AUC=0.90; sensitivity=88%; specificity=81%) self-samples in the validation set. Importantly, all self-samples from women with cervical cancer scored DNA methylation-positive. Conclusion: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on hrHPV-positive self-samples, which is superior to currently available methods.

from Cancer via ola Kala on Inoreader https://ift.tt/2qjVnEd
via IFTTT

Complete and durable responses in Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab and Dexamethasone

Purpose: Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a complication of solid organ transplantation with a poor prognosis and typically associated with Epstein-Barr virus (EBV). We hypothesized EBV lytic-phase protein expression would allow successful treatment with antiviral therapy. Experimental Design: Thirteen patients were treated with zidovudine (AZT), ganciclovir (GCV), dexamethasone, and rituximab in EBV+ PCNS-PTLD. Twice-daily, intravenous AZT 1500 mg, GCV 5 mg/kg, and dexamethasone 10 mg were given for 14-days. Weekly Rituximab 375 mg/m2 was delivered for the first four weeks. Twice-daily Valganciclovir 450 mg and AZT 300 mg started day 15. Lytic and latent protein expression was assessed using in situ hybridization and immunohistochemistry. Immunoblot assay assessed lytic gene activation. Cells transfected with lytic kinase vectors were assessed for sensitivity to our therapy using MTS tetrazolium and flow cytometry. Results: The median time to response was 2 months. Median therapy duration was 26.5 months. Median follow-up was 52 months. The estimated two-year overall survival (OS) was 76.9% (95% CI: 44.2-91.9%). Overall response rate (ORR) was 92% (95% CI: 64-100%). BXLF1/vTK and BGLF4 expression was found in the seven tumor biopsies evaluated. Lytic gene expression was induced in vitro using the four-drug regimen. Transfection with viral kinase cDNA increased cellular sensitivity to antiviral therapy. Conclusions: EBV+ PCNS-PTLD expressed lytic kinases and therapy with AZT, GCV, rituximab and dexamethasone provided durable responses. Induction of the lytic protein expression and increased cellular sensitivity to antiviral therapy after transfection with viral kinase cDNA provides a mechanistic rationale for our approach.

from Cancer via ola Kala on Inoreader https://ift.tt/2GMTkDC
via IFTTT

Identification and validation of a 3-gene methylation classifier for HPV-based cervical screening on self-samples

https://ift.tt/2qjVnEd

Complete and durable responses in Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab and Dexamethasone

https://ift.tt/2GMTkDC

More Rules, Still Exceptions: Understanding Immunomodulatory Antibody Activity In Vivo

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Andrea Ipsen-Escobedo, Falk Nimmerjahn
Understanding how agonistic and checkpoint control antibodies mediate their activity in vivo is essential for further development of these promising anti-cancer therapies. In this issue of Cancer Cell, studies by Vargas et al. and Yu et al. provide insights into the mode of action of CTLA-4- and CD40-specific antibodies.

Teaser

Understanding how agonistic and checkpoint control antibodies mediate their activity in vivo is essential for further development of these promising anti-cancer therapies. In this issue of Cancer Cell, studies by Vargas et al. and Yu et al. provide insights into the mode of action of CTLA-4- and CD40-specific antibodies.

https://ift.tt/2Hbd96W

T Cell Dysfunction in Cancer

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Daniela S. Thommen, Ton N. Schumacher
Therapeutic reinvigoration of tumor-specific T cells has greatly improved clinical outcome in cancer. Nevertheless, many patients still do not achieve durable benefit. Recent evidence from studies in murine and human cancer suggest that intratumoral T cells display a broad spectrum of (dys-)functional states, shaped by the multifaceted suppressive signals that occur within the tumor microenvironment. Here we discuss the current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how our emerging understanding of T cell dysfunction may be utilized to develop personalized strategies to restore antitumor immunity.

Teaser

Therapeutic reinvigoration of tumor-specific T cells has greatly improved clinical outcome in cancer. Nevertheless, many patients still do not achieve durable benefit. Recent evidence from studies in murine and human cancer suggest that intratumoral T cells display a broad spectrum of (dys-)functional states, shaped by the multifaceted suppressive signals that occur within the tumor microenvironment. Here we discuss the current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how our emerging understanding of T cell dysfunction may be utilized to develop personalized strategies to restore antitumor immunity.

https://ift.tt/2GOaQ6z

The Immune Revolution: A Case for Priming, Not Checkpoint

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Robert H. Vonderheide
Most tumors are unresponsive to immune checkpoint blockade, especially if deep immunosuppression in the tumor develops prior to and prevents T cell immunosurveillance. Failed or frustrated T cell priming often needs repair before successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical role in generating T cell immunity, by activating dendritic cells, and converting cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate T cell-dependent anti-tumor activity, especially in combination with chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With the advent of multiple CD40 agonists with acceptable single-agent toxicity, clinical evaluation of CD40 combinations has accelerated.

Teaser

Most tumors are unresponsive to immune checkpoint blockade, especially if deep immunosuppression in the tumor develops prior to and prevents T cell immunosurveillance. Failed or frustrated T cell priming often needs repair before successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical role in generating T cell immunity, by activating dendritic cells, and converting cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate T cell-dependent anti-tumor activity, especially in combination with chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With the advent of multiple CD40 agonists with acceptable single-agent toxicity, clinical evaluation of CD40 combinations has accelerated.

https://ift.tt/2HcnlMG

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Vancheswaran Gopalakrishnan, Beth A. Helmink, Christine N. Spencer, Alexandre Reuben, Jennifer A. Wargo
The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.

Teaser

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.

https://ift.tt/2GOaL2L

Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Roberta Zappasodi, Taha Merghoub, Jedd D. Wolchok
Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from "self," generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.

Teaser

Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from "self," generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.

https://ift.tt/2HcngZo

Mechanistic Insights into Transmissible Cancers of Mammals

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Susan Bullman, Tao Zou, Matthew Meyerson
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. In this issue of Cancer Cell, two articles by Stammnitz et al. and Frampton et al. present novel insights into the potential mechanisms underlying the propagation of naturally occurring transmissible cancers in mammals.

Teaser

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. In this issue of Cancer Cell, two articles by Stammnitz et al. and Frampton et al. present novel insights into the potential mechanisms underlying the propagation of naturally occurring transmissible cancers in mammals.

https://ift.tt/2IGDPK9

Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Stephen J. Russell, Glen N. Barber
Selective destruction of neoplastic tissues by oncolytic viruses (OVs) leads to antigen-agnostic boosting of neoantigen-specific cytotoxic T lymphocyte (CTL) responses, making OVs ideal companions for checkpoint blockade therapy. Here we discuss the mechanisms whereby OVs modulate both adjuvanticity and antigenicity of tumor cells. Suppression of antitumor immunity after OV therapy has not been observed, possibly because viral antigen expression diminishes as the antiviral response matures, thereby progressively honing the CTL response to tumor neoantigens. By combining direct in situ tumor destruction with the ability to boost antitumor immunity, OVs also have the potential to be powerful standalone cancer therapies.

https://ift.tt/2HcncJ8

The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Maximilian R. Stammnitz, Tim H.H. Coorens, Kevin C. Gori, Dane Hayes, Beiyuan Fu, Jinhong Wang, Daniel E. Martin-Herranz, Ludmil B. Alexandrov, Adrian Baez-Ortega, Syd Barthorpe, Alexandra Beck, Francesca Giordano, Graeme W. Knowles, Young Mi Kwon, George Hall, Stacey Price, Ruth J. Pye, Jose M.C. Tubio, Hannah V.T. Siddle, Sukhwinder Singh Sohal, Gregory M. Woods, Ultan McDermott, Fengtang Yang, Mathew J. Garnett, Zemin Ning, Elizabeth P. Murchison
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation.

Graphical abstract

Teaser

Stammnitz et al. show that the two transmissible cancer clones that affect Tasmanian devils are very similar in their tissues-of-origin, mutational patterns and driver gene candidates. Importantly, these cancers are both highly sensitive to inhibitors of some receptor tyrosine kinases as well as to inhibitors of DNA repair.

https://ift.tt/2GLicaJ

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Dan Frampton, Hagen Schwenzer, Gabriele Marino, Lee M. Butcher, Gabriele Pollara, Janos Kriston-Vizi, Cristina Venturini, Rachel Austin, Karina Ferreira de Castro, Robin Ketteler, Benjamin Chain, Richard A. Goldstein, Robin A. Weiss, Stephan Beck, Ariberto Fassati
The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression.

Graphical abstract

Teaser

By analyzing serial biopsies of vincristine-treated canine transmissible venereal tumors, Frampton et al. show that tumor regression occurs in sequential steps involving the activation of the innate immune system and immune infiltration of the tumor, and they identify CCL5 as a possible driver of regression.

https://ift.tt/2Hcn64e

Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Kyohei Nakamura, Sahar Kassem, Alice Cleynen, Marie-Lorraine Chrétien, Camille Guillerey, Eva Maria Putz, Tobias Bald, Irmgard Förster, Slavica Vuckovic, Geoffrey R. Hill, Seth L. Masters, Marta Chesi, P. Leif Bergsagel, Hervé Avet-Loiseau, Ludovic Martinet, Mark J. Smyth
Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk^∗MYC MM progression in a CD8⁺ T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses. Strikingly, high levels of bone marrow plasma IL-18 were associated with poor overall survival in MM patients. Furthermore, our preclinical studies suggested that IL-18 could be a potential therapeutic target in MM.

Graphical abstract

Teaser

Nakamura et al. show that IL-18 produced by the multiple myeloma (MM) niche promotes MM progression in a CD8⁺ T cell-dependent manner in a mouse model and that IL-18 could be a potential therapeutic target in MM. High levels of bone marrow plasma IL-18 are associated with poor overall survival in MM patients.

https://ift.tt/2IGDFT3

Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Jianfeng Huang, Angeles Duran, Miguel Reina-Campos, Tania Valencia, Elias A. Castilla, Timo D. Müller, Matthias H. Tschöp, Jorge Moscat, Maria T. Diaz-Meco
Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion, which mediates tumor fatty acid oxidation and invasion, leading to aggressive metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a general shutdown of energy-utilizing pathways through mTORC1 inhibition, which supports nutrient availability for cancer cells. This reveals a central role of adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables cancer metabolic fitness.

Graphical abstract

Teaser

Huang et al. show in a prostate cancer mouse model that p62 loss in adipocytes leads to aggressive disease by increasing osteopontin secretion, which mediates tumor fatty acid oxidation and invasion. P62 deficiency also represses energy-consuming pathways in adipocytes, increasing nutrient availability for tumors.

https://ift.tt/2Hcn0JU

Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Yong Yu, Kolja Schleich, Bin Yue, Sujuan Ji, Philipp Lohneis, Kristel Kemper, Mark R. Silvis, Nouar Qutob, Ellen van Rooijen, Melanie Werner-Klein, Lianjie Li, Dhriti Dhawan, Svenja Meierjohann, Maurice Reimann, Abdel Elkahloun, Steffi Treitschke, Bernd Dörken, Christian Speck, Frédérick A. Mallette, Leonard I. Zon, Sheri L. Holmen, Daniel S. Peeper, Yardena Samuels, Clemens A. Schmitt, Soyoung Lee

https://ift.tt/2IHQZGJ

Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases Therapeutic Efficacy in Myeloproliferative Neoplasms

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Maria Kleppe, Richard Koche, Lihua Zou, Peter van Galen, Corinne E. Hill, Lauren Dong, Sofie De Groote, Efthymia Papalexi, Amritha V. Hanasoge Somasundara, Keith Cordner, Matthew Keller, Noushin Farnoud, Juan Medina, Erin McGovern, Jaime Reyes, Justin Roberts, Matthew Witkin, Franck Rapaport, Julie Teruya-Feldstein, Jun Qi, Raajit Rampal, Bradley E. Bernstein, James E. Bradner, Ross L. Levine

https://ift.tt/2HcmX0G

Mechanistic Insights into Transmissible Cancers of Mammals

Teaser

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy

Teaser

More Rules, Still Exceptions: Understanding Immunomodulatory Antibody Activity In Vivo

Teaser

T Cell Dysfunction in Cancer

Teaser

The Immune Revolution: A Case for Priming, Not Checkpoint

Teaser

Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies

Teaser

Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines

The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

Graphical abstract

Teaser

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Graphical abstract

Teaser

Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment

Graphical abstract

Teaser

Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor

Graphical abstract

Teaser

Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases Therapeutic Efficacy in Myeloproliferative Neoplasms

Hiding in Plain Sight: Rediscovering the Importance of Noncoding RNA in Human Malignancy

At the time of its construction in the 1950s, the central dogma of molecular biology was a useful model that represented the current state of knowledge for the flow of genetic information after a period of prolific scientific discovery. Unknowingly, it also biased many of our assumptions going forward. Whether intentional or not, genomic elements not fitting into this paradigm were deemed unimportant and emphasis on the study of protein-coding genes prevailed for decades. The phrase "Junk DNA," first popularized in the 1960s, is still used with alarming frequency to describe the entirety of noncoding DNA. It has since become apparent that RNA molecules not coding for protein are vitally important in both normal development and human malignancy. Cancer researchers have been pioneers in determining noncoding RNA function and developing new technologies to study these molecules. In this review, we will discuss well known and newly emerging species of noncoding RNAs, their functions in cancer, and new technologies being utilized to understand their mechanisms of action in cancer. Cancer Res; 1–10. ©2018 AACR.

https://ift.tt/2qjWPGy

Hiding in Plain Sight: Rediscovering the Importance of Noncoding RNA in Human Malignancy

NCCN Conference Addressed Value-Based Healthcare Models, Payer Perspectives, New NCCN Guidelines, and Other Updates in Cancer Care

from Cancer via ola Kala on Inoreader https://ift.tt/2Ey09mD
via IFTTT

Oncology Research Program

from Cancer via ola Kala on Inoreader https://ift.tt/2JAcevo
via IFTTT

Medical Care Costs Associated With Cancer in Integrated Delivery Systems

Background: The high economic burden of cancer is projected to continue growing. Cost-of-care estimates are key inputs for comparative effectiveness and economic analyses that aim to inform policies associated with cancer care. Existing estimates are based largely on SEER-Medicare data in the elderly, leaving a knowledge gap regarding costs for patients aged <65 years. Methods: We estimated total and net medical care costs using data on individuals diagnosed with breast, colorectal, lung, or prostate cancer (n=45,522) and noncancer controls (n=314,887) enrolled in 1 of 4 participating health plans. Net costs were defined as the difference in mean total costs between patients with cancer and controls. The phase-of-care approach and Kaplan-Meier Sample Average method were used to estimate mean total and net 1- and 5-year costs (in 2015 US dollars) by cancer site, stage at diagnosis, and age group (<65 and ≥65 years). Results: Total and net costs were consistently highest for lung cancer and lowest for prostate cancer. Net costs were higher across all cancer sites for patients aged <65 years than those aged ≥65 years. Medical care costs for all cancers increased with advanced stage at diagnosis. Conclusions: This study improves understanding of medical care costs for the 4 most common invasive cancers in the United States. Higher costs among patients aged <65 years highlight limitations of relying on SEER-Medicare data alone to understand the national burden of cancer, whereas higher costs for patients with advanced-stage cancer underscore the importance of early detection to curtail high long-term costs. These cost estimates can be used in the development and evaluation of interventions and policies across the cancer care continuum.

from Cancer via ola Kala on Inoreader https://ift.tt/2IEdH2f
via IFTTT

Standing Together or Alone

from Cancer via ola Kala on Inoreader https://ift.tt/2JwIzDb
via IFTTT

Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor–positive SBE contingent on AET use for the initial DCIS diagnosis.

from Cancer via ola Kala on Inoreader https://ift.tt/2IEdyfd
via IFTTT

Letter to the Editor: Panax Ginseng for Cancer-Related Fatigue

from Cancer via ola Kala on Inoreader https://ift.tt/2JyGJ4E
via IFTTT

NCCN Guidelines as a Model of Extended Criteria for Lung Cancer Screening

Background: This review assessed the performance of patients in NCCN high-risk group 2 in a clinical CT lung screening (CTLS) program. Methods: We retrospectively reviewed screening results for all patients from our institution undergoing clinical CTLS from January 2012 through December 2016, with follow-up through June 2017. To qualify for screening, patients had to meet the NCCN Guidelines high-risk criteria for CTLS, have a physician order for screening, be asymptomatic, be lung cancer–free for 5 years, and have no known metastatic disease. We compared demographics and screening performance of NCCN high-risk groups 1 and 2 across >4 rounds of screening. Screening metrics assessed included rates of positive and suspicious examinations, significant incidental and infectious/inflammatory findings, false negatives, and cancer detection. We also compared cancer stage and histology detected in each NCCN high-risk group. Results: A total of 2,927 individuals underwent baseline screening, of which 698 (24%) were in NCCN group 2. On average, group 2 patients were younger (60.6 vs 63.1 years), smoked less (38.8 vs 50.8 pack-years), had quit longer (18.1 vs 6.3 years), and were more often former smokers (61.4% vs 44.2%). Positive and suspicious examination rates, false negatives, and rates of infectious/inflammatory findings were equivalent in groups 1 and 2 across all rounds of screening. An increased rate of cancer detection was observed in group 2 during the second annual (T2) screening round (2.7% vs 0.5%; P=.005), with no difference in the other screening rounds: baseline (T0; 2% vs 2.3%; P=.61), first annual (T1; 1.2% vs 1.7%; P=.41), and third annual and beyond (≥T3; 1.2% vs 1.1%; P=1.00). Conclusions: CTLS appears to be equally effective in both NCCN high-risk groups.

from Cancer via ola Kala on Inoreader https://ift.tt/2ExVxNh
via IFTTT

Concurrent BRAF/MEK Inhibitors in BRAF V600-Mutant High-Grade Primary Brain Tumors

BRAF V600 mutations are being identified in patients with primary brain tumors more often as molecular testing becomes widely available. Targeted treatment with BRAF inhibitors has been attempted in individual cases with some responses, whereas others showed no response or developed resistance. Preclinical work suggests that gliomas could be more responsive to the concurrent use of BRAF and MEK inhibition for MAP kinase pathway suppression. This report presents 2 cases of malignant brain tumors with BRAF V600E mutations that were resistant to radiation and temozolomide, and reports on their response to targeted treatment with the BRAF and MEK inhibitors dabrafenib and trametinib. One patient with an anaplastic pleomorphic xanthoastrocytoma experienced a partial response for 14 months, demonstrated by progressive tumor shrinkage and clinical improvement; however, this was followed by clinical and radiographic progression. The patient with glioblastoma continued to have stable disease after 16 months of treatment. These cases are encouraging in a disease that urgently needs new treatments. Further work is necessary to understand response rates, duration, and survival in primary brain tumors.

from Cancer via ola Kala on Inoreader https://ift.tt/2JAbJBw
via IFTTT

Single-Arm Longitudinal Study to Evaluate a Decision Aid for Women Offered Neoadjuvant Systemic Therapy for Operable Breast Cancer

Background: Neoadjuvant systemic therapy (NAST) is an increasingly used treatment option for women with large operable or highly proliferative breast cancer. With equivalent survival outcomes between NAST and up-front surgery, the situation-specific preference-sensitive nature of the decision makes it suitable for a decision aid (DA). This study aimed to develop and evaluate a DA for this population. Methods: A DA booklet was developed according to international standards, including information about adjuvant and neoadjuvant treatment, outcome probabilities, and a values clarification exercise. Eligible women, considered by investigators as candidates for NAST, were enrolled in a multi-institutional, single-arm, longitudinal study. Patient-reported outcome measure questionnaires were completed pre- and post-DA, between chemotherapy and surgery, and at 12 months. Outcomes were feasibility (percentage of eligible patients accessing the DA); acceptability to patients (percentage who would recommend it to others) and clinicians (percentage who would use the DA in routine practice); and decision-related outcomes. Results: From 77 eligible women, 59 were enrolled, of whom 47 (79.7%; 95% CI, 69.4–89.9) reported having read the DA; 51 completed the first post-DA questionnaire. Of these 51, 41 participants (80.4%; 95% CI, 69.5–91.3) found the DA useful for their decision about NAST. Of 18 responding investigators, 16 (88.9%; 95% CI, 74.4–103.4) indicated they would continue to use the DA in routine practice. Post-DA, decisional conflict decreased significantly (P<.01); anxiety and distress decreased significantly; and 86.3% (95% CI, 73.7–94.3) achieved at least as much decisional control as they desired. Conclusions: This DA was feasible and acceptable to patients and clinicians, and improvement in decision-related outcomes was demonstrated when used in combination with clinical consultations. This DA could safely be implemented into routine practice for women considering NAST for operable breast cancer.

from Cancer via ola Kala on Inoreader https://ift.tt/2IHkV5P
via IFTTT

Biallelic TSC2 Mutations in a Patient With Chromophobe Renal Cell Carcinoma Showing Extraordinary Response to Temsirolimus

mTOR inhibitors are used to treat renal cell carcinoma (RCC). Treatment response is variable and appears to correlate with genetic alterations that activate mTOR signaling. Recently, everolimus was suggested to be more effective than sunitinib in chromophobe RCC (chRCC), a tumor with frequent mTOR pathway defects. This report presents the genomic and functional characterization of a metastatic chRCC that showed complete response at metastatic sites and 80% reduction in primary tumor size upon temsirolimus treatment. After surgery, the patient remained disease-free for 8 years after temsirolimus therapy. Whole-exome sequencing (WES) revealed 2 somatic variants in TSC2, a critical negative regulator of mTOR: a splicing defect (c.5069-1G>C) and a novel missense variant [c.3200_3201delinsAA; p.(V1067E)]. In vitro functional assessment demonstrated that the V1067E substitution disrupted TSC2 function. Immunohistochemistry in the tumor tissues revealed increased phosphorylated S6 ribosomal protein, indicating mTOR pathway activation. In conclusion, WES revealed TSC2 inactivation as the likely mechanism for this extraordinary response to temsirolimus. These findings support high efficacy of mTOR inhibitors in a subset of patients with chRCC and propose sequencing of mTOR pathway genes to help guide therapy.

from Cancer via ola Kala on Inoreader https://ift.tt/2JAbyWS
via IFTTT

High Variability in Lymph Node Counts Among an International Cohort of Pathologists: Questioning the Scientific Validity of Node Counts

Background: The enumeration of lymph nodes (LNs) from surgical specimens plays a critical role in the staging of patients with cancer. LN count (LNC) can affect prognosis, staging, adequacy of resection, and/or eligibility for clinical trials. However, there is no standard method for counting LNs. Most studies in the literature site the pathology report as the source of LN data, without discussion of the counting criteria. Patients and Methods: Four microscopic slides from separate pelvic LN dissections were digitally scanned and uploaded with their gross descriptions to an online library and an online survey. Respondents were asked how many LNs they would count per slide as part of a staging procedure. The survey was distributed to an international cohort of pathologists. Results: A total of 122 surveys were returned: 79 from practicing pathologists and 43 from residents/fellows. There was no statistical difference between the groups. All slides showed significant individual variability. The LNC range for each slide was as follows: slide 1, 1–3; slide 2, 0–13; slide 3, 1–8; slide 4, 1–11. The intraclass correlation (ICC) for all responders was 0.26 (95% CI, 0.05<ICC<0.74), which demonstrates a very low agreement among individuals. Although there is a small amount of literature assessing causes of variability in counts, nearly all focus on different techniques at the grossing bench. Our study is the largest prospective assessment of LNC by an international cohort of pathologists. We have demonstrated tremendous variation in the number of LNs pathologists report for a given slide, thus significantly altering how many total LNs are counted. This calls into question the clinical utility of node counts, as well as their use as a quality indicator. Conclusions: LNC is subject to tremendous interpathologist variation, which has a significant clinical and research impact. Consensus in pathologic handling and microscopic enumeration of LNs is essential.

from Cancer via ola Kala on Inoreader https://ift.tt/2IFhYTi
via IFTTT

NCCN Guidelines Insights: Colon Cancer, Version 2.2018

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation–positive metastatic colorectal cancer with regimens containing vemurafenib.

from Cancer via ola Kala on Inoreader https://ift.tt/2JwcVWm
via IFTTT

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

from Cancer via ola Kala on Inoreader https://ift.tt/2IGvKoq
via IFTTT

Trends in Incidence and Factors Affecting Survival of Patients With Cholangiocarcinoma in the United States

Background: Cholangiocarcinoma (CCA) includes cancers arising from the intrahepatic and extrahepatic bile ducts. The etiology and pathogenesis of CCA remain poorly understood. This is the first study investigating both incidence patterns of CCA from 1973 through 2012 and demographic, clinical, and treatment variables affecting survival of patients with CCA. Patients and Methods: Using the SEER database, age-adjusted incidence rates were evaluated from 1973–2012 using SEER*Stat software. A retrospective cohort of 26,994 patients diagnosed with CCA from 1973–2008 was identified for survival analysis. Cox proportional hazards models were used to perform multivariate survival analysis. Results: Overall incidence of CCA increased by 65% from 1973–2012. Extrahepatic CCA (ECC) remained more common than intrahepatic CCA (ICC), whereas the incidence rates for ICC increased by 350% compared with a 20% increase seen with ECC. Men belonging to non–African American and non-Caucasian ethnicities had the highest incidence rates of CCA. This trend persisted throughout the study period, although African Americans and Caucasians saw 50% and 59% increases in incidence rates, respectively, compared with a 9% increase among other races. Median overall survival (OS) was 8 months in patients with ECC compared with 4 months in those with ICC. Our survival analysis found Hispanic women to have the best 5-year survival outcome (P<.0001). OS diminished with age (P<.0001), and ECC had better survival outcomes compared with ICC (P<.0001). Patients who were married, were nonsmokers, belonged to a higher income class, and underwent surgery had better survival outcomes compared with others (P<.0001). Conclusions: This is the most up-to-date study of CCA from the SEER registry that shows temporal patterns of increasing incidence of CCA across different races, sexes, and ethnicities. We identified age, sex, race, marital status, income, smoking status, anatomic location of CCA, tumor grade, tumor stage, radiation, and surgery as independent prognostic factors for OS in patients with CCA.

from Cancer via ola Kala on Inoreader https://ift.tt/2JuVzt0
via IFTTT

BRAF-Targeted Therapy in the Treatment of BRAF-Mutant High-Grade Gliomas in Adults

from Cancer via ola Kala on Inoreader https://ift.tt/2IFhWe8
via IFTTT

NCCN Conference Addressed Value-Based Healthcare Models, Payer Perspectives, New NCCN Guidelines, and Other Updates in Cancer Care

https://ift.tt/2Ey09mD

Oncology Research Program

https://ift.tt/2JAcevo

Medical Care Costs Associated With Cancer in Integrated Delivery Systems

https://ift.tt/2IEdH2f

Standing Together or Alone

https://ift.tt/2JwIzDb

Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ

https://ift.tt/2IEdyfd

Letter to the Editor: Panax Ginseng for Cancer-Related Fatigue

https://ift.tt/2JyGJ4E

NCCN Guidelines as a Model of Extended Criteria for Lung Cancer Screening

https://ift.tt/2ExVxNh

Concurrent BRAF/MEK Inhibitors in BRAF V600-Mutant High-Grade Primary Brain Tumors

https://ift.tt/2JAbJBw

Single-Arm Longitudinal Study to Evaluate a Decision Aid for Women Offered Neoadjuvant Systemic Therapy for Operable Breast Cancer

https://ift.tt/2IHkV5P

Biallelic TSC2 Mutations in a Patient With Chromophobe Renal Cell Carcinoma Showing Extraordinary Response to Temsirolimus

https://ift.tt/2JAbyWS

High Variability in Lymph Node Counts Among an International Cohort of Pathologists: Questioning the Scientific Validity of Node Counts

https://ift.tt/2IFhYTi

NCCN Guidelines Insights: Colon Cancer, Version 2.2018

https://ift.tt/2JwcVWm

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology

https://ift.tt/2IGvKoq

Trends in Incidence and Factors Affecting Survival of Patients With Cholangiocarcinoma in the United States

https://ift.tt/2JuVzt0

BRAF-Targeted Therapy in the Treatment of BRAF-Mutant High-Grade Gliomas in Adults

https://ift.tt/2IFhWe8

Stereotactic ablative radiotherapy after concomitant chemoradiotherapy in non-small cell lung cancer: A TITE-CRM phase 1 trial

Platinum based chemoradiotherapy is the standard of care for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can have a dose dependent response with stereotactic ablative radiotherapy (SABR), we hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy could increase treatment efficacy. The purpose of this study was to determine feasibility of such an approach.

https://ift.tt/2Exm3Xj

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma

Abstract

Background

Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus.

Methods

We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae).

Results

The frequency of LNM to the middle mediastinal and supraclavicular zones, including the Mt and Ce, respectively, was lower than to the upper and lower mediastinal and abdominal zone in patients with superficial and advanced thoracic ESCC. In cadavers, the lymphatic vessel counts of the intra-outer longitudinal muscle layer in the Mt and Ce were significantly lower than those of the Lt and Ae, suggesting that lymphatic flow toward the outside of the Mt and Ce was not more abundant than to other sites.

Conclusion

Our anatomical data suggested that the absence of intra-muscle lymphatic vessels in the middle mediastinal and supraclavicular zones causes skip LNM in patients with thoracic ESCC. Thus, standard esophagectomy with lymph node dissection, including distant zones, may be appropriate for treating patients with superficial thoracic ESCC.

https://ift.tt/2EyAcTM

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience

Abstract

Background

The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA).

Methods

A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC.

Results

Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1–100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1–33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1–100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1–100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS.

Conclusion

The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

https://ift.tt/2Jy3PZs