Tabaco y cáncer. Informe del Cirujano General 2014

El Informe 2014 del Cirujano General de los EEUU es muy impactante. Fumar aumenta el riesgo de muerte de los pacientes con cáncer, aumenta el riesgo de un segundo cáncer y también hay una fuerte evidencia que empeora los efectos adversos de los tratamientos.

Helping Cancer Patients Quit Smoking Should Be a Standard of Care
Graham W. Warren, MD, PhD and K. Michael Cummings, PhD, MPH
Published Online: Monday, March 30, 2015

Overwhelming evidence presented in the 2014 Surgeon General’s Report resulted in the conclusion that smoking causes adverse outcomes in patients with cancer.1 Current smoking increases risk for overall mortality by a median of 51% and increases the risk of cancer-specific mortality by a median of 61%. Smoking further increases the risk of developing a second primary cancer and has strong associations with an increased risk of toxicity from cancer treatment. One or more adverse effects of smoking are noted across virtually all cancer disease sites and for all treatment modalities including surgery, radiotherapy, and systemic therapy.

Yet despite these data, most oncologists do not regularly provide evidence-based tobacco cessation support for patients with cancer who smoke.2 Some of the reasons that oncologists do not offer this support include not feeling confident in their ability to assist their patients in stopping smoking, a lack of time, and a lack of available resources.3

However, addressing tobacco use by patients with cancer is not as difficult as some might think. Established evidence-based guidelines are available4 and online resources have been developed specifically for use by clinical oncologists.5 Recent reviews have discussed methods to improve cessation support for patients with cancer that basically rely upon asking patients about tobacco use, advising patients to quit smoking, and assisting patients in quitting smoking using principles of behavioral counseling and pharmacotherapy.6,7 Physicians and other clinical providers can directly assist patients with cessation support or can refer patients to resources such as dedicated institutional tobacco cessation programs, state help line services, or specialized counselors who can be integrated into a busy oncology clinic.

Recognizing the merits of such efforts, leading cancer organizations such as the American Society of Clinical Oncology, the American Association for Cancer Research, and the International Association for the Study of Lung Cancer have advocated for providing cessation support to all patients with cancer who use tobacco.8-10

Graham W. Warren, MD, PhD
Associate Professor

Vice Chairman for Research

Department of Radiation Oncology

Hollings Cancer Center
Medical University of South Carolina
Charleston, SC

Vacuna autóloga en Cáncer de Ovario

Autologous Vaccine Delays Progression Following Surgery for Ovarian Cancer
Darcy Lewis
Published Online: Monday, March 30, 2015
Jonathan Oh, MD

Treatment with the immunotherapy Vigil, formally known as FANG, delayed time to progression in all patients with stage III/IV ovarian cancer who were treated with the autologous tumor cell vaccine compared with those who were not, according to an open-label phase II trial.

In the 31-patient trial, which was presented at the 2015 SGO Annual Meeting, patients were randomized to receive the vaccine or no treatment following surgery. Of the 20 patients who received the vaccine, a median time to progression had not yet been reached compared with a median of 14.5 months in those who were not treated.

Additionally, the Vigil vaccine, composed of granulocyte macrophage colony-stimulating factor [GM-CSF] bi-shRNAi furin vector-transfected autologous tumor cells, demonstrated an acceptable safety profile, and participants showed a high rate of immune response via T-cell activation.

Lead author Jonathan Oh, MD, of Texas Oncology in Dallas, called the study findings encouraging. “Results in phase II ovarian cancer suggest Vigil-mediated prolongation of time to recurrence,” he said during a scientific plenary session.

A preceding trial discovered longer-than-expected survival duration that correlated with ELISPOT reactivity. This earlier trial examined a variety of advanced tumors, ranging from adenoid cystic carcinoma to synovial sarcoma. Ovarian cancers represented a small percentage of the study total.

“We believe further randomized assessment is justified based on a 93% ELISPOT [Enzyme-Linked ImmunoSPOT assay] conversion in phase II to minimal residual disease in ovarian cancer. That’s compared to a phase I result of 54% conversion in patients with bulky disease.”

Oh et al narrowed the phase II study’s focus to ovarian cancer for several reasons. “Approximately 75% of stage III/IV patients with ovarian cancer who achieve clinical complete response (cCR) relapse within 2 years, and there is no standard of care for maintenance therapy,” he noted. “We thought there was potential to determine regression-free survival (RFS) difference by running a 2:1 randomized phase II trial.”

Study participants were patients with stage III/IV ovarian cancer who achieved cCR following surgical debulking and chemotherapy. Tumor tissue was harvested during surgical debulking to use in vaccine construction. Once patients achieved cCR and were confirmed to be ELISPOT-negative, 20 patients were randomized to receive the Vigil treatment, and 11 patients were randomized to the non-Vigil group.

Patients in the active treatment group received 1.0 x 107 cells/intradermal injection once monthly for up to 12 doses. Patients in the control group received no maintenance therapy. The trial design allowed for patients to be transferred to the active treatment group if they experienced disease progression during the trial.

Adverse events (AEs) were minimal. During phase I, phase II, and phase II crossover combined, 50 patients with ovarian cancer received a total of 141 Vigil injections. No grade 3 or 4 AEs were recorded in the phase II study. Only one grade 2 AE was reported (erythema). The most common grade 1 AEs were indurations (28), injection-site reactions (14), and erythema (23).

The phase II trial’s key endpoints were patient safety, immune response, and RFS. Noting that the historical average of RFS is 13 to 18 months, the team discontinued this trial when the active treatment group’s median RFS reached 19.3 months compared with 12.4 months in the control group.

With the 3-year disease-recurrence rate of 60% in the active treatment group compared with 91% in the control group, researchers will pursue a phase III trial involving 382 evaluable patients.

“It’s especially important to note that approximately 93% of patients demonstrated T-cell activation against their tumor antigen as early as 1 month after vaccination,” Oh said. “This is an area of great potential.”

In February 2015, a phase III study was initiated to explore Vigil as a treatment for women with stages III/IV high-grade ovarian cancer following cytoreduction and 5 to 6 cycles of standard of care chemotherapy. The company developing the vaccine, Gradalis, plans to submit findings from this study to regulatory authorities, if they are positive.

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Empaquetamiento genérico: gran éxito del gobierno Australiano.

En 2012 el gobierno australiano obligó por ley al empaquetamiento genérico del tabaco. Es decir, todos los paquetes son similares independientemente de la compañía que lo produce y ademas, tienen advertencias más grandes. Según los epidemiólogos esto ha sido un éxito. No creo que ningún gobierno español, sea cual fuere, se atreva a una medida así.

RESEARCH REPORT
You have free access to this content
Personal tobacco pack display before and after the introduction of plain packaging with larger pictorial health warnings in Australia: an observational study of outdoor café strips
1. Meghan Zacher1,
2. Megan Bayly1,
3. Emily Brennan2,
4. Joanne Dono3,
5. Caroline Miller3,
6. Sarah Durkin1,
7. Michelle Scollo1 and
8. Melanie Wakefield1,*
Article first published online: 25 FEB 2014
DOI: 10.1111/add.12466
© 2014 Society for the Study of Addiction
Issue

Addiction
Volume 109, Issue 4, pages 653–662, April 2014

Abstract
Aims
We tested whether prevalence of cigarette pack display and smoking at outdoor venues and pack orientation changed following the introduction of plain packaging and larger pictorial health warnings in Australia.
Methods
Between October and April 2011–12 (pre-plain packaging, pre-PP) and 2012–13 (post-plain packaging, post-PP), we counted patrons, smokers and tobacco packs at cafés, restaurants and bars with outdoor seating. Pack type (fully branded, plain or unknown) and orientation were noted. Rates of pack display, smoking and pack orientation were analysed using multi-level Poisson regression.
Results
Pack display declined by 15% [adjusted incident rate ratio (IRR) = 0.85, 95% confidence interval (CI) = 0.79–0.91, P < 0.001], driven by a 23% decline in active smoking (IRR = 0.77, 95% CI = 0.71–0.84, P  < 0.001) between phases. The decline in pack display coincided with the full implementation of plain packaging from December 2012, was stronger in venues with children present and was limited to mid and high socio-economic status (SES) areas. The proportion of packs orientated face-up declined from 85.4% of fully branded packs pre-PP to 73.6% of plain packs post-PP (IRR = 0.87, 95% CI = 0.79–0.95, P =  0.002). Alternatively, the proportions concealed by telephones, wallets or other items (4.4% of fully branded packs pre-PP and 9.5% of plain packs post-PP; IRR = 2.33, 95% CI = 1.72–3.17, P < 0.001) and in an external case (1.5–3.5% of all packs; IRR = 2.79, 95% CI = 1.77–4.40, P  < 0.001) increased. Low SES areas evidenced the greatest increase in pack concealment and the greatest decline in face-up pack orientation. Conclusions
Following Australia's 2012 policy of plain packaging and larger pictorial health warnings on cigarette and tobacco packs, smoking in outdoor areas of cafés, restaurants and bars and personal pack display (packs clearly visible on tables) declined. Further, a small proportion of smokers took steps to conceal packs that would otherwise be visible. Both are promising outcomes to minimize exposure to tobacco promotion.

Células Dendríticas e inmunoterapia del cáncer

La historia de nuestro conocimiento del sistema inmune es fascinante. La células dendríticas, verdaderas estrellas de este sistmea, están en el centro de la inmunoterapia del cáncer. Este artículo hace un buen resumen de ello.

Review
Nature Reviews Cancer 12, 265-277 (April 2012) | doi:10.1038/nrc3258
FOCUS ON: Tumour immunology & immunotherapy
Cancer immunotherapy via dendritic cells
Karolina Palucka1,2 & Jacques Banchereau3 About the authors
Summary

• The molecular identification of human cancer antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Cancer vaccines aim to induce tumour-specific effector T cells that can reduce the tumour mass and to induce tumour-specific memory T cells that can control tumour relapse.

• Owing to their properties, dendritic cells (DCs) are often called 'nature's adjuvants' and thus have become the natural targets for antigen delivery. DCs provide an essential link between the innate and the adaptive immune responses. DCs are at the centre of the immune system owing to their ability to control both tolerance and immune responses. These key properties of DCs render them the central candidates for antigen delivery and vaccination, including therapeutic vaccination against cancer.

• The immune system has the potential to eliminate neoplastic cells. However, tumour cells alone are poor antigen-presenting cells (APCs). Studies with mouse models demonstrate that the generation of protective anti-tumour immune responses depends on the presentation of tumour antigens by DCs. When compared with other APCs, such as macrophages, DCs are extremely efficient at antigen presentation and inducing T cell immunity, thus explaining their nickname of 'professional APCs'.

• Mice and humans have distinct functional subsets of DCs that generate different types of immune response. DCs are also able to mature; that is, to acquire novel functions following microbe encounters. Under steady state conditions, DCs in peripheral tissues are 'immature'. These immature DCs induce tolerance either through T cell deletion or through inducing the expansion of regulatory and/or suppressor T cells. DCs promptly respond to environmental signals and differentiate into mature DCs that can efficiently launch immune responses. It is now accepted that the adjuvant component of vaccines primarily acts by triggering DC maturation.

• DCs are important targets for therapeutic interventions in cancer. Two themes of research are growing: first, how cancer cells alter DC physiology; and second, how we can build on the powerful properties of DCs to generate novel cancer immunotherapies (including vaccines).
Top of page
Author affiliations
1. Baylor Institute for Immunology Research, 3434 Live Oak Avenue, Dallas, Texas 75204, USA.
2. Department of Oncological Sciences, Immunology Institute, Mount Sinai School of Medicine, New York 10029-6574, New York, USA.
3. Pharma Research and Early Development, Hoffmann-La Roche, Nutley, New Jersey 07110, USA.
Correspondence to: Karolina Palucka1,2 Email: KarolinP@Baylorhealth.edu

Inmunología y cáncer

Immunity
Volume 39, Issue 1, 25 July 2013, Pages 1–10

Review
Oncology Meets Immunology: The Cancer-Immunity Cycle
• Daniel S. Chen1, 3,
• Ira Mellman2, 3, ,

doi:10.1016/j.immuni.2013.07.012
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Under an Elsevier user license
Open Archive
________________________________________
The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer.
________________________________________
Main Text
Introduction
The development of cancer immunotherapy has reached an important inflection point in the history of cancer therapy (reviewed in Mellman et al., 2011). Durable monotherapy responses are consistently being reported for a broad range of human cancers with several different agents (Hamid et al., 2013a, Herbst et al., 2013, Hodi et al., 2010 and Topalian et al., 2012b), providing a compelling argument that cancer immunotherapy is active in a range of indications beyond melanoma, a disease often thought to be atypically immunogenic (Jacobs et al., 2012). In addition to encouraging activity, many of the cancer immunotherapy approaches report safety profiles that are milder and more manageable than traditional or targeted (i.e., oncogene-centric) cancer therapies.
Cancer is characterized by the accumulation of a variable number of genetic alterations and the loss of normal cellular regulatory processes (Tian et al., 2011). These events have long been known to result in the expression of neoantigens, differentiation antigens, or cancer testis antigens, which can lead to presentation of peptides bound to major histocompatibility class I (MHCI) molecules on the surface of cancer cells, distinguishing them from their normal counterparts. Since the work of Boon and colleagues, we have known that these cancer-specific peptide-MHCI complexes can be recognized by CD8+ T cells produced spontaneously in cancer patients (Boon et al., 1994). However, even when T cell responses occurred, they rarely provided protective immunity nor could they be mobilized to provide a basis for therapy.
As demonstrated by elegant analyses of cancer in mice, the continued deletion of cancer cells expressing T cell targets (immune editing) may enable cancers to evolve to avoid attack (Dunn et al., 2002). Despite these findings, recent results from human cancer have demonstrated that overcoming negative regulators to T cell responses in lymphoid organs (checkpoints) and in the tumor bed (immunostat function) are likely to explain the failure of immune protection in many patients (Mullard, 2013). Factors in the tumor microenvironment can act to modulate the existing activated antitumor T cell immune response, acting as an immune rheostat or “immunostat.” This class of molecules, including PD-L1:PD-1 (reviewed in Chen et al., 2012 and Topalian et al., 2012a), emphasizes that the immune response in cancer reflects a series of carefully regulated events that may be optimally addressed not singly but as a group. The challenge now is to use this new understanding to develop new drugs and implement clinical strategies.
The articles contained in this issue each address key aspects of how the immune response can control or be manipulated to enhance anticancer immunity (Galon et al., 2013, Kalos and June, 2013, Motz and Coukos, 2013, Palucka and Banchereau, 2013, van den Boorn and Hartmann, 2013 and Zitvogel et al., 2013). Here, we will integrate this information and consider how it might best be used in clinical development.

CV Rubens Riotorto, MD

Born in Montevideo, Uruguay, Rubens Riotorto MD, is a medical oncologist. He developed his professional career at the National Institute of Oncology, center of reference for the diagnosis and treatment of cancer in the above mentioned country.

Curriculum.
He obtained a scholarship from the Honorary Commission of Fight against Cancer (Uruguay) in the Institute Curie of Paris (France). At the National Institute of Oncology he was chief of service of Chemotherapy, chief of service of Medical Oncology and finally Director of the National Institute of Oncology and, as such, a member of the Committee Board of the Honorary Commission of Fight against Cancer.
In Spain, he worked at Melilla´s Hospital, where he was also the President of the Technical Committee of the Spanish Association against Cancer.
He moved then to Aranda de Duero, where he worked at Santos Reyes Hospital. In the above mention city he was vocal of the Spanish Association against Cancer.
From January 2012 until December 2014, he was chief of service of medical oncology at Diagonal´s Clinic in Barcelona. He was a member of Joaquim Bellmunt´s MD, PhD oncology team from January 2012 until June 2013.
Since January 2015 he is member of Oncosur´s oncology team, the Andalusia´s most important private oncology group.