Sunday, 7 July 2019

Intraepithelial neoplasia (IEN)

It «is the development of a benign neoplasia or high-grade dysplasia in an epithelium. The exact dividing line between dysplasia and neoplasia has been very difficult to draw throughout the era of medical science. It varies between persons. (...). It is not cancer, but it is associated with higher risk for developing cancer in future. It is thus sometimes a precancerous condition [1].» «The changes in the cells may be low grade or high grade, (...) [2].»  «Dysplasia can be low-grade or high-grade. High-grade dysplasia may also be referred to as carcinoma in situ [3].» It is «an in situ carcinoma confined to an epithelium that may superficially penetrate adnexal glands, measuring < either 3 mm or 5 mm depending on the criteria used. Abnormal cell growth that is found within epithelial cells but has not yet spread to neighboring, underlying, or distant tissues [4].» It is «a proliferation of malignant-appearing cells without evidence of invasion through the epithelial basement membrane [5].»

Evolution of cancer:
Source: Oncology (Cancer) - Health Facts [Internet]. Ndhealthfacts.org. 2017 [cited 2019 Jul 7]. Available from: http://www.ndhealthfacts.org/wiki/Oncology_%28Cancer%29.

Vulval intraepithelial neoplasia (VIN):
Source: Vulval intraepithelial neoplasia (VIN) | Vulval cancer | Cancer Research UK [Internet]. Cancerresearchuk.org. 2019 [cited 2019 Jul 7]. Available from: https://www.cancerresearchuk.org/about-cancer/vulval-cancer/stages-types-grades/vulval-intraepithelial-neoplasia.

Bibliographic references:
[1] Intraepithelial neoplasia [Internet]. En.wikipedia.org. 2015 [cited 2019 Jul 7]. Available from: https://en.wikipedia.org/wiki/Intraepithelial_neoplasia.
[2] NCI Dictionary of Cancer Terms [Internet]. National Cancer Institute. [cited 2019 Jul 7]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/intraepithelial-neoplasia.
[3] Carcinoma in situ [Internet]. En.wikipedia.org. 2019 [cited 2019 Jul 7]. Available from: https://en.wikipedia.org/wiki/Carcinoma_in_situ.
[4] Intraepithelial neoplasia [Internet]. TheFreeDictionary.com. [cited 2019 Jul 7]. Available from: https://medical-dictionary.thefreedictionary.com/intraepithelial+neoplasia.
[5] Wazer DE. In Situ Carcinoma. In: Brady L. Encyclopedia of radiation oncology. Berlin: Springer; 2013. p. 373.

Wednesday, 29 May 2019

Targeted therapy

There are «some of the differences within cancer cells that enable them to thrive. Targeted therapy refers to treatment with drugs that have been developed to “target” these differences within the cell. Unlike chemotherapy, targeted therapy drugs alter the inner workings of the cell focusing on the part of the cancer cell that makes it different from the normal (...). Because they leave the healthy cells alone the side effects of targeted therapies are different from standard chemotherapy treatments. Targeted therapy works by one of the following: arresting the development of new blood vessels that feed the cancer cell, triggering the immune system to attack the cancer cell, changing proteins within the cancer cell, blocking or turning off signals telling the cancer cell to grow or divide, or carrying toxins directly to the cancer cell [1].»
It is «a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Some targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells. Other types of targeted therapies help the immune system kill cancer cells or deliver toxic substances directly to cancer cells and kill them. Targeted therapy may have fewer side effects than other types of cancer treatment. Most targeted therapies are either small molecule drugs or monoclonal antibodies [2].»
«Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules ("molecular targets") that are involved in the growth, progression, and spread of cancer. (...). Many different targeted therapies have been approved for use in cancer treatment. These therapies include hormone therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapies, and toxin delivery molecules.
  • Hormone therapies slow or stop the growth of hormone-sensitive tumors, which require certain hormones to grow. Hormone therapies act by preventing the body from producing the hormones or by interfering with the action of the hormones. Hormone therapies have been approved for both breast cancer and prostate cancer. 
  • Signal transduction inhibitors block the activities of molecules that participate in signal transduction, the process by which a cell responds to signals from its environment. During this process, once a cell has received a specific signal, the signal is relayed within the cell through a series of biochemical reactions that ultimately produce the appropriate response(s). In some cancers, the malignant cells are stimulated to divide continuously without being prompted to do so by external growth factors. Signal transduction inhibitors interfere with this inappropriate signaling. 
  • Gene expression modulators modify the function of proteins that play a role in controlling gene expression. 
  • Apoptosis inducers cause cancer cells to undergo a process of controlled cell death called apoptosis. Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells. 
  • Angiogenesis inhibitors block the growth of new blood vessels to tumors (a process called tumor angiogenesis). A blood supply is necessary for tumors to grow beyond a certain size because blood provides the oxygen and nutrients that tumors need for continued growth. Treatments that interfere with angiogenesis may block tumor growth. Some targeted therapies that inhibit angiogenesis interfere with the action of vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation. Other angiogenesis inhibitors target other molecules that stimulate new blood vessel growth. 
  • Immunotherapies trigger the immune system to destroy cancer cells. Some immunotherapies are monoclonal antibodies that recognize specific molecules on the surface of cancer cells. Binding of the monoclonal antibody to the target molecule results in the immune destruction of cells that express that target molecule. Other monoclonal antibodies bind to certain immune cells to help these cells better kill cancer cells.
  • Monoclonal antibodies that deliver toxic molecules can cause the death of cancer cells specifically. Once the antibody has bound to its target cell, the toxic molecule that is linked to the antibody — such as a radioactive substance or a poisonous chemical — is taken up by the cell, ultimately killing that cell. The toxin will not affect cells that lack the target for the antibody — i.e., the vast majority of cells in the body.
Cancer vaccines and gene therapy are sometimes considered targeted therapies because they interfere with the growth of specific cancer cells [3].»
Bibliographic references: 
[1] Cancer-champions.com. (n.d.). Chemotherapy, Immunotherapy, Targeted Therapy. What's the difference? | Cancer-Champions health-care consulting. [online] Available at: https://cancer-champions.com/chemotherapy-immunotherapy-targeted-therapy-whats-the-difference/ [Accessed 29 May 2019].
[2] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/targeted-therapy [Accessed 29 May 2019].
[3] National Cancer Institute. (n.d.). Targeted Cancer Therapies. [online] Available at: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet [Accessed 29 May 2019].

Immunotherapy

It uses «the body’s immune system to fight cancer cells by stimulating the immune system. (...). Immunotherapy may be used by itself or with other types of treatment. The main types of immunotherapy being used to treat cancer include: monoclonal antibodies, immune checkpoint inhibitors, and cancer vaccines [1].»
It is «a type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies [2].»

It is a type of targeted therapy.
Bibliographic references: 
[1] Cancer-champions.com. (n.d.). Chemotherapy, Immunotherapy, Targeted Therapy. What's the difference? | Cancer-Champions health-care consulting. [online] Available at: https://cancer-champions.com/chemotherapy-immunotherapy-targeted-therapy-whats-the-difference/ [Accessed 29 May 2019]. 
[2] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immunotherapy [Accessed 29 May 2019].

Tuesday, 28 May 2019

AJCC

American Joint Committee on Cancer

Regional lymph nodes in rectal cancer

Regional lymph nodes are located along the providing vessels of the rectum. The AJCC confines locoregional lymph node involvement to the following lymph nodes:
  • sigmoid mesenteric;
  • inferior mesenteric;
  • superior rectal/hemorrhoidal;
  • middle rectal/hemorrhoidal;
  • inferior rectal/hemorrhoidal;
  • perirectal;
  • sacral promontory (Gerota's);
  • lateral sacral;
  • presacral;
  • internal iliac.
Source: [1].

Lymph nodes outside of these areas are considered metastatic disease (M1) (for example, suspicious inguinal lymph nodes if the distal anal sphincter complex is involved) [1].


Coronal and axial drawings show the nodal stations relevant to anal and rectal cancers. Regional nodal stations are shown for anal cancers (blue-green) and rectal cancers (orange). Nodal stations considered metastatic for both anal and rectal cancer are shaded dark gray. Red and blue circles in the axial drawing are external and internal iliac arteries and veins.
Source: [2].

«Pelvic lymph nodes outside of the mesorectum — internal iliac, external iliac, obturator, and common iliac — are termed lateral pelvic lymph nodes (LPLNs). Rectal cancer with involved LPLNs is managed differently in the United States (US) compared to several countries in Asia. In the US, the AJCC defines only the internal iliac lymph nodes as regional, whereas external and common iliac lymph nodes are considered sites of metastatic disease. On the other hand, in Japan, all LPLNs are considered regional and patients are treated with curative intent [3-4]».

Differences in the understanding and management of LPLNs between the East and the West:
LLN = lateral lymph node; nCRT = neoadjuvant chemoradiotherapy; RT = radiotehrapy.
Source: [5]

Bibliographic references:
[1] van Loenhout R, Zijta F, Lahaye M, Beets-Tan R, Smithuis R. The Radiology Assistant: Rectal Cancer - MR staging 2.0 [Internet]. Radiologyassistant.nl. 2015 [cited 2019 May 28]. Available from: http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-20.html#in565b4b37b539c.
[2] Matalon SA, et al. Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy. Radiographics. 2015 Nov-Dec;35(7):2090-107. Available at: https://doi.org/10.1148/rg.2015150037.
[3] Akiyoshi T, et al. Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease? Ann Surg. 2012 Jun;255(6):1129-34. Available at: https://doi.org/10.1097/SLA.0b013e3182565d9d.
[4] Yahya JB, et al. Does a fine line exist between regional and metastatic pelvic lymph nodes in rectal cancer-striking discordance between national guidelines and treatment recommendations by US radiation oncologists. J Gastrointest Oncol. 2018 Jun;9(3):441-447. Available at: https://doi.org/10.21037/jgo.2018.02.05.
[5] Radjindrin A, Shanmugam V. Does Lateral Pelvic Lymph node matters in rectal cancer. Glob Surg. 2018;4(4):1-3.

Sunday, 26 May 2019

Anorectal anatomy

«Note the anal crypts and glands; 90 percent of anorectal fistulas originate in a cryptoglandular abscess. Also note the relationship of the crypts and glands to the internal and external sphincters.»

«The anal canal is 2.5 to 3.5 cm long and begins superiorly where the rectal ampulla is narrowed by the puborectalis sling (the levator ani muscle, which is palpable as the anorectal ring). It ends at the intersphincteric groove. Externally, the anal canal is surrounded by the internal and external anal sphincter muscles.
The superior half of the anal canal contains a series of longitudinal ridges called the anal columns (of Morgagni), which extend from the anorectal junction superiorly to the anal valves inferiorly. The anal valves form an irregular line called the dentate (or pectinate) line (colored purple in the diagram), which is an important anatomical landmark. The portions of the anal canal superior and inferior to it have different origins of arterial supply, nerve innervation, venous/lymphatic drainage, and epithelial lining.
The anal canal is internally lined with mucous membrane above the dentate line and anoderm below it. The upper portion of the anoderm (anal verge) consists of smooth, hairless skin; the lower portion of the anoderm (perianal skin) contains pigmented skin containing hair follicles and glands.»

Rectal division

Division of the upper, middle, and lower rectum [1]:
Image adapted from Surgical Anatomy of the Colon, Rectum, and Anus [Internet]. Abdominal Key. 2017 [cited 2019 May 29]. Available from: https://abdominalkey.com/surgical-anatomy-of-the-colon-rectum-and-anus/.

Measurement of rectal cancer with respect to the reference level and method:
Source: Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol2012;23(10):2479–516. Available at: https://doi.org/10.1093/annonc/mds236.

«The rectum extends from the anorectal junction to the sigmoid. The rectosigmoid junction is arbitrarily defined as 15 cm above the anorectal angle. A tumor more than 15 cm above the anorectal angle is regarded and treated as a sigmoid tumor. Rectal cancer can be divided into:
- Low rectal cancer: distal border is 0-5 cm from the anorectal angle;
- Mid rectal cancer: distal border is 5-10 cm from the anorectal angle;
- High rectal cancer: distal border is 10-15 cm from the anorectal angle.»
Source: The Radiology Assistant: Rectal Cancer - MR staging 2.0 [Internet]. Radiologyassistant.nl. 2015 [cited 2019 May 26]. Available from: http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-20.html.


Bibliographic references:

Thursday, 28 March 2019

Siewert classification

AC = anatomical cardia
Source: Ulla M, et al. Esophageal cancer characterization with pneumo-64-MDCT. Abdom Imaging. 2012 Aug;37(4):501-11. Available at: https://doi.org/10.1007/s00261-011-9784-z.

«The Siewert-Stein classification is a system of anatomical classification used for adenocarcinomas of the esophagogastric junction.»
Bibliographic reference: En.wikipedia.org. (2019). Siewert classification. [online] Available at: https://en.wikipedia.org/wiki/Siewert_classification [Accessed 28 Mar. 2019].

Stomach parts

«This drawing shows the parts of the anterior surface of the stomach. The body of the stomach is separated from the pyloric part by an oblique line that extends from the angular notch (incisura angularis) on the lesser curvature to the greater curvature.»
Source: Uptodate.com. (2019). UpToDate. [online] Available at: https://www.uptodate.com [Accessed 28 Mar. 2019].

Esophageal regions

«Anatomy of esophageal cancer primary site, including typical endoscopic measurements of each region measured from the incisors. Exact measurements depend on body size and height. For tumors of the EGJ and cardia, location of cancer primary site (ie, esophagus, stomach) is defined by cancer epicenter.»
v: vein
Source: Uptodate.com. (2019). UpToDate. [online] Available at: https://www.uptodate.com [Accessed 28 Mar. 2019].

RAS (rat sarcoma) gene

«The word RAS comes from a contraction of Rat sarcoma, the tumor where the first gene of the family was identified, as part of the genome of a retrovirus isolated from a carcinogenesis protocol [3].» It is «a family of genes that make proteins involved in cell signaling pathways (cellular signal transduction [2]) that control cell growth and cell death [1].» «RAS is a guanosine-nucleotide-binding protein. Specifically, it is a single-subunit small GTPase [2]». «When RAS is switched on by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growthdifferentiation, and survival. (...). RAS-regulated signal pathways control such processes as actin cytoskeletal integrity, cell proliferationcell differentiationcell adhesionapoptosis, and cell migration [2].» «Mutated (changed) forms of the RAS gene may be found in some types of cancer. These changes may cause cancer cells to grow and spread in the body [1].» «Mutations in RAS genes can lead to the production of permanently activated RAS proteins. As a result, this can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. (...). The 3 RAS genes in humans (HRASKRAS, and NRAS) are the most common oncogenes in human cancer; mutations that permanently activate RAS are found in 20% to 25% of all human tumors and up to 90% in certain types of cancer (e.g.pancreatic cancer). For this reason, RAS inhibitors are being studied as a treatment for cancer and other diseases with RAS overexpression [2]
«HRAS was initially isolated from the Harvey sarcoma virus. KRAS from the Kirsten sarcoma virus and NRAS was isolated by DNA [deoxyribonucleic acid]-mediated gene transfer from a human neuroblastoma cell line [3].»
«RAS gene mutations are among the most frequently mutated genes in human cancers, found in approximately 30% of all tumor types and in approximately 50% of colorectal cancer (CRC). (...). In addition, oncogenic RAS mutations cause acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies such as cetuximab and panitumumab. Given its clinical relevance as an important predictive biomarker, the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines recommend RAS testing for KRAS and NRAS mutations in exon 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) when managing patients with metastatic colorectal cancer. [4].»
Bibliographic references:
[1] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ras-gene-family [Accessed 28 Mar. 2019].
[2] En.wikipedia.org. (2019). Ras subfamily. [online] Available at: https://en.wikipedia.org/wiki/Ras_subfamily [Accessed 28 Mar. 2019].
[3] Pellicer A. (2011) RAS Genes. In: Schwab M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. Available at: https://doi.org/10.1007/978-3-642-16483-5_4951.
[4] Scott AJ, et alTherapeutic Approaches to RAS Mutation. Cancer J. 2016 May-Jun; 22(3): 165–174. Available at: https://dx.doi.org/10.1097/PPO.0000000000000187.

Friday, 22 March 2019

Spinal cord end

«In humans, the spinal cord stops growing in infancy and the end of the spinal cord is about the level of the third lumbar vertebra, or L3, at birth. Because the bones of the vertebral column continue to grow, by about 12 months of age, the end of the cord reaches its permanent position at the level of L1 or L2 (closer to the head). However, due to normal anatomical variations, the final cord end position may occur anywhere from the twelfth thoracic vertebra (T12) to L3.»

Source: Spine and Pelvis [Internet]. Musculoskeletal Key. 2016 [cited 2019 Jul 7]. Available from: https://musculoskeletalkey.com/spine-and-pelvis-3/.

Bibliographic reference: En.m.wikipedia.org. (n.d.). Cauda equina. [online] Available at: https://en.m.wikipedia.org/wiki/Cauda_equina [Accessed 27 Mar. 2019].

Thursday, 21 March 2019

Hypopharynx

«The hypopharynx or laryngopharynx forms the most inferior portion of the pharynx, being the continuation of the oropharynx superiorly and both the larynx and esophagus inferiorly. The hypopharynx begins as the continuation of the oropharynx at the pharyngoepiglottic fold (which is at the level of the hyoid bone) superiorly, and extends inferiorly to the level of the inferior aspect of the cricoid cartilage, where it continues as the cervical esophagus. It is a mucosa-lined, muscular tube with its posterolateral walls formed by the inferior constrictor muscle and anterior wall by laryngeal cartilages. It forms part of the pharyngeal mucosal space.
The  boundaries are:
  • anteriorly: post-cricoid mucosa, posterior cricoarytenoid muscle;
  • posteriorly: mucosal wall, middle and inferior constrictor muscles;
  • superiorly: hyoid bone, glossoepiglottic and pharyngoepiglottic folds;
  • inferiorly: cricoid cartilage, cricopharyngeus muscle.
Three subsites of the hypopharynx are described, being pertinent to localize where squamous cell carcinoma arises:
  • pyriform sinus;
  • posterior wall;
  • post-cricoid region/pharyngo-esophageal junction: forms the anterior wall [1].»
«Embryologically, the larynx interjects into the hypopharynx anteriorly and is therefore considered a separate structure. Hypopharyngeal cancers are often named for their location, including pyriform sinus, lateral pharyngeal wall, posterior pharyngeal wall, or post-cricoid pharynx [2].»


Illustration of the pharynx:
Source: Commons.wikimedia.org. (n.d.). File:2411 Pharynx.jpg - Wikimedia Commons. [online] Available at: https://commons.wikimedia.org/wiki/File:2411_Pharynx.jpg [Accessed 21 Mar. 2019].

«The hypopharynx is the longest of the 3 segments of the pharynx. It is wide superiorly and progressively narrows toward the level of the cricopharyngeal muscle. It is bounded anteriorly by the posterior face of the cricoid cartilage. The parts of the hypopharynx that lie partly to each side of the larynx form the pyriform sinuses or fossae [2].»
Source: [2].

Source: [2].

Bibliographic references:
[1] Deng, F. and Knipe, H. (2018). Hypopharynx | Radiology Reference Article | Radiopaedia.org. [online] Radiopaedia.org. Available at: https://radiopaedia.org/articles/hypopharynx [Accessed 21 Mar. 2019].

[2] Quon, H. and Goldenberg, D. (2017). Hypopharyngeal Cancer: Overview, Clinical Presentation, Etiology and Risk Factors. [online] Emedicine.medscape.com. Available at: https://emedicine.medscape.com/article/1375268-overview [Accessed 21 Mar. 2019].

Thursday, 14 March 2019

Primary treatment

It is «the first treatment given for a disease. It is often part of a standard set of treatments, such as surgery followed by chemotherapy and radiation. When used by itself, primary treatment is the one accepted as the best treatment. If it doesn’t cure the disease or it causes severe side effects, other treatment may be added or used instead. Also called first-line therapy, induction therapy, and primary therapy.»
Bibliographic reference: National Cancer Institute. NCI Dictionary of Cancer Terms. Primary treatment. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/primary-treatment. Accessed 2019 Mar 14.

Monday, 11 March 2019

Cancer-related survival

It is the time from diagnosis of cancer, or the start of treatment for cancer, to the date of death related to primary cancer.
Bibliographic reference: Wu YC, et al. Long-term results of pathological stage I non-small cell lung cancer: validation of using the number of totally removed lymph nodes as a staging control. Eur J Cardiothorac Surg. 2003 Dec;24(6):994-1001. Available at: https://doi.org/10.1016/S1010-7940(03)00567-0.

Late side effects of radiotherapy

Toxicity typically occurring more than 3 months after treatment.
Bibliographic reference: Peach MS, et al. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer. Prostate Cancer. 2015;2015:624736. Available at: https://doi.org/10.1155/2015/624736.

Acute side effects of radiotherapy

Toxicity typically occurring within 3 months of treatment.
Bibliographic reference: Peach MS, et al. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer. Prostate Cancer. 2015;2015:624736. Available at: https://doi.org/10.1155/2015/624736.

Saturday, 9 March 2019

Definitive treatment

«The treatment plan for a disease or disorder that has been chosen as the best one for a patient after all other choices have been considered [1]». It is «any therapy generally accepted as a specific cure of a disease [2]». It «is the first clinical intervention intended to manage a patient's disease, condition or injury and avoid further clinical interventions [3]». It is «a therapy that may be final, superior to others, curative, or all of those [4]». For example, definitive radiation is the «administration of radiation as a sole or first therapy, usually for cancer, with curative intent [5]».
Bibliographic references:
[1] National Cancer Institute. NCI Dictionary of Cancer Terms(n.d.). Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/definitive-treatment [Accessed 9 Mar. 2019].
[2] TheFreeDictionary.com. (n.d.). definitive treatment. [online] Available at: https://medical-dictionary.thefreedictionary.com/definitive+treatment [Accessed 9 Mar. 2019].
[3] Datadictionary.nhs.uk. (2018). Supporting Information: First Definitive Treatment. [online] Available at: https://www.datadictionary.nhs.uk/data_dictionary/nhs_business_definitions/f/first_definitive_treatment_de.asp?shownav=1 [Accessed 9 Mar. 2019].
[4] En.wikipedia.org. (2019). Therapy. [online] Available at: https://en.wikipedia.org/wiki/Therapy#Lines_of_therapy [Accessed 9 Mar. 2019].
[5] TheFreeDictionary.com. (n.d.). definitive radiation. [online] Available at: https://medical-dictionary.thefreedictionary.com/definitive+radiation [Accessed 9 Mar. 2019].