Repeatability

It is a measure of precision. It is the «variation due to the measuring device. It is the variation observed when the same operator measures the same part repeatedly with the same device [1].» It «is similar to uniformity except that it deals with how consistent a particular sensor is against itself. It can be used to describe the ability of a sensor to provide the same result, under the same circumstances, over and over again [2].»

Bibliographic references:

[1] Reliawiki. 2017. Measurement System Analysis. [online] Available at: <https://reliawiki.org/index.php/Measurement_System_Analysis> [Accessed 20 February 2022].

[2] Apogeeinstruments.com. 2022. Uniformity, Repeatability, Stability, and Accuracy. [online] Available at: <https://www.apogeeinstruments.com/uniformity-repeatability-stability-and-accuracy/> [Accessed 20 February 2022].

Rare cancers

The definition of rare tumors is not consensual. Rare cancers are defined as an incidence of fewer than 6 cases per 100.000 individuals per year (RARECARE workin group, Gatta et al. Eur J Cancer 2011).

According to DeSantis et al. ACS Atlanta. CA Cancer J Clin 2017, overall, approximately 20% of patients with cancer in the United States are diagnosed with a rare cancer. Based on the RARECARE workin group, Gatta et al. Eur J Cancer 2011, rare cancers are about 22% of all cancer diagnoses in Europe and 24% of the total cancer prevalence.

Rare cancers include > 300 histological subtypes and may affect all organs (Morfouace et al. EORTC, ESMO Open 2020). In addition, they can be grouped within 12 families of rare cancers (Casali et al. Fondazione IRCCS INT, Milan, ESMO Open 2020):

1. Epithelial tumours of head and neck:
• Larynx;
• Hypopharynx;
• Nasal cavity and sinuses;
• Nasopharynx;
• Major salivary glands and salivary gland type tumours;
• Oropharynx;
• Oral cavity and lip;
• Eye and adnexa;
• Middle ear.
2. Epithelial digestive tumours:
• Small intestine;
• Anal canal;
• Gallbladder and extrahepatic biliary duct.
3. Thoracic tumours:
• Epithelial tumours of the trachea;
• Thymomas and thymic carcinomas;
• Malignant mesothelioma.
4. Female genital tumours:
• Non-epithelial tumours of the ovary;
• Epithelial tumours of the vulva and vagina;
• Trophoblastic tumours of the placenta.
5. Male genital and urogenital tumours:
• Tumours of the testis and paratestis;
• Epithelial tumours of penis;
• Extragonadal germ cell tumours;
• Epithelial tumours of renal pelvis, ureter, and urethra.
6. Skin cancers and non-cutaneous melanoma:
• Mucosal melanoma;
• Uveal melanoma;
• Adnexal skin carcinomas;
• Kaposi sarcoma.
7. Sarcomas:
• Soft tissue sarcoma;
• Bone sarcoma;
• Gastrointestinal stromal tumours.
8. Neuroendocrine tumours:
• Gastrointestinal pancreatic;
• Lung;
• Other sites.
9. Endocrine organ tumours:
• Thyroid cancers;
• Parathyroid cancer;
• Adrenal cortex cancer;
• Pituitary gland cancer.
10. Central nervous system tumours:
• Glial tumours and others;
• Malignant meninioma;
• Embryonal tumours.
11. Paediatric tumours:
• Hepatoblastoma;
• Neuroblastoma and ganglioneuroblastoma;
• Nephroblastoma;
• Odontogenic malignant tumours;
• Olfactory neuroblastoma;
• Pancreatoblastoma;
• Pleuropulmonary blastoma;
• Retinoblastoma.
12. Haematological malignancies:
• Lymphoid malinancies;
• Myelodysplasctic syndromes;
• Myeloproliferative neoplasms (including mastocytosis);
• Myelodysplastic/myeloproliferative neoplasms;
• Myeloid/lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA (platelet derived growth factor receptor alpha), PDGFRB (platelet derived growth factor receptor beta), or FGFR1 (fibroblast growth factor receptor 1), or with PCM1-JAK2 (pericentriolar material 1-janus kinase 2);
• Acute myeloid leukaemia and related neoplasms.

Then, rare cancers are not so rare, and they are associated with multiple challenges including late and incorrect diagnosis, adverse outcomes, limited clinical expertise, weak evidence for best practice, and difficulties in collecting large series for research and in carrying out clinical trials (Boyd et al. BCCA, Vancouver, Lancet Oncol 2016).

Therefore, a global strategy is needed to join efforts to increase knowledge of this group of cancers.

Rs of radiobiology

The most important biological factors influencing tumor and normal tissue responses to fractionated treatment are referred to as the Rs [1]:

1. Repair [1]/Recovery [2];
2. Re-assortment/Redistribution [1,2];
3. Repopulation [1,2];
4. Reoxygenation [1,2];
5. Radiosensitivity [1,2];
6. Reactivation of anti-tumor immune response [1];
7. intrinsic Radiosensitivity [2];
8. iRradiated volume [2];
9. long-term Restoration [2];
10. molecular Radiopathology [2].

Bibliographic references:

[1] Boustani J, Grapin M, Laurent PA, Apetoh L, Mirjolet C. The 6th R of Radiobiology: Reactivation of Anti-Tumor Immune Response. Cancers (Basel). 2019 Jun 20;11(6):860. Available at: https://dx.doi.org/10.3390%2Fcancers11060860.

[2] Dörr W. Radiobiology of tissue reactions. Ann ICRP. 2015;44(1 Suppl):58–68. Available at: https://doi.org/10.1177/0146645314560686.

Radiobiology - Introduction (Radiobiologia - Introdução [Portuguese])

(Portuguese)

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 or mesorectal;
• 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. Available at: https://doi.org/10.15761/GOS.1000196.

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 Oncol. 2012;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:

[1] UpToDate [Internet]. Uptodate.com. 2019 [cited 2019 May 26]. Available from: https://www.uptodate.com/contents/image?imageKey=SURG%2F107991&topicKey=SURG%2F17127&search=rectum%20anatomy&source=outline_link&selectedTitle=1~150.

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 growth, differentiation, and survival. (...). RAS-regulated signal pathways control such processes as actin cytoskeletal integrity, cell proliferation, cell differentiation, cell adhesion, apoptosis, 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 (HRAS, KRAS, 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 al. Therapeutic Approaches to RAS Mutation. Cancer J. 2016 May-Jun; 22(3): 165–174. Available at: https://dx.doi.org/10.1097/PPO.0000000000000187.

Disease-free survival (DFS) or relapse-free survival (RFS)

In cancer, the length of time after the end of primary treatment for cancer and that the patient survives without any signs or symptoms of that cancer. In a clinical trial, measuring the DFS is one way to see how well a new treatment works [1].

It includes local, regional, or distant recurrence and death due to any cause.

Bibliographic references:

[1] National Cancer Institute. NCI Dictionary of Cancer Terms. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dfs. Accessed November 21, 2018.

Reoxygenation

Repopulation

Ratio of free to total PSA (prostate-specific antigen)

«The end product of normal PSA (prostate-specific antigen) biosynthesis within the prostate epithelium and ducts is inactive "free PSA", a fraction of which diffuses into circulation. In prostate cancer, tumors disrupt the prostate basement membrane and allow precursor forms of PSA to leak into the circulation, which decreases the relative proportion of free PSA. Hence, the ratio of free-to-total PSA will be lower in men with prostate cancer. A ratio of <7% is highly suspicious for prostate cancer, whereas a ratio of >25% is rarely associated with malignancy.»

Bibliographic reference: Shah A. 53 - Low-Risk Prostate Cancer. In: Hristov B, Lin S, Christodouleas J. Radiation Oncology. 2nd ed. Philadelphia, USA: Wolters Klumer Health; 2015:366.

Ratio

It's the relationship between two sets with different characteristics. The numerator is not included in the denominator. It is different from proportion.

Redistribution

«Reassortment. The radiosensitivities of cells vary according to phases of the cell cycle.» «The duration of the cell cycle phases are: G1 = 1.5–14 h, S = 6–9 h, G2 = 1–5 h, and M = 0.5–1 h. The most sensitive are M and G2. The most resistant is S.» «Cells in the resistant phases of the cell cycle may progress into the sensitive phases in the next fraction, when radiation is given in fractions. Therefore, the probability of tumor cells to be exposed to radiation at sensitive phases increases. This probability will continue for the whole treatment, and the benefit from radiation will increase.»

Bibliographic reference: Beyzadeoglu M, Ozyigit G, Selek U. Radiation Oncology. 1st ed. Berlin: Springer; 2012:112-114.

Radiodermatitis or radiation dermatitis

It «is a cutaneous inflammatory reaction to exposure to biologically effective levels of ionizing radiation» [1]. It «can range from erythema to wet desquamation of the skin (tissue sloughing) in acute form; tissue atrophy, fibrosis, and permanent scarring in chronic form. Permanent changes in skin pigmentation can also occur» [2].

Source: Aistars J, Vehlow K. Radiation Dermatitis | Cancer Network. Cancernetworkcom. 2007. Available at: http://www.cancernetwork.com/oncology-nursing/radiation-dermatitis. Accessed March 30, 2018.

Source: Madhavan R. Radiation in oral cancers. Slidesharenet. 2017. Available at: https://www.slideshare.net/ramumpanicker/radiation-in-oral-cancers. Accessed March 30, 2018.

How to care for your skin during radiation therapy:

Bibliographic references:
[1] Radiodermatitis. (n.d.) Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. (2003). Retrieved January 7 2017 from http://medical-dictionary.thefreedictionary.com/radiodermatitis.
[2] Radiation dermatitis. (n.d.) Medical Dictionary for the Health Professions and Nursing. (2012). Retrieved January 7 2017 from http://medical-dictionary.thefreedictionary.com/radiation+dermatitis.

Recurrence (or relapse)

It is the reappearance of cancer after a disease-free period [1,2]. Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body [3]. Generally, it is the return of a disease or the signs and symptoms of a disease after a period of improvement [4].

Relapse (not recurrence) also refers to returning to the use of an addictive substance or behavior, such as cigarette smoking [4].

Bibliographic references:

[1] CureSearch for Children's Cancer. (n.d.). Relapse or Recurrence. [online] Available at: http://curesearch.org/Relapse-or-Recurrence [Accessed 25 Jun. 2016].

[2] CureSearch for Children's Cancer. (2015). relapse. [online] Available at: http://curesearch.org/glossary/relapse/ [Accessed 25 Jun. 2016].

[3] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45861 [Accessed 25 Jun. 2016].

[4] National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. [online] Available at: http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45866 [Accessed 25 Jun. 2016].

RANO (Response Assessment in Neuro-Oncology) criteria

They are used to assess response to first-line treatment of glioblastoma (as well as lower grade astrocytoma). They divides response into 4 types based on magnetic resonance imaging (MRI) and clinical features: 1) complete response, 2) partial response, 3) stable disease, and 4) progression.

A measurable lesions is measured as follows: either computed tomography or MRI, contrast enhancing, clearly defined margins, visible on two or more axial slices (preferably <5 mm thick with 0 mm skip), maximal diameter and second perpendicular measurement at least 10 mm in size (if slice thickness <5 mm), or 2 times slice thickness (if slice thickness >5 mm), and do not measure cystic cavity. Non-measurable lesions are generally those that do not meet the criteria above. Additionally, and worthy of specific mention, is a cystic/necrotic tumour, or one with a surgical cavity. In such cases only a solid peripheral nodular component should be measured, provided it fulfills the above "measurable" criteria. The measurements are obtained from axial post contrast T1 images. The maximal diameter is obtained, and then the second diameter is obtained at right angles to the first. The product of these measurements is then used for the purpose of comparison.

Criteria for complete response: imaging (disappearance of all enhancing disease [measurable and non-measurable], sustained for at least 4 weeks, stable or improved non enhancing fluid attenuation inversion recovery [FLAIR]/T2 lesions, and no new lesions) and clinical features (no corticosteroids [physiological replacement doses allowed], and clinically stable or improved.

Criteria for partial response: imaging (50% or more decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no progression of non-measurable disease, stable or improved non enhancing FLAIR/T2 lesions, and no new lesions) and clinical features (stable or reduced corticosteroids [compared to baseline], and clinically stable or improved).

Criteria for stable disease: imaging (does not qualify for complete response, partial response or progression, and stable non-enhancing FLAIR/T2 lesions) and clinical features (stable or reduced corticosteroids [compared to baseline] and clinically stable).

Criteria for progression: imaging (25% of more increase in enhancing lesions despite stable or increasing steroid dose, increase [significant] in non-enhancing T2/FLAIR lesions, not attributable to other non-tumour causes, and any new lesions) and clinical features (clinical deterioration [not attributable to other non-tumour causes and not due to steroid decrease]).

Bibliographic reference: Luijkx, T. and Gaillard, F. (2016). RANO criteria for glioblastoma | Radiology Reference Article | Radiopaedia.org. [online] Radiopaedia.org. Available at: http://radiopaedia.org/articles/rano-criteria-for-glioblastoma [Accessed 21 May 2016].

Radiate

To diverge or spread from the common center. To issue and raise. It shares a common root and related meanings with other English words such as ray, radius, and radial.

Bibliographic reference: Halperin E, Wazer D, Perez C. Chapter 1 - The Discipline of Radiation Oncology. In: Halperin E, Wazer D, Perez C, Brady L, ed. Perez and Brady's - Principles and Practice of Radiation Oncology. 6th ed. Philadelphia, USA: Lippincott Williams & Wilkins, a Wolters; 2013. Box 1.2 - The Etymology of Radiate.

RE (relative effectiveness)

One multiplies total dose by RE to obtain BED. RE=(1+d/α/β), where d is the dose per fraction.
Bibliographic reference: Fowler, J. (2006). Part I: Basic Concepts in Treatment Planning, 1. Practical Time-Dose Evaluations, or How to Stop Worrying and Learn to Love Linear Quadratics. In: S. Levitt, J. Purdy, C. Perez and S. Vijayakumar, ed., Technical Basis of Radiation Therapy, Practical Clinical Applications, 4th ed. Springer-Verlag Berlin Heidelberg, pp.3-31.

RTOG

Radiation Therapy Oncology Group.

Bibliographic reference: Rtog.org. (2016). RTOG > Home. [online] Available at: https://www.rtog.org/ [Accessed 1 May 2016].