Putative gene

It refers to a nucleotide sequence believed to be a gene because of its open reading frame although its function and the protein it codes for has not been (fully) identified [1]. For example, putative gene 57 is the (temporary) name suggested for the gene coding for a protein produced by Bacteriophage SP01 that infects the bacterium Bacillus subtilis [2]. Another example: PTEN, a putative protein tyrosine phosphatase gene mutated in some cancers [3].

Bibliographic references:

[1] Biology-online.org. (2014). Putative - Biology-Online Dictionary. [online] Available at: http://www.biology-online.org/dictionary/Putative [Accessed 26 Jun. 2016].

[2] Stewart CR, Gaslightwala I, Hinata K, Krolikowski KA, Needleman DS, Peng AS, et al. Genes and regulatory sites of the "host-takeover module" in the terminal redundancy of Bacillus subtilis bacteriophage SPO1. Virology. 1998 Jul 5; 246 (2): 329-40. Available at: http://dx.doi.org/10.1006/viro.1998.9197.

[3] Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943-7. Available at: http://dx.doi.org/10.1126/science.275.5308.1943.

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].

TARGIT (targeted intraoperative radiotherapy)

It is a technique of giving radiotherapy to the tissues surrounding a cancer after its surgical removal. In patients having lumpectomy for breast cancer, the TARGIT-A(lone) randomized controlled trial [1] tested whether TARGIT within a risk-adapted approach was non-inferior to conventional course of external beam postoperative radiotherapy given over several weeks. The conclusion was TARGIT concurrent with lumpectomy should be considered an option for eligible patients [2]. The ongoing TARGIT-B(oost) randomized controlled trial is testing whether TARGIT tumour bed boost given after lumpectomy for breast cancer in younger patients or those with a high risk of recurrence is superior to conventional external beam radiotherapy boost for breast cancer [3].

The TARGIT technique is performed by low energy X-rays (50kV maximum) at the tip of a tube. The radiation source is inserted into the tumour bed immediately after excision of the tumour and switched on for 20-35 minutes to provide intra-operative radiotherapy accurately targeted to the tissues that are at highest risk of local recurrence [4].

Other nomenclatures: TARGIT-BQR (boost quality registry) [5], TARGIT-C (consolidation) [5], TARGIT-D (ductal carcinoma in situ) [6], TARGIT-E (elderly) [7], TARGIT-R (retrospective) [8], TARGIT-US (United States) [9].

Bibliographic references:

[1] Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, et al;  TARGIT trialists' group. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014 Feb 15;383(9917):603-13. Available at: http://dx.doi.org/10.1016/S0140-6736(13)61950-9.

[2] En.wikibooks.org. (2016). Radiation Oncology/Breast/Partial breast irradiation - Wikibooks, open books for an open world. [online] Available at: https://en.wikibooks.org/wiki/Radiation_Oncology/Breast/Partial_breast_irradiation [Accessed 25 Jun. 2016].

[3] Wikipedia. (2016). Targeted intra-operative radiotherapy. [online] Available at: https://en.m.wikipedia.org/wiki/Targeted_intra-operative_radiotherapy [Accessed 25 Jun. 2016].

[4] Ucl.ac.uk. (2016). TARGIT-B. [online] Available at: http://www.ucl.ac.uk/silva/surgical-interventional-trials-unit/trials/breast/targit-trials/targit-b [Accessed 25 Jun. 2016].

[5] Sperk E, Astor D, Keller A, Welzel G, Gerhardt A, Tuschy B, et al. A cohort analysis to identify eligible patients for intraoperative radiotherapy (IORT) of early breast cancer. Radiat Oncol. 2014; 9: 154. Available at: http://dx.doi.org/10.1186%2F1748-717X-9-154.

[6] Williams, N. and Reynolds, C. (2014). Treating Patients with TARGIT. In: M. Keshtgar, K. Pigott and F. Wenz, ed., Targeted Intraoperative Radiotherapy in Oncology, 1st ed. Springer-Verlag Berlin Heidelberg, pp.141-145.

[7] Neumaier C, Elena S, Grit W, Yasser AM, Uta KT, Anke K, et al. TARGIT-E(lderly)--prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer. BMC Cancer. 2012 May 8;12:171. Available at: http://dx.doi.org/10.1186/1471-2407-12-171.

[8] Valente SA, Tendulkar RD, Cherian S, O'Rourke C, Greif JM, Bailey L, et al. TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer. Ann Surg Oncol. 2016 May 9. Available at: http://dx.doi.org/10.1245/s10434-016-5240-1.

[9] Clinicaltrials.gov. (2016). Targeted Intraoperative Radiotherapy United States (TARGIT-US) Registry Trial - Full Text View - ClinicalTrials.gov. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT01570998 [Accessed 25 Jun. 2016].

PTV (planning target volume)

It includes the gross tumor volume (GTV), the clinical target volume (CTV), and a margin to account for setup error, movement, and any possible geometric variations. The volume that includes the CTV with any internal target volume (ITV), if present, as well as a setup margin to account for patient movement and daily setup uncertainties [1]. When the patient moves or internal organs change in size and shape during a fraction of treatment or between fractions (intra- or inter-fractionally), the position of the CTV may also move. Therefore, to ensure a homogeneous dose to the CTV throughout a fractionated course of irradiation, margins must be added around the CTV. These allow for physiological organ motion (internal margin) and variations in patient positioning and alignment of treatment beams (set-up margin), creating a geometric planning target volume [2]. PTV is the ultimate target volume, the primary focus of the treatment planning and delivery. Adequate dose delivered to PTV at each treatment session, presumably, assures adequate treatment of the entire disease-bearing volume, the CTV [3].

Bibliographic references:

[1] Fisher, B.,  Daugherty, L, Reiff J. E. (2013). P. In: L. Brady and T. Yaeger, ed., Encyclopedia of Radiation Oncology, 1st ed. Springer-Verlag Berlin Heidelberg, pp.585-693.

[2] Barrett, A., Dobbs, J., Morris, S. and Roques, T. ed., (2009). 2 Principles of radiotherapy planning. In: Practical Radiotherapy Planning, 4th ed. London: Hodder Arnold, an Hachette UK Company, pp.9-31.

[3] Khan, F. (2007). Chapter 1 - Introduction: Process, Equipment, and Personnel. In: F. Khan, ed., Treatment Planning in Radiation Oncology, 2nd ed. Lippincott Williams & Wilkins.

Systematic review

It answers a defined research question by collecting and summarising all empirical evidence that fits pre-specified eligibility criteria [1]. It is a thorough, comprehensive, and explicit way of interrogating the medical literature. It typically involves several steps, including asking an answerable question, identifying one or more databases to search, developing an explicit search strategy, selecting titles, abstracts, and manuscripts based on explicit inclusion and exclusion criteria, and abstracting data in a standardized format [2]. They often, but not always, use statistical techniques (meta-analysis) to combine results of eligible studies, or at least use scoring of the levels of evidence depending on the methodology used. While many systematic reviews are based on an explicit quantitative meta-analysis of available data, there are also qualitative systematic reviews which adhere to standards for gathering, analyzing and reporting evidence. A review of existing studies is often quicker and cheaper than embarking on a new study. Systematic reviews of randomized controlled trials are key in the practice of evidence-based medicine [3].

Bibliographic references:

[1] Ccace.ed.ac.uk. (2013). Systematic reviews and meta-analyses: a step-by-step guide | www.ccace.ed.ac.uk. [online] Available at: http://www.ccace.ed.ac.uk/research/software-resources/systematic-reviews-and-meta-analyses [Accessed 21 Jun. 2016].

[2] Researchcore.org. (2016). ResearchCore.org - What is the difference between a "systematic review" and a "meta-analysis"?. [online] Available at: http://www.researchcore.org/faq/answers.php?recID=5 [Accessed 21 Jun. 2016].

[3] Wikipedia. (2016). Systematic review. [online] Available at: https://en.wikipedia.org/wiki/Systematic_review [Accessed 21 Jun. 2016].

Meta-analysis

It is a statistical process by which the results of several studies, frequently randomized clinical trials, are combined to develop a single estimate of the effect of an intervention, treatment, or exposure on disease [1]. It is a specific type of systematic analysis that uses a quantitative method to combine data from two or more studies. It is a series of systematic methods for combining data from more than one investigation in order to draw conclusions that could not be drawn from a single investigation [2]. Therefore, every meta-analysis should be based on an underlying systematic review, but not every systematic review leads to a meta-analysis [3]. It gives a pretty good idea about the best trend to go with, which is supported by multiple studies, with a larger number of patients (by Dr. Nabil Mobarek, Medical Advisor Oncology at Eli Lilly and Company).

It «is a statistical method for combining the information residing in the summary statistics, say odds ratios and their standard errors, from a group of independent studies, e.g., clinical trials, of a given treatment or diagnostic procedure. In biochemical and epidemiological investigations it is usually undertaken to achieve one of two aims: (1) obtaining pooled point and interval estimates of an overall "true treatment effect". (2) "borrowing strength" across a group of studies to obtain improved point and interval estimates. There are four models of meta-analysis: fixed effects, random effects, mixed effects, and Stein effects. The first three models are used to achieve the first aim. The last two are used to achieve the second aim. The Stein, or empirical Bayes model, like most Bayes models, provides a useful answer to the extrapolation problem often described as Bernard's dilemma: The response of the "average" patient to therapy is not necessarily the response of the patient being treated [4].»

Bibliographic references:

[1] Balcer, L. (n.d.). Basic Epidemiologic and Biostatistics Terminology. [online] Available at: http://content.lib.utah.edu:81/cgi-bin/showfile.exe?CISOROOT=/ehsl-nam&CISOPTR=1175&filename=1176.pdf [Accessed 20 Jun. 2016].

[2] Riegelman, R. (2005). Most Frequently Used Terms in Biostatistics. In: Studying a study and testing a test. Philadelphia: Lippincott Williams & Wilkins, pp.1-38.
[3] Researchcore.org. (2016). ResearchCore.org - What is the difference between a "systematic review" and a "meta-analysis"?. [online] Available at: http://www.researchcore.org/faq/answers.php?recID=5 [Accessed 21 Jun. 2016].

[4] Deasy JO, et al.; AAPM/NIH. Methodological issues in radiation dose-volume outcome analyses: summary of a joint AAPM/NIH workshop. Med Phys. 2002 Sep;29(9):2109-27. Available at: https://doi.org/10.1118/1.1501473.

MeSH (medical subject headings)

It is the United States National Library of Medicine controlled vocabulary thesaurus used for indexing articles for PubMed.

Bibliographic reference: Ncbi.nlm.nih.gov. (n.d.). Home - MeSH - NCBI. [online] Available at: http://www.ncbi.nlm.nih.gov/mesh [Accessed 13 Jun. 2016].

CTV (clinical target volume)

CTV includes the GTV as well as the regions of direct, local subclinical spread of disease that must be treated. The CTV often has a high tumor cell density nearest the GTV with decreasing density toward the periphery. The CTV volumes may not contain demonstrable tumor but are considered at risk, such as regional lymph nodes and their volumes, for subclinical spread.

Bibliographic reference:  Fisher, B. and Daugherty, L. (2013). C. In: L. Brady and T. Yaeger, ed., Encyclopedia of Radiation Oncology, 1st ed. Springer-Verlag Berlin Heidelberg, pp.77-154.

Shaving or shave biopsy

It is a biopsy of a skin lesion by excising it with a cut parallel to the surface of the surrounding skin.

Bibliographic reference: TheFreeDictionary.com. (2012). shave biopsy. [online] Available at: http://medical-dictionary.thefreedictionary.com/shave+biopsy [Accessed 5 Jun. 2016].

Split course

It is a set of fractions planned and prescribed as a whole with a period of no treatment during them [1]. Split-course radiation therapy is an altered fractionation regimen originally designed to diminish radiation morbidity by splitting the total dose into at least two separate courses with an interruption of 10 to 14 days [2]. It allows  the body recovers while the cancer shrinks [3]. It may be disadvantageous compared with continuous treatment because the decreased radiation morbidity of normal tissues will also result in lower anti-tumour efficiency and reduced local control rates. There is also concern about repopulation during the rest period [4]. There are at least three regimens of split-course radiotherapy [5]:

1. Standard total treatment dose at 1.8 to 2.0 Gy fraction size, but with different total treatment time and an interruption interval of one to two weeks;
2. Standard total treatment dose but different fraction size to maintain the same overall treatment time including the interruption interval of one to two weeks;
3. Different total treatment dose, fraction size, overall treatment time and interruption interval.

Bibliographic references:
[1] Datadictionary.nhs.uk. (2016). Supporting Information: Radiotherapy Treatment Course. [online] Available at: http://www.datadictionary.nhs.uk/data_dictionary/nhs_business_definitions/r/radiotherapy_treatment_course_de.asp?shownav=1 [Accessed 2 Jun. 2016].

[2] Scanlon TW. Split dose radiotherapy: the original premise. Int J Radiat Oncol Biol Phys 1980;6:527-8. Available at: http://dx.doi.org/10.1016/0360-3016(80)90072-3.

[3] Cancer.org. (2015). External radiation therapy. [online] Available at: http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/radiation/understandingradiationtherapyaguideforpatientsandfamilies/understanding-radiation-therapy-external-radiation-therapy [Accessed 2 Jun. 2016].

[4] Parsons JT, Bova FJ, Million RR. A re-evaluation of split-course technique for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 1980;6:1645-52. Available at: http://dx.doi.org/10.1016/0360-3016(80)90246-1.

[5] Members of the Lung Cancer Disease Site Group. Altered fractionation of radical radiation therapy in the management of unresectable non-small cell lung cancer. Toronto (ON): Cancer Care Ontario; 2002 Sep [Endorsed 2012 Nov]. Program in Evidencebased Care Practice Guideline Report No.: 7-12 Version 2. Available at: https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=14170 [Accessed 2 Jun. 2016].