Tpot (potential doubling time without cell loss)

It describes the proliferation rate of the tissues, which can be measured from biopsies by flow cytometry after administration in situ to the patient of a deoxyribonucleic acid thymidine tracer [2]. "This is difficult to determine in vivo." It is "the time which the cell population of tumor doubles if there is no cell loss" [3]. Tp (potential doubling time or cell doubling time after cell loss) is a little shorter than Tpot (measured before the tumour has received any cytotoxic treatment) [1].

Pretreatment Tpot measured in human tumor biopsies [2].
Tumor	Median (days)	Range (days)
Larynx	4	2-19
Tongue	4-6	2-16
Mouth, cheek	3.4	2-15
Esophagus	5	2.5-20
Cervix	5	3-20
Rectum	5	3-18
Prostate	42	15-70
Breast	14	3-70

Bibliographic references:

[1] Fowler, JF. 21 years of Biologically Effective Dose. Br J Radiol. 2010 Jul; 83(991): 554–568. Available at: http://dx.doi.org/10.1259%2Fbjr%2F31372149.

[2] Fowler JF. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol. 2005;44(3):265-76. Available at: http://dx.doi.org/10.1080/02841860410002824.
[3] The timely delivery of radical radiotherapy: standards and guidelines for the management of unscheduled treatment interruptions. (2008). 3rd ed. London, United Kingdom: Board of Faculty of Clinical Oncology, The Royal College of Radiologists. Available at: https://www.rcr.ac.uk/sites/default/files/publication/BFCO(08)6_Interruptions.pdf [Accessed 17 Jul. 2016].

K value or K factor

It is “the BED [biologically effective dose] equivalent of repopulation (in units of Gy/day)”, “the BED-equivalent repopulation factor” [1]. It is the "increase in dose required daily to obtain same biologic effect: recommended extra dose to add to total radiation dose for each day of prolongation, which can be given by increasing daily dose of remaining treatment". "Prolongation of overall treatment time due to unplanned interruptions during radiotherapy causes deleterious effect of accelerated repopulation of tumor clonogens. For the cancers of the head and neck, even a 1-day interruption resulted in a decrease in the local control rate by 1.4%" [9]. A “K value of 0.9 Gy/day represents the BED required each day (after Tdelay has been passed) to offset repopulation” [2]. It is “the biological dose per day required to compensate for on-going tumour cell repopulation. K is the BED equivalent of 1 days’ worth of repopulation” [3], “a factor used to determine the amount of radiation ‘wasted’ due to ongoing tumour repopulation” [4]. “If chemotherapy is able to completely inhibit repopulation then K=0 and would not be required” [1].
For head and neck treatments, it is “recommend K=0.1 Gy/day and Tdelay=0 in cases where the final overall times are less than 28 days” [1]. However, after this time, the K value is 0.5-0.7 Gy/day [9].

“There is at present very little data relating to K and Tdelay factors for other tumour types” [1].
“For cervix tumours, the time factors are probably around half those for head and neck tumours, i.e., 0.5 Gy/day” [1,5]. “For breast tumours, the K factors are likely to be around 0.3 Gy/day while for prostate tumours they are likely to be in the region 0.1–0.3 Gy/day, or even lower [1,6-8]”. “Little is known about the corresponding values of Tdelay” [1]. For transitional cell bladder carcinoma, K=0.36 Gy/day for a Tdelay=5-6 weeks [9]. For non-small cell lung cancer and a Tdaley>20 days, K=0.45 Gy/day [10,11]; but, for cases without mediastinal involvement, K=0.2 Gy/day [10].

Bibliographic references:

[1] Stamatakos, G. (2012). 2012 5th International Advanced Research Workshop on In Silico Oncology and Cancer Investigation (IARWISOCI). Piscataway, NJ: IEEE. Available at: http://www.5th-iarwisoci.iccs.ntua.gr/data/_uploaded/file/PROCEEDINGS_2012_5th_IARWISOCI_OPEN-ACCESS_VERSION_2012_DEC_05.pdf [Accessed 19 Jul. 2016].

[2] Dale RG, Hendry JH, Jones B, et al. Practical methods for compensating for missed treatment days in radiotherapy, with particularreference to head and neck schedules. Clin Oncol (R Coll Radiol). 2002 Oct;14(5):382-93. Available at: http://dx.doi.org/10.1053/clon.2002.0111.

[3] Dale RG, Jones B, Sinclair JA. Dose-equivalents of tumour repopulation during radiotherapy: the potential for confusion. Br J Radiol. 2000;73(872):892–894. Available at: http://dx.doi.org/10.1259/bjr.73.872.11026867.

[4] The timely delivery of radical radiotherapy: standards and guidelines for the management of unscheduled treatment interruptions. (2008). 3rd ed. London, United Kingdom: Board of Faculty of Clinical Oncology, The Royal College of Radiologists. Available at: https://www.rcr.ac.uk/sites/default/files/publication/BFCO(08)6_Interruptions.pdf [Accessed 17 Jul. 2016].

[5] Hendry JH, Bentzen SM, Dale RG, et al. A modelled comparison of the effect of using different ways to compensate for missed treatment days in radiotherapy. Clin Oncol. 1996;8(5):297–307. Available at: http://dx.doi.org/10.1016/s0936-6555(05)80715-0.

[6] Haustermans K, Fowler J, Geboes K, et al. Relationship between potential doubling time (Tpot), labelling index and duration of DNA synthesis in 60 oesophageal and 35 breast tumours: is it worthwhile to measure Tpot? Radiother Oncol. 1998;46(2):157–167. Available at: http://dx.doi.org/10.1016/s0167-8140(97)00164-3.

[7] Trott KR, Kummermehr J. What is known about tumour proliferation rates to choose between accelerated fractionation or hyperfractionation? Radiother Oncol. 1985;3(1):1–9. Available at: http://dx.doi.org/10.1016/s0167-8140(85)80002-5.

[8] King CR. What is the Tpot for prostate cancer? Radiobiological implications of the equivalent outcome with 125I or 103Pd. Int J Radiat Oncol Biol Phys. 2000;47(5):1165–1167. Available at: http://dx.doi.org/10.1016/s0360-3016(00)00543-5.
[9] Bese NS, Hendry J, Jeremic B. Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):654-61. Available at: http://dx.doi.org/10.1016/j.ijrobp.2007.03.010.
[10] Koukourakis M, Hlouverakis G, Kosma L, et al. The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys. 1996 Jan 15;34(2):315-22. Available at: http://dx.doi.org/10.1016/0360-3016(95)02102-7.
[11] Chen M, Jiang GL, Fu XL, et al. The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer. Lung Cancer. 2000 Apr;28(1):11-9. Available at: http://dx.doi.org/10.1016/S0169-5002(99)00113-0.

Tp (potential doubling time or cell doubling time after cell loss)

Tp is the potential doubling time of tumors [1]. It is the constant repopulation rate, i.e., a constant cell doubling time up to the end of the radiation treatment [2]. It is is the average doubling time of the clonogenic cells in days [3]. For example, in head and neck tumours or cervix cancer, it can be as short as 2 days; therefore one loses up to 1 Gy worth of cell killing when prolonging the course of radiotherapy. Tp it the fastest time in which a tumour can double its volume and depends on cell type and can be of the order of 2 days in fast growing tumours [1]. This "volume doubling time is determined by cell cycle time, growth factor, and rate of cell loss." Tumours such as squamous cel carcinomas have a relatively short volume doubling time; adenocarcinomas have a longer volume doubling time [4]. It can be measured in cell biology experiments (that requires optimal conditions for the tumour and is a worst case scenario) [1].
Patients on treatment should be prioritised according to the volume doubling time. The prolongation of overall treatment time affects treatment outcome or local tumour control in patients with tumours with short Tp [4].
In patients with muscle-invasive transitional cell bladder carcinoma, the clonogen doubling time is about 5–8 days [5].

Bibliographic references:

[1] IAEA Training Material on Radiation Protection in Radiotherapy - Radiation Protection in Radiotherapy - Part 3 - Biological Effects - Lecture 2: High Doses in Radiation Therapy. (2013). [Lectures/Slides]. Vienna, Austria: International Atomic Energy Agency. Available at: https://rpop.iaea.org/RPOP/RPoP/Content/Documents/TrainingRadiotherapy/Lectures/RT03_RadBiol2_RT_WEB.ppt [Accessed 12 Jul. 2016].

[2] Fowler, JF. 21 years of Biologically Effective Dose. Br J Radiol. 2010 Jul; 83(991): 554–568. Availavle at: http://dx.doi.org/10.1259%2Fbjr%2F31372149.

[3]  Tomé WA, Fowler JF. On the inclusion of proliferation in tumour control probability calculations for inhomogeneously irradiated tumours. Phys Med Biol. 2003 Sep 21;48(18):N261-8. Available at: http://dx.doi.org/10.1088/0031-9155/48/18/402.
[4] The timely delivery of radical radiotherapy: standards and guidelines for the management of unscheduled treatment interruptions. (2008). 3rd ed. London, United Kingdom: Board of Faculty of Clinical Oncology, The Royal College of Radiologists. Available at: https://www.rcr.ac.uk/sites/default/files/publication/BFCO(08)6_Interruptions.pdf [Accessed 17 Jul. 2016].
[5] Bese NS, Hendry J, Jeremic B. Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):654-61. Available at: http://dx.doi.org/10.1016/j.ijrobp.2007.03.010.

Tk (kick-off time or onset time) or Tdelay or Tdel

T_k, T_delay [1], or T_del [2] "represents any delay in the start of tumour cell repopulation in response to radiation treatment after radiation treatment has started." Repopulation of tumour cells due to radiation treatment starts after a passed lag period of T_k treatment days [3]. The repopulation time of tumour cells appears to vary during radiotherapy; at the commencement it may be slow (e.g., due to hypoxia); however, a certain time after the first fraction of radiotherapy (kick-off time), repopulation accelerates [4]. T_k is "the apparent starting time of rapid compensatory repopulation in tumor or tissue after the start of treatment, when it is assumed that there are just two rates of cell proliferation during radiotherapy: zero from start to T_k, then constant doubling each T_p days [cell doubling time] until end of treatment at T days [overall treatment time]" [5].

T_k could be between 21 and 32 days in human head and neck tumors [6,7] and non-small-cell lung cancer, and unlikely may be shorter, but may be longer in prostate cancer [8]. Fowler et al. [9] considered that prostate cancer would have a T_K value up to 10 times the T_K for head and neck tumors, approximately between 210 and 300 days, and Leborgne et al. [10] considered a T_K for prostate cancer of 52 days. Values for adenocarcinoma of the anus have not been defined [11].

Bibliographic references:
[1] The timely delivery of radical radiotherapy: standards and guidelines for the management of unscheduled treatment interruptions. (2008). 3rd ed. London, United Kingdom: Board of Faculty of Clinical Oncology, The Royal College of Radiologists. Available at: https://www.rcr.ac.uk/sites/default/files/publication/BFCO(08)6_Interruptions.pdf [Accessed 17 Jul. 2016].
[2] Wyatt RM, Beddoe AH, Dale RG. The effects of delays in radiotherapy treatment on tumour control. Phys Med Biol. 2003 Jan 21;48(2):139-55. Available at: http://dx.doi.org/10.1088/0031-9155/48/2/301.

[3] Tomé WA, Fowler JF. On the inclusion of proliferation in tumour control probability calculations for inhomogeneously irradiated tumours. Phys Med Biol. 2003 Sep 21;48(18):N261-8. Available at: http://dx.doi.org/10.1088/0031-9155/48/18/402.

[4] IAEA Training Material on Radiation Protection in Radiotherapy - Radiation Protection in Radiotherapy - Part 3 - Biological Effects - Lecture 2: High Doses in Radiation Therapy. (2013). [Lectures/Slides]. Vienna, Austria: International Atomic Energy Agency. Available at: https://rpop.iaea.org/RPOP/RPoP/Content/Documents/TrainingRadiotherapy/Lectures/RT03_RadBiol2_RT_WEB.ppt [Accessed 12 Jul. 2016].

[5] 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.

[6] Brenner, DJ.  Accelerated repopulation during radiotherapy.  Quantitative evidence for delayed onset. Radiat Oncol Invest. 1993;1(3):167–72. Available at: http://dx.doi.org/10.1002/roi.2970010306.

[7] Roberts, SA, Hendry, JH.  Time factors in larynx tumor radiotherapy: lag times and intertumor heterogeneity in clinical datasets from four centers. Int J Radiat Oncol Biol Phys. 1999;45(5):1247–57. Available at: http://dx.doi.org/10.1016/s0360-3016(99)00320-x.
[8] Fowler JF. Development of radiobiology for oncology—a personal view. Phys Med Biol. 2006 Jul 7;51(13):R263-86. Available at: http://dx.doi.org/10.1088/0031-9155/51/13/R16.
[9] Fowler, JF, Ritter, MA, Fenwick , JD, Chappell, RJ. How low is the alpha/beta ratio for prostate cancer? In regard to Wang et al., IJROBP 2003;55:194-203, Int J Radiat Oncol Biol Phys. 2003;57(2):593–5. Available at: http://dx.doi.org/10.1016/s0360-3016(03)00364-x.

[10] Leborgne, F, Fowler, J, Leborgne, JH, Mezzera, J. Later outcomes and alpha/beta estimate from hypofractionated conformal threediomensional radiotherapy versus standard fractionation for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82(3):1200–7. Available at: http://dx.doi.org/10.1016/j.ijrobp.2010.12.040.
[11] Joon DL, Chao MW, Ngan SY, Joon ML, Guiney MJ. Primary adenocarcinoma of the anus: a retrospective analysis. Int J Radiat Oncol Biol Phys. 1999 Dec 1;45(5):1199-205. Available at: http://dx.doi.org/10.1016/S0360-3016(99)00267-9.

Choi-Baisi classification for bronchoscopic findings in esophageal cancer

This classification allows to identify bronchoscopic findings that predict resectability of esophageal carcinoma [1-3].

Category I: No abnormalities [2].

Category II: Impingement and no mucosal changes [2].

Category IIa: "(...) slight compression on the posterior wall of the trachea or left bronchus and no tumorous infiltration of the tracheobronchial tree; normal mobility of the tracheobronchial wall; and parallel and regular longitudinal folds of the pars membranacea. (...) This group of patients can be identified because the compression on the involved tracheobronchial tree is usually slight and its mobility is normal. (...) The tracheobronchial tree is only compressed and not infiltrated by the tumor, thus making a radical resection possible" [1].

Category IIb: "(...) compression in which the fixation of the tracheobronchial tree suggests tumorous invasion; impingement or deviation of the trachea or left bronchus or widening of the carina, with or without narrowing, associated with a reduction in mobility during breathing and coughing (ie, fixation of the involved tracheobronchial segment). The mucosa is still normal, but the longitudinal folds of the pars membranacea may be widened. (...) There is a frank infiltration of the tracheobronchial tree and a radical resection is unlikely. These patients can be downstaged by appropriate neoadjuvant" treatment "that would then make radical resection feasible" [1].

Category III: Mucosal invasion [2]/irregularities or tracheoesophageal fistula [3].

Bibliographic references:

[1] Baisi A, Bonavina L, Peracchia A. Bronchoscopic staging of squamous cell carcinoma of the upper thoracic esophagus. Arch Surg. 1999;134(2):140-143. Available at: http://dx.doi.org/10.1001/archsurg.134.2.140.

[2] Choi  TKSiu  FSLam  KWong  J Bronchoscopy and carcinoma of the esophagus, I: findings of bronchoscopy in carcinoma of the esophagus. Am J Surg. 1984;147(6):757-759. Available at: http://dx.doi.org/10.1016/0002-9610(84)90194-6.

[3] Choi  TKSiu  FSLam  KWong  J Bronchoscopy and carcinoma of the esophagus, II: carcinoma of the esophagus with tracheobronchial involvement. Am J Surg. 1984;147(6):760-762. Available at: http://dx.doi.org/10.1016/0002-9610(84)90195-8.

Efficacy

It "is the extent to which a specific intervention, procedure, or service produces the desired effect, under ideal conditions (controlled environment, laboratory circumstances)." Efficacy is equal to effectiveness; only circumstances change. For example, "the efficacy of vaccine A was achieved under ideal laboratory circumstances, yet, its effectiveness needs to be shown."

Bibliographic references: Hayajneh.org. (n.d.). Effectiveness, Efficiency, and Efficacy : Definition - Health Care and Health Care Informatics Terms - Define Efficiency, Effectiveness, and Efficacy. [online] Available at: http://www.hayajneh.org/glossary/vocabulary/e/EfficiencyEffectivenessEfficacy.html [Accessed 2 Jul. 2016].

Efficiency

It "is the ratio of the output to the inputs of any system. An efficient system or person is one who achieves higher levels of performance (outcome, output) relative to the inputs (resources, time, money) consumed."

Bibliographic reference: Hayajneh.org. (n.d.). Effectiveness, Efficiency, and Efficacy : Definition - Health Care and Health Care Informatics Terms - Define Efficiency, Effectiveness, and Efficacy. [online] Available at: http://www.hayajneh.org/glossary/vocabulary/e/EfficiencyEffectivenessEfficacy.html [Accessed 2 Jul. 2016].

Effectiveness

It "is the extent to which planned outcomes, goals, or objectives are achieved as a result of an activity, strategy, intervention or initiative intended to achieve the desired effect, under ordinary circumstances (not controlled circumstances such as in laboratory)." For example, "a vaccine is effective when it is capable to produce the desired effect (protection against disease) in the population, under ordinary circumstances. Being effective means achieving organizational goals. Being efficient means achieving goals with little wasted resources. Effectiveness comes first."

Bibliographic reference: Hayajneh.org. (n.d.). Effectiveness, Efficiency, and Efficacy : Definition - Health Care and Health Care Informatics Terms - Define Efficiency, Effectiveness, and Efficacy. [online] Available at: http://www.hayajneh.org/glossary/vocabulary/e/EfficiencyEffectivenessEfficacy.html [Accessed 2 Jul. 2016].

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].