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].