- Email: [email protected]
In Reply to Williams
International Journal of
Radiation Oncology biology
physics
www.redjournal.org
COMMENTS Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: A prospective study with 7-year follow-up In Regard to Jae´n et al To the Editor: I was astonished to see that results presented by Jae´n et al (1) were expressed as means without associated measures of dispersion (eg, standard deviations), particularly as such information is readily available from the statistical analysis software the authors used (SPSS). I do not doubt that the authors carried out the analyses correctly, but believe this omission needs correction to allow the reader to assess the data more critically. Norman R. Williams, PhD Clinical Trials Group UCL Division of Surgery and Interventional Science Charles Bell House, Riding House Street London, UK http://dx.doi.org/10.1016/j.ijrobp.2013.08.041
Reference 1. Jae´n J, Va´zquez G, Alonso E, et al. Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: A prospective study with 7-year follow-up. Int J Radiat Oncol Biol Phys 2012;84: e565-e570.
In Reply to Williams To the Editor: The authors appreciate the comments regarding our article (1, 2). We agree that descriptive results of continuous variables are better expressed as means plus any dispersion measure, such as standard deviations (SDs) and mean differences by 95% confidence intervals (95% CIs) better than by only P values. The authors apologize for the omission of these data; we believed that the tables became more understandable in this simple format. In any case, the reader can find this information here: Mean (SD) baseline spirometric values: forced vital capacity (FVC) 86.3% (11.7%), forced expiratory volume in 1 second
Int J Radiation Oncol Biol Phys, Vol. 87, No. 5, pp. 857e860, 2013 0360-3016/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
(FEV1) 93.8% (13.9%), carbon monoxide diffusing capacity test (DLCO) 79.5% (13.8%), ventilation 49.5% (3.7%), perfusion 50.7% (6.5%). Mean (SD) lung doseevolume parameters: V10 Z 13.7% (9.1%), V20 Z 9.6% (5.8%), V30 Z 7.9% (4.9%), V40 Z 5.6% (3.8%), mean lung dose (MLD) Z 10.9 Gy (5.8 Gy), Kutcher & Burman equivalent uniform dose 6.7 Gy (3.2 Gy), Lyman & Woldbarst effective dose 11.1 Gy (5.4 Gy). Percentage differences (SD) at 7 years from the baseline PFT values: FVC þ8.3% (11.9%), FEV1 þ3.9% (8.6%), DLCO 1.6% (19.0%), ventilation 2.6% (6.7%), perfusion 3.0% (4.9%). Differences on pre-radiation therapy pulmonary function tests values for some patient characteristics: Age (<53 y vs >52 y): FVC 7.1% (95% CI: 0.3% to 14.4%); FEV1 5.5% (95% CI: 3.6% to 14.6%); DLCO 5.9% (95% CI: 3.6% to 15.5%); ventilation -1.0% (95% CI: 3.3% to 1.3%); perfusion -3.5% (95% CI: 7.5% to 0.5%). Chemotherapy (no vs yes): FVC 1.1% (95% CI: 8.9% to 6.7%); FEV1 2.2% (95% CI: 7.1% to 11.5%); DLCO 0.6% (95% CI: 9.2% to 10.3%); ventilation 0.2% (95% CI: 2.1% to 2.6%); perfusion 3.7% (95% CI: 0.3% to 7.7%). Smoking (no vs yes): FVC 1.0% (95% CI: 7.8% to 9.8%); FEV1 5.5% (95% CI: 4.9% to 15.9%); DLCO 6.4% (95% CI: 4.4% to 17.3%); ventilation 0.3% (95% CI: 2.9% to 2.4%); perfusion 1.3% (95% CI: 3.4% to 6.0%). Surgery (conservative vs mastectomy): FVC 8.1% (95% CI: 0.7% to 15.5%); FEV1 4.6% (95% CI: 4.7% to 13.9%); DLCO 6.3% (95% CI: 3.4% to 16.0%); ventilation 1.2% (95% CI: 1.2% to 3.6%); perfusion 0.4% (95% CI: 3.8% to 4.6%). Differences on mean lung dosedvolume parameters related to radiation fields (tangential vs tangential þ supraclavicular): V10Gy 11.3% (95% CI: 16.4% to 6.2%); V20Gy 7.0% (95% CI: 10.3% to 3.8%); V30Gy 5.7% (95% CI: -8.5% to 3.0%); V40Gy 4.4% (95% CI: 6.6% to 2.2%); mean lung dose 7.6 Gy (95% CI: 10.6 Gy to 4.5 Gy); Kutcher & Burman equivalent uniform dose 4.0 Gy (95% CI: 5.9 Gy to 2.2 Gy); Lyman & Woldbarst effective dose 7.4 Gy (95% CI: 10.3 Gy to 4.4 Gy).
Javier Jae´n, MD, PhD Unidad de Atencio´n Integral al Ca´ncer Hospital Universitario Puerta del Mar Ca´diz, Spain http://dx.doi.org/10.1016/j.ijrobp.2013.08.039
858
International Journal of Radiation Oncology Biology Physics
Comments
References 1. Jae´n J, Va´zquez G, Alonso E, et al. Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: a prospective study with 7-year follow-up. Int J Radiat Oncol Biol Phys 2012;84: e565-e570. 2. Wiliams N, et al. In regard to Jaen et al. Int J Radiat Oncol Biol Phys 2013;87:857.
Estimation of a self-consistent set of radiobiological parameters from hypofractionated versus standard radiation therapy of prostate cancer Fig. 1. Relation of Tk (days) as a function of d (Gy) for prostate cancer (black curve) and head-and-neck cancer (gray curve).
In Regard to Pedicini et al To the Editor: In recent years, many authors have researched the more appropriate value of the kickoff time (Tk) for accelerated cell repopulation during radiation therapy. Such a value may have a high impact on the optimal radiation therapy dose fractionation for any tumor. The standard approach was based on the hypothesis that Tk may be variable among tumors but fixed within the same tumor cell type. However, a different approach, based on the involvement of subpopulations of stem cells during radiation therapy, was recently introduced (1). This hypothesis has been guided by the evidence of similarity between the effective doubling times of different tumors (ie, head-and-neck and prostate) at the beginning of the accelerated proliferation. Such a similarity was explainable with a natural selection of more rapidly proliferating stem cells by radiation. In fact, normally in the more radioresistant G0 phase these cells are in the early stages of differentiation and when activated could have a very short doubling time independent of the selected tissue origin (because stem cells might have the same doubling time for prostate, head-and-neck, and breast). According to this hypothesis, the number of surviving cells for which the stem cells may have the signal of activation could be obtained by the linear quadratic model, as follows: NA ZN0 $e
mdðaþbdÞ
11 TK Z dða þ bdÞ
ð3Þ
Such a relationship would explain the differences in Tk among tumors (different a and b) and, at the same time, the possible differences within the same tumor type when groups of patients are treated with different schedules of radiation therapy (different d ). Figure 1 shows Tk as a function of dose per fraction, adopting a and b available in the literature for prostate (1) and head-and-neck (4) cancers, respectively. For a standard dose per fraction of 2 Gy, tumors with high a or low b (ie, head-and-neck) have a lower Tk (w14 days for head-and-neck vs w21 days for prostate). Moreover, for hypofractionated schedules (high dose per fraction) the accelerated proliferation starts early because of the stem cell activation with a lower number of fractions. Piernicola Pedicini, PhD Service of Medical Physics I.R.C.C.S. Regional Cancer Hospital Rionero-in-Vulture, Italy http://dx.doi.org/10.1016/j.ijrobp.2013.08.016
ð1Þ
where, NA indicates the number of activated stem cells, N0 the initial number of clonogens, d the dose/fraction, a and b the intrinsic and repair cell sensitivity respectively, and m the number of fractions corresponding to the stem cell activation. Therefore, when radiation therapy is delivered 5 days per week, rearranging equation 1, Tk could be obtained as 7lnðN0 =NA Þ TK Z ð2Þ 5dða þ bdÞ In this context, Withers (2) and Gao et al (3) have argued that the process of stem cell activation for accelerated proliferation could begin when the tumor population has decreased to the order of a few thousand cells, that is, when
References 1. Pedicini P, Strigari L, Benassi M. Estimation of a self-consistent set of radiobiological parameters from hypofractionated versus standard radiation therapy of prostate cancer. Int J Radiat Oncol Biol Phys 2013; 85:e231-e237. 2. Withers HR. Treatment-induced accelerated human tumor growth. Semin Radiat Oncol 1993;3:135-143. 3. Gao M, Mayr NA, Huang Z, et al. When tumor repopulation starts? The onset time of prostate cancer during radiation therapy. Acta Oncol 2010;49:1269-1275. 4. Fowler JF. Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling. Int J Radiat Oncol Biol Phys 2009;73:15321537.
Radiation Oncology biology
physics
www.redjournal.org
COMMENTS Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: A prospective study with 7-year follow-up In Regard to Jae´n et al To the Editor: I was astonished to see that results presented by Jae´n et al (1) were expressed as means without associated measures of dispersion (eg, standard deviations), particularly as such information is readily available from the statistical analysis software the authors used (SPSS). I do not doubt that the authors carried out the analyses correctly, but believe this omission needs correction to allow the reader to assess the data more critically. Norman R. Williams, PhD Clinical Trials Group UCL Division of Surgery and Interventional Science Charles Bell House, Riding House Street London, UK http://dx.doi.org/10.1016/j.ijrobp.2013.08.041
Reference 1. Jae´n J, Va´zquez G, Alonso E, et al. Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: A prospective study with 7-year follow-up. Int J Radiat Oncol Biol Phys 2012;84: e565-e570.
In Reply to Williams To the Editor: The authors appreciate the comments regarding our article (1, 2). We agree that descriptive results of continuous variables are better expressed as means plus any dispersion measure, such as standard deviations (SDs) and mean differences by 95% confidence intervals (95% CIs) better than by only P values. The authors apologize for the omission of these data; we believed that the tables became more understandable in this simple format. In any case, the reader can find this information here: Mean (SD) baseline spirometric values: forced vital capacity (FVC) 86.3% (11.7%), forced expiratory volume in 1 second
Int J Radiation Oncol Biol Phys, Vol. 87, No. 5, pp. 857e860, 2013 0360-3016/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
(FEV1) 93.8% (13.9%), carbon monoxide diffusing capacity test (DLCO) 79.5% (13.8%), ventilation 49.5% (3.7%), perfusion 50.7% (6.5%). Mean (SD) lung doseevolume parameters: V10 Z 13.7% (9.1%), V20 Z 9.6% (5.8%), V30 Z 7.9% (4.9%), V40 Z 5.6% (3.8%), mean lung dose (MLD) Z 10.9 Gy (5.8 Gy), Kutcher & Burman equivalent uniform dose 6.7 Gy (3.2 Gy), Lyman & Woldbarst effective dose 11.1 Gy (5.4 Gy). Percentage differences (SD) at 7 years from the baseline PFT values: FVC þ8.3% (11.9%), FEV1 þ3.9% (8.6%), DLCO 1.6% (19.0%), ventilation 2.6% (6.7%), perfusion 3.0% (4.9%). Differences on pre-radiation therapy pulmonary function tests values for some patient characteristics: Age (<53 y vs >52 y): FVC 7.1% (95% CI: 0.3% to 14.4%); FEV1 5.5% (95% CI: 3.6% to 14.6%); DLCO 5.9% (95% CI: 3.6% to 15.5%); ventilation -1.0% (95% CI: 3.3% to 1.3%); perfusion -3.5% (95% CI: 7.5% to 0.5%). Chemotherapy (no vs yes): FVC 1.1% (95% CI: 8.9% to 6.7%); FEV1 2.2% (95% CI: 7.1% to 11.5%); DLCO 0.6% (95% CI: 9.2% to 10.3%); ventilation 0.2% (95% CI: 2.1% to 2.6%); perfusion 3.7% (95% CI: 0.3% to 7.7%). Smoking (no vs yes): FVC 1.0% (95% CI: 7.8% to 9.8%); FEV1 5.5% (95% CI: 4.9% to 15.9%); DLCO 6.4% (95% CI: 4.4% to 17.3%); ventilation 0.3% (95% CI: 2.9% to 2.4%); perfusion 1.3% (95% CI: 3.4% to 6.0%). Surgery (conservative vs mastectomy): FVC 8.1% (95% CI: 0.7% to 15.5%); FEV1 4.6% (95% CI: 4.7% to 13.9%); DLCO 6.3% (95% CI: 3.4% to 16.0%); ventilation 1.2% (95% CI: 1.2% to 3.6%); perfusion 0.4% (95% CI: 3.8% to 4.6%). Differences on mean lung dosedvolume parameters related to radiation fields (tangential vs tangential þ supraclavicular): V10Gy 11.3% (95% CI: 16.4% to 6.2%); V20Gy 7.0% (95% CI: 10.3% to 3.8%); V30Gy 5.7% (95% CI: -8.5% to 3.0%); V40Gy 4.4% (95% CI: 6.6% to 2.2%); mean lung dose 7.6 Gy (95% CI: 10.6 Gy to 4.5 Gy); Kutcher & Burman equivalent uniform dose 4.0 Gy (95% CI: 5.9 Gy to 2.2 Gy); Lyman & Woldbarst effective dose 7.4 Gy (95% CI: 10.3 Gy to 4.4 Gy).
Javier Jae´n, MD, PhD Unidad de Atencio´n Integral al Ca´ncer Hospital Universitario Puerta del Mar Ca´diz, Spain http://dx.doi.org/10.1016/j.ijrobp.2013.08.039
858
International Journal of Radiation Oncology Biology Physics
Comments
References 1. Jae´n J, Va´zquez G, Alonso E, et al. Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: a prospective study with 7-year follow-up. Int J Radiat Oncol Biol Phys 2012;84: e565-e570. 2. Wiliams N, et al. In regard to Jaen et al. Int J Radiat Oncol Biol Phys 2013;87:857.
Estimation of a self-consistent set of radiobiological parameters from hypofractionated versus standard radiation therapy of prostate cancer Fig. 1. Relation of Tk (days) as a function of d (Gy) for prostate cancer (black curve) and head-and-neck cancer (gray curve).
In Regard to Pedicini et al To the Editor: In recent years, many authors have researched the more appropriate value of the kickoff time (Tk) for accelerated cell repopulation during radiation therapy. Such a value may have a high impact on the optimal radiation therapy dose fractionation for any tumor. The standard approach was based on the hypothesis that Tk may be variable among tumors but fixed within the same tumor cell type. However, a different approach, based on the involvement of subpopulations of stem cells during radiation therapy, was recently introduced (1). This hypothesis has been guided by the evidence of similarity between the effective doubling times of different tumors (ie, head-and-neck and prostate) at the beginning of the accelerated proliferation. Such a similarity was explainable with a natural selection of more rapidly proliferating stem cells by radiation. In fact, normally in the more radioresistant G0 phase these cells are in the early stages of differentiation and when activated could have a very short doubling time independent of the selected tissue origin (because stem cells might have the same doubling time for prostate, head-and-neck, and breast). According to this hypothesis, the number of surviving cells for which the stem cells may have the signal of activation could be obtained by the linear quadratic model, as follows: NA ZN0 $e
mdðaþbdÞ
11 TK Z dða þ bdÞ
ð3Þ
Such a relationship would explain the differences in Tk among tumors (different a and b) and, at the same time, the possible differences within the same tumor type when groups of patients are treated with different schedules of radiation therapy (different d ). Figure 1 shows Tk as a function of dose per fraction, adopting a and b available in the literature for prostate (1) and head-and-neck (4) cancers, respectively. For a standard dose per fraction of 2 Gy, tumors with high a or low b (ie, head-and-neck) have a lower Tk (w14 days for head-and-neck vs w21 days for prostate). Moreover, for hypofractionated schedules (high dose per fraction) the accelerated proliferation starts early because of the stem cell activation with a lower number of fractions. Piernicola Pedicini, PhD Service of Medical Physics I.R.C.C.S. Regional Cancer Hospital Rionero-in-Vulture, Italy http://dx.doi.org/10.1016/j.ijrobp.2013.08.016
ð1Þ
where, NA indicates the number of activated stem cells, N0 the initial number of clonogens, d the dose/fraction, a and b the intrinsic and repair cell sensitivity respectively, and m the number of fractions corresponding to the stem cell activation. Therefore, when radiation therapy is delivered 5 days per week, rearranging equation 1, Tk could be obtained as 7lnðN0 =NA Þ TK Z ð2Þ 5dða þ bdÞ In this context, Withers (2) and Gao et al (3) have argued that the process of stem cell activation for accelerated proliferation could begin when the tumor population has decreased to the order of a few thousand cells, that is, when
References 1. Pedicini P, Strigari L, Benassi M. Estimation of a self-consistent set of radiobiological parameters from hypofractionated versus standard radiation therapy of prostate cancer. Int J Radiat Oncol Biol Phys 2013; 85:e231-e237. 2. Withers HR. Treatment-induced accelerated human tumor growth. Semin Radiat Oncol 1993;3:135-143. 3. Gao M, Mayr NA, Huang Z, et al. When tumor repopulation starts? The onset time of prostate cancer during radiation therapy. Acta Oncol 2010;49:1269-1275. 4. Fowler JF. Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling. Int J Radiat Oncol Biol Phys 2009;73:15321537.