Early clinical and radiological pulmonary complications following breast cancer radiation therapy:...
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Early clinical and radiological pulmonary complications following breast cancer radiation therapy: NTCP fit with four different models Rancati T, Wennberg B, Lind P, et al (Natl Cancer Inst, Milan, Italy; Karolinska Univ Hosp, Stockholm; Karolinska Inst, Stockholm) Radiother Oncol 82:308-316, 2007 Objective.—To fit four different NTCP (Normal Tissue Complication Probability) models to prospectively col- lected data on short-term pulmonary com- plications following breast cancer radio- therapy (RT). Materials/Methods.—Four hundred and seventy-five breast cancer patients, referred to the Radiotherapy Department at Stockholm Söder Hospital (1994-1998) for adjuvant post-operative RT were prospectively followed for pulmonary complications 1, 4, and 7 months after the completion of RT. Eighty-seven patients with complete dose-volume histogram (DVH) of the ipsilateral lung were select- ed for the present analysis. Mean dose to the ipsilateral lateral lung ranged from 2.5 to 18 Gy (median 12 Gy). Three different endpoints were considered: (1) clinical pneumonitis scored according to CTC- NCIC criteria: asymptomatic (grade 0) vs grade 1 and grade 2; (2) radiological changes assessed with diagnostic chest X-ray: no/slight radiological changes vs moderate/severe; (3) radiological changes assessed with CT: no/slight vs moder- ate/severe. Four NTCP models were used: the Lyman model with DVH reduced to the equivalent uniform dose (LEUD), the Logit model with DVH reduced to EUD, the Mean Lung Dose (MLD) model and the Relative Seriality (RS) model. The data fitting procedure was done using the maximum likelihood analysis. The analy- sis was done on the entire population (n = 87) and on a subgroup of patients treated with loco-regional RT (n = 44). Results.—24/87 patients (28%) de- veloped clinical pneumonitis; 28/81 pa- tients (35%) had radiological side effects on chest X-rays and 11/75 patients (15%) showed radiological density changes on Computed Tomography (CT). The analysis showed that the risk of clinical pneumonitis was a smooth function of EUD (calculated from DVH using n = 0.86±0.10, best fit result). With LEUD, the relationship between EUD and NTCP could be described with a D 50 of 16.4Gy±1.1Gy and a steepness parameter m of 0.36±0.7. The results found in the overall population were substantially con- firmed in the subgroup of patients treated with loco-regional RT. Conclusions.—A large group of prospective patient data (87 pts), includ- ing grade 1 pneumonitis, were analysed. The four NTCP models fit quite accurate- ly the considered endpoints. EUD or the mean lung dose are robust and simple parameters correlated with the risk of pneumonitis. For all endpoints the D 50 values ranged in an interval between 10 and 20 Gy. This is a well-done prospective clinical study of the dosimetric param- eters predictive of radiation therapy- induced lung injury in patients irradi- ated for breast cancer. The strengths of the study are its prospective design and its use of objective quantitative end points. The data basically demonstrate that the assessment of the incidence of radiation therapy–induced lung injury is extremely dependent on the study end point used: symptoms versus ra- diographs. Typically, radiologic changes in diagnostic imaging can be seen in a far larger fraction of patients than in those who develop severe pul- monary symptoms. This study demonstrated that the in- cidence of pulmonary symptoms can be related to simple dosimetric parameters, such as the mean lung dose. The authors combined mild and moderate sympto- matic events (those not requiring and those requiring steroids, respectively). In practice, the more severe symptoms are much more clinically troubling than are minor complaints not requiring inter- vention. It would have been helpful for the authors to provide dosimetric predic- tors of the more severe clinical end points (ie, those requiring steroids). Further, it is often cumbersome to apply such models in the busy clinical setting. Therefore, relating the incidence of symptoms to simple clinical measures (eg, the height of the lung shadow seen on tangent photon fields) would also be very useful. The authors should be congratulat- ed on this nicely done study. Additional research is needed to better define the dosimetric and clinical parameters asso- ciated with radiation-induced lung in- jury in patients irradiated for breast cancer. L. B. Marks, MD 74 Breast Diseases: A Year Book ® Quarterly 74 Vol 19 No 1 2008
Transcript of Early clinical and radiological pulmonary complications following breast cancer radiation therapy:...
Early clinical and radiologicalpulmonary complicationsfollowing breast cancerradiation therapy: NTCP fit withfour different models Rancati T, Wennberg B, Lind P, et al (NatlCancer Inst, Milan, Italy; Karolinska UnivHosp, Stockholm; Karolinska Inst,Stockholm)
Radiother Oncol 82:308-316, 2007
Objective.—To fit four differentNTCP (Normal Tissue ComplicationProbability) models to prospectively col-lected data on short-term pulmonary com-plications following breast cancer radio-therapy (RT).
Materials/Methods.—Four hundredand seventy-five breast cancer patients,referred to the Radiotherapy Departmentat Stockholm Söder Hospital (1994-1998)for adjuvant post-operative RT wereprospectively followed for pulmonarycomplications 1, 4, and 7 months after thecompletion of RT. Eighty-seven patientswith complete dose-volume histogram(DVH) of the ipsilateral lung were select-ed for the present analysis. Mean dose tothe ipsilateral lateral lung ranged from 2.5to 18 Gy (median 12 Gy). Three differentendpoints were considered: (1) clinicalpneumonitis scored according to CTC-NCIC criteria: asymptomatic (grade 0) vsgrade 1 and grade 2; (2) radiologicalchanges assessed with diagnostic chest X-ray: no/slight radiological changes vsmoderate/severe; (3) radiological changesassessed with CT: no/slight vs moder-ate/severe. Four NTCP models were used:the Lyman model with DVH reduced tothe equivalent uniform dose (LEUD), the
Logit model with DVH reduced to EUD,the Mean Lung Dose (MLD) model andthe Relative Seriality (RS) model. Thedata fitting procedure was done using themaximum likelihood analysis. The analy-sis was done on the entire population (n = 87) and on a subgroup of patientstreated with loco-regional RT (n = 44).
Results.—24/87 patients (28%) de-veloped clinical pneumonitis; 28/81 pa-tients (35%) had radiological side effectson chest X-rays and 11/75 patients (15%)showed radiological density changes on Computed Tomography (CT). Theanalysis showed that the risk of clinicalpneumonitis was a smooth function ofEUD (calculated from DVH using n =0.86±0.10, best fit result). With LEUD,the relationship between EUD and NTCPcould be described with a D50 of16.4Gy±1.1Gy and a steepness parameterm of 0.36±0.7. The results found in theoverall population were substantially con-firmed in the subgroup of patients treatedwith loco-regional RT.
Conclusions.—A large group ofprospective patient data (87 pts), includ-ing grade 1 pneumonitis, were analysed.The four NTCP models fit quite accurate-ly the considered endpoints. EUD or themean lung dose are robust and simple parameters correlated with the risk ofpneumonitis. For all endpoints the D50
values ranged in an interval between 10and 20 Gy.
This is a well-done prospectiveclinical study of the dosimetric param-eters predictive of radiation therapy-induced lung injury in patients irradi-ated for breast cancer. The strengths ofthe study are its prospective design and
its use of objective quantitative endpoints. The data basically demonstratethat the assessment of the incidence ofradiation therapy–induced lung injuryis extremely dependent on the studyend point used: symptoms versus ra-diographs. Typically, radiologicchanges in diagnostic imaging can beseen in a far larger fraction of patientsthan in those who develop severe pul-monary symptoms.
This study demonstrated that the in-cidence of pulmonary symptoms can berelated to simple dosimetric parameters,such as the mean lung dose. The authorscombined mild and moderate sympto-matic events (those not requiring andthose requiring steroids, respectively). Inpractice, the more severe symptoms aremuch more clinically troubling than areminor complaints not requiring inter-vention. It would have been helpful forthe authors to provide dosimetric predic-tors of the more severe clinical endpoints (ie, those requiring steroids).Further, it is often cumbersome to applysuch models in the busy clinical setting.Therefore, relating the incidence ofsymptoms to simple clinical measures(eg, the height of the lung shadow seenon tangent photon fields) would also bevery useful.
The authors should be congratulat-ed on this nicely done study. Additionalresearch is needed to better define thedosimetric and clinical parameters asso-ciated with radiation-induced lung in-jury in patients irradiated for breastcancer.
L. B. Marks, MD
74 Breast Diseases: A Year Book®
Quarterly74 Vol 19 No 1 2008
