|Year : 2019 | Volume
| Issue : 5 | Page : 999-1004
Conformal electron beam radiotherapy using custom-made step bolus for postmastectomy chest wall irradiation: An institutional experience
Balasubramanian Ananthi1, Kunjithapatham Bhuvana2, Rangad Viswanathan Faith1, Ganesarajah Selvaluxmy1, Nagarajan Vivekanandan2, Iyer Priya1
1 Department of Radiation Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
2 Department of Medical Physics, Cancer Institute (WIA), Chennai, Tamil Nadu, India
|Date of Web Publication||4-Oct-2019|
Department of Radiation Oncology, Cancer Institute (WIA), #38 Sardar Patel Road, Chennai - 600 036, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Postmastectomy radiation (PMRT) to the chest wall using electron beam treatment with uniform bolus was practiced at our institution. The planning target volume (PTV) included the chest wall and the internal mammary nodes (IMN) along with supraclavicular nodal regions. The varying thickness of the postmastectomy chest wall and the varying position of the IMN resulted in dose inhomogeneity in the PTV. In addition, there was the risk of increased lung and cardiac doses. In this prospective study, we report the making of a custom-made bolus using dental wax called “step bolus.”
Materials and Methods: From March 2010 to January 2011, 167 patients received PMRT. As conformal photon plans were not acceptable in 48 patients, they were treated with single energy electrons and custom-made bolus.
Results: Addition of the step bolus improved dose distribution to the PTV reduced the mean lung dose %, the mean heart dose % and lung dose (D10, D20, D30, D50, and D70). Forty-seven patients had Grade 2, and one patient had Grade 3 skin toxicity. Acute symptomatic radiation pneumonitis was observed in one patient. At 5 years, 29 patients were alive with a median follow-up of 32 months and no local recurrences were observed. One patient died of myocardial infarction unrelated to treatment, one patient did not come for follow-up, 22 patients had systemic metastases, and 24 patients were disease free.
Conclusion: A custom-made step bolus using dental wax can be used for tissue compensation in electron beam therapy with resulting good local disease control and acceptable toxicity.
Keywords: Bolus, conformal radiotherapy, dental wax, electron beam therapy, postmastectomy radiation
|How to cite this article:|
Ananthi B, Bhuvana K, Faith RV, Selvaluxmy G, Vivekanandan N, Priya I. Conformal electron beam radiotherapy using custom-made step bolus for postmastectomy chest wall irradiation: An institutional experience. J Can Res Ther 2019;15:999
|How to cite this URL:|
Ananthi B, Bhuvana K, Faith RV, Selvaluxmy G, Vivekanandan N, Priya I. Conformal electron beam radiotherapy using custom-made step bolus for postmastectomy chest wall irradiation: An institutional experience. J Can Res Ther [serial online] 2019 [cited 2020 Jan 23];15:999. Available from: http://www.cancerjournal.net/text.asp?2019/15/5/999/244472
| > Introduction|| |
Randomized trials in high-risk patients have shown that there is the advantage of increased survival in those who receive postmastectomy radiation (PMRT).,,, Whenever postmastectomy irradiation was considered, according to the National Comprehensive Cancer Network guidelines and existing evidence, the recommendation was to consider radiation to internal mammary nodal regions along with chest wall irradiation including the supraclavicular (SCL) regions., Recent studies on early breast cancer have shown that irradiation of the regional nodes including internal mammary nodal regions had a marginal effect on overall survival. In addition, a reduction in breast cancer mortality and an improvement in the disease-free survival and distant disease-free survival is reported.,
PMRT using electrons for chest wall radiotherapy (CWRT) had been practiced at the Institute for the last 25 years. Previously, the thickness of the chest wall was assessed with a lateral chest radiograph or ultrasound. The electron energy required was selected using depth dose tables. Depending on the energy of the electron beam selected, the thickness of commercially available gel sheet bolus of uniform thickness was chosen, to try and achieve uniform distribution of dose from the skin surface to the rib-pleura interface. Since 2009, we started computed tomography (CT)-based conformal radiotherapy for PMRT. The region of the internal mammary nodes (IMN) was included with the chest wall target volume and these along with SCL nodal regions were considered as part of locoregional treatment. Axillary radiation was considered only if axillary clearance was not achieved. As a routine axillary nodal irradiation was not considered whenever axillary dissection was complete.,,, Conformal radiotherapy with photons using multiple-shaped fields, field in field technique or with wedges for intensity modulation, yields good dose distributions in most of the patients. However, in patients with long horizontal scars and certain body build, acceptable dose distribution to the target and the organs at risk (OAR) i.e., ipsilateral lung and heart may not be achieved with conformal photon fields. The physical nature of electrons results in an abrupt fall off of dose and controllable depth of penetration.,, Electron treatment was expected to achieve better dose distribution for CWRT., With CT-based three-dimensional (3D) computer planning, the nonuniform thickness of the postmastectomy chest wall and the variable position of the internal mammary vessels, which are used as surrogate for the IMN, became obvious. Dose distribution to the target, the heart and lungs, was shown to be different from that extrapolated using the Isodose charts. This prompted us to consider dose modulation using a custom-made step bolus using dental wax.
| > Materials and Methods|| |
From March 2010 to January 2011, 167 patients with node-positive early-stage breast cancer and Stage 3 disease required PMRT which included radiotherapy to the chest wall, SCL, and internal mammary nodal regions. Irradiation to the axilla was also included in one patient who did not have surgical axillary clearance.,,, From this group, 48 patients were included for this prospective nonrandomized study. These were the patients in whom conformal photon beam radiotherapy plans was not acceptable due to dose inhomogeneity to the planning target volume (PTV) or high dose to the heart or lungs or both. The number of patients having left- and right-sided disease was 24 each. There are no exclusion criteria as this technique was done in those patients requiring postmastectomy irradiation in whom conformal photon beam radiotherapy was not satisfactory.
With the patient in the treatment position on the breast board, a thermoplastic mould was made. Three fiducial setup markers were placed. The superior, inferior, medial, and lateral borders of the chest wall fields were marked and radio-opaque markers were placed. Planning CT scans were taken with 5-mm slice thickness. As per the Radiation Therapy Oncology Group (RTOG) contouring guidelines, the PTV was generated after delineating the clinical target volume of the chest wall and the IMN which was delineated using the internal mammary vessels as surrogate. SCL fields were added for all patients, and in one patient, the axilla was included in this study.,,, The heart and ipsilateral lung were delineated as the OAR.
CT-based treatment planning was done using Eclipse TPS V8.6 with (Varian Medical System, Palo Alto, CA) Electron Monte Carlo algorithm.,,, Patients were treated using the Clinac 2100 linear accelerator. Depending on the curvature of the chest wall, the gantry angle and source surface distance were chosen such that the field entry was perpendicular to the skin surface. Depending on the PTV dimensions, suitable electron energy (9 MeV or 12 MeV) and an applicator with blocks were chosen. The dose was prescribed to the 90% isodose line enclosing the PTV, as per the recommendation of The American Association of Physicists in Medicine Task Group 25. Total dose to the PTV was 46 Gy in 23 fractions treated daily for 4.5 weeks.
To determine the bolus required, first the volume of the lung receiving >90% isodose line (VL90) was delineated using Boolean operator. The thickness of the chest wall above VL90 in every CT image was measured parallel to the beam axis, and the tissue deficit was calculated to compensate for it. The depth of the 90% isodose line inside the tissue was measured and used to delineate a contour parallel to the chest wall using a software tool in Eclipse. The overlap of this contour with the lung, derived the volume to be compensated (VC90).
The bolus material used was dental wax. Dental wax has a density of 1.02 g/cc and is available as thin rectangular sheets of dimension 16.5 cm × 9.2 cm with a thickness of 1.5 mm. The average HU for wax material in CT is −120, which is nearly equal to that of the chest wall tissue (average HU-100). A photon beam plan with multileaf collimator (MLC) was created with the isocenter at the skin and the appropriate gantry angle as in the electron beam plan. Each step of VC90 contours was fitted using multiple photon beams with MLC. A printout of the BEV was taken, with the MLC shape of all VC90. Dental wax used as bolus material did not require adhesive for fixing the layers. The printout was affixed on the wax which was cut manually according to the projected MLC shape. For every layer of bolus, the dimension was reduced in all sides in steps of 3 mm to achieve 30° inclinations. The edges of the bolus preceding the lower one were 3 mm shorter on all sides. At the same time, the isocenter and the crosshairs on the printout were transferred to the bolus.
As skin sparing is not recommended in postmastectomy CWRT, bolus was used on all treatment days. A commercially available uniform thickness 0.5 cm gel sheet bolus was first placed over the entire area of irradiation. This 0.5 cm bolus was considered while creating the VC90, minimizing the requirement of dental wax. Due to limitations of the available Eclipse software tools, initially 3 mm of bolus (2 sheets of dental wax) was included as the width of the VC90 to compensate 3 mm of tissue. Using Boolean operator, VC90 was reduced in steps of 3 mm posteriorly, and the bolus was included as the width of each reduced VC90. Bolus of 3 mm thickness was added in steps. This process was repeated until the VC90 was completely compensated. The resultant bolus obtained was referred to as a “STEP BOLUS” [Figure 1] because of its appearance. The bolus was finally linked to the electron field for dose calculation. When a sharp-edged bolus was kept partially in the line of the electron beam, it resulted in an edge effect. To reduce this sharp edge, the bolus was edited at the edges to make it tapered. This bolus was linked to the field and it was found that the hot and cold regions were reduced at the edges. By trial and error, the angle of inclination at the edges was found to be between 20° and 30° with respect to the chest wall surface perpendicular to the beam.,
A setup field was generated with photon fields in the plan created for Varian Clinac 2100, even though the treatment was planned for an electron beam. The setup field was only used to set the isocenter on the patient using Electronic Portal Imaging Device (EPID). A photon beam plan was generated with a prescription dose of only 2 cGy to avoid any accidental treatment using photon beam. In general, a setup field would be created with 0° gantry angle, but the cross-hair impression in the step bolus was created with a gantry angle θ. To make the cross-hairs of the setup field to coincide with the setup field on the step bolus, a shift in the cross-hair impression on the step bolus medially was calculated using the following formula:
x = t × tanθ
where, θ = Angle between 0° Gantry angle to treatment gantry angle
x = shift in cross-hair toward medial side in mm
t = thickness of the bolus at isocenter in mm
For example, if the thickness of step bolus used at the patient's isocenter (t) was 9 mm and the angle θ was 20°. Then, the shift (x) was calculated using above formula,
x = 9 mm × tan20°
= 3.28 mm
The shift of 3.28 mm at the isocenter was done on the step bolus toward the medial side and made to coincide with the setup field center. The new isocenter was marked on the bolus. The custom-made step bolus was localized and fixed to the thermoplastic mould matching the final shifted new isocenter drawn on the bolus to that of the planned isocenter on the thermoplastic mould. This step bolus along with the regular bolus of 0.5 cm was used on all the treatment days.
The dose distribution was verified in an Alderson Rando Phantom with and without the step bolus [Figure 2]. On evaluation of the dose distribution, it was found that dose inhomogeneity within the PTV and the dose to the underlying heart and lungs was reduced on adding the step bolus. Verification CT and planning was done in eight patients with the step bolus in position. The verification CT scan was done with the same slice thickness as in the planning CT series. This verification CT was registered (matched) with the planned CT, and then, the treatment planning was done with the parameters already selected.
|Figure 2: Dose distribution with and without step bolus in Alderson Rando Phantom|
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| > Results|| |
The modulated dose distribution showed that the dose to the lung and heart was minimized with step bolus [Figure 3]. The dose volume histogram for lung and heart without and with step bolus is shown in [Figure 4]. The dose received by 10%, 20%, 30%, 50%, and 70% (D10, D20, D30, D50, and D70) of the lung volumes along with mean lung dose in percentage are summarized in [Table 1] and dose received by 10% of the heart volume (D10) with mean heart dose % are summarized in [Table 2]. The addition of step bolus definitely improved dose distribution to the PTV with reduced dose to the lung and heart. The PTV plan objective of V95 >95% was achieved in all patients.
|Figure 4: Dose-volume histogram showing the dose received by the lung (Yellow line) and heart (Pink line) without (□) and with bolus (Δ)|
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|Table 1: Dose received by lung and mean lung dose without and with step bolus in percentage|
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|Table 2: Dose received by heart and mean heart dose without and with step bolus in percentage|
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Patients were assessed weekly during radiotherapy and followed up from 1 month after the end of radiation to a maximum period of 5 years (median follow up 32 months). Skin reaction was graded using RTOG grading system. A total of 47 patients developed Grade 2 skin reaction by the end of radiotherapy. Only one patient progressed to Grade 3 skin reaction. All reactions were treated conservatively and healed in 2–3 weeks after completion of treatment. At follow-up, all patients had only Grade 1 late tissue morbidity in the skin and subcutaneous tissue.
Among the 48 patients treated, only one patient developed acute pneumonitis. This patient had undergone surgery at another hospital and did not have complete axillary dissection. She required radiation to the chest wall, SCL, axillary, and IMN regions. The chest wall and IMN regions were treated with electrons with a step bolus, and the SCL and axillary regions were treated with conformal 6 MV photons using anteroposterior fields. The patient had completed radiation in September 2011 and reported in November 2011 with complaints of dry cough. Chest X-ray and CT chest revealed radiation pneumonitis. The patient was treated conservatively with steroids and antibiotics. Symptoms improved. A repeat CT chest done in 2015 showed only a fibrous band in the upper zone. The patient at 4 years after treatment is on regular follow-up and is clinically asymptomatic and disease free. There was no radiation-related cardiac event. A 75-year-old patient with previously diagnosed ischemic heart disease received radiotherapy to the chest wall on the right side, followed by tamoxifen. She did not receive chemotherapy due to her age and comorbid condition. She died due to myocardial infarction 9 months after radiotherapy.
The median follow-up was 32 months. At 5 years, 29 patients were alive. Twenty-two patients developed systemic metastases and 24 patients were disease free. One patient did not come for follow-up after 6 months of completion of treatment. No local recurrences were observed in the patients who were followed up. One patient died of myocardial infarction which was unrelated to the radiation treatment given. A total of 17 patients died due to metastasis and progressive disease.
| > Discussion|| |
Many methods of delivering conformal PMRT resulting in good local control and reduced complications to normal tissues are available today. In those patients in whom conformal photon plans are not optimal, conformal electron irradiation with bolus is an option. Earlier techniques for electron beam therapy used individual wax strips over a wax base plate as described by Archambeau et al. These lacked dose specification and did not address the nonuniformity of the postoperative chest wall. Perkins et al. developed a customized electron bolus using a 3D planning system using modeling wax with computer controlled milling device and algorithm as described by Antolak et al. Some reports in literature on electron beam techniques for PMRT consider the chest wall as a structure of equal thickness and a bolus of 0.5 cm uniform thickness is used for improving the skin dose. They have used multiple fields of different electron energies to include the internal mammary region. This would have resulted in dose inhomogeneity at field junctions. Using dental wax as a custom-made bolus for electron beam radiotherapy has been reported to be a well-tolerated treatment both regarding acute and late morbidity. In addition to uniform dose distribution, there was a significant reduction in doses to OAR.,
The current study is a report from a single institution on the use of CT-based 3D planning to create a custom-made step bolus using dental wax for PMRT chest wall radiation with electron beam therapy. The main advantage of this technique is that the chest wall including internal mammary nodal regions could be treated with a single field using single energy electrons. This avoided dose inhomogeneity at field junctions. This technique can be done in any institution with access to CT and 3D planning even in the absence of a milling device to make a custom-made bolus. The main disadvantage of this technique is that the making of the bolus is a time-consuming process.
Skin reactions were observed to be more with electron than with photon beam treatment. In addition, the step bolus helped to deliver dose to the skin. However, the skin toxicity was within acceptable limits. Only one patient developed acute pneumonitis indicating that the lung dose was acceptable in most patients when the step bolus was used. She had classical findings of radiation pneumonitis. This patient had required radiation to the chest wall, SCL, axillary, and IMN regions. In the literature, radiation pneumonitis after PMRT has been reported in 1% of patients without nodal and 4% with nodal irradiation. There was one patient who developed a cardiac event; however, she had received radiotherapy to the right chest wall. The myocardial infarction was attributed to her elderly age and comorbid conditions. Brachial plexus toxicity has been reported following radiation to SCL region and is more commonly associated when axillary nodal regions are included with SCL radiation. However, dose to brachial plexus in our study was within the recommended dose limit and no toxicity was observed.
| > Conclusion|| |
For postmastectomy CWRT, we first consider conformal photon tangential fields. If dose distribution to the target volume or the doses to the underlying heart and lung are not acceptable, conformal electron beam therapy is used. This study describes a method of conformal electron therapy for the postmastectomy chest wall and internal mammary region. It is suitable for institutions which do not have facilities of a milling machine and electron arc therapy. Preparation of a custom-made bolus called “step bolus” with easily available dental wax for electron beam therapy with the help of CT scan and TPS is described. This step bolus adequately compensated for the dose variation due to the individual patient's anatomy and variation in the chest wall thickness secondary to the surgical procedure. The main advantage of this technique is that the chest wall including the internal mammary nodal regions could be treated with single field and single energy electrons, this avoided dose inhomogeneity at field junctions. In addition, it provided good dose distribution to the target and low doses to the heart and lung.
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Conflicts of interest
There are no conflicts of interest.
| > References|| |
Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Early breast cancer trialists' collaborative group. Lancet 2000;355:1757-70.
Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al.
Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish breast cancer cooperative group DBCG 82c randomised trial. Lancet 1999;353:1641-8.
Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, et al.
Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956-62.
Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al.
Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005;366:2087-106.
EBCTCG (Early Breast Cancer Trialists' Collaborative Group), McGale P, Taylor C, Correa C, Cutter D, Duane F, et al.
Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014;383:2127-35.
Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, et al.
Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 2015;373:317-27.
Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, et al.
Regional nodal irradiation in early-stage breast cancer. N Engl J Med 2015;373:307-16.
Thorsen LB, Offersen BV, Danø H, Berg M, Jensen I, Pedersen AN, et al.
DBCG-IMN: A Population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol 2016;34:314-20.
Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, et al.
Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med 1997;337:949-55.
Opp D, Forster K, Li W, Zhang G, Harris EE. Evaluation of bolus electron conformal therapy compared with conventional techniques for the treatment of left chest wall postmastectomy in patients with breast cancer. Med Dosim 2013;38:448-53.
Khan FM, Doppke KP, Hogstrom KR, Kutcher GJ, Nath R, Prasad SC, et al
. Clinical electron-beam dosimetry: Report of AAPM Radiation Therapy Committee Rask Group No. 25. Med Phys 1991;18:73-109.
Gerbi BJ, Antolak JA, Deibel CF, Followill DS, Herman MG, Higgins PD. TG70: Recommendations for clinical electron beam dosimetry: Supplement to the recommendation of Task Group 25. Med Phys 2009;36:3239-79.
Khan FM. Basic physics of electron beam therapy. In: Frontiers of Radiation Therapy and Oncology. Vol. 25. Basel: Karger; 1991. p. 10-29.
Salguero FJ, Palma B, Arrans R, Rosello J, Leal A. Modulated electron radiotherapy treatment planning using a photon multileaf collimator for post-mastectomized chest walls. Radiother Oncol 2009;93:625-32.
Zackrisson B, Karlsson M. Matching of electron beams for conformal therapy of target volumes at moderate depths. Radiother Oncol 1996;39:261-70.
Li XA, Tai A, Arthur DW, Buchholz TA, Macdonald S, Marks LB, et al.
Variability of target and normal structure delineation for breast cancer radiotherapy: An RTOG multi-institutional and multiobserver study. Int J Radiat Oncol Biol Phys 2009;73:944-51.
Antolak JA, Starkschall G, Bawiec ER, Ewton JR, Hogstrom KR. Implementation of an automated electron bolus fabrication system for conformal electron radiotherapy. Proceedings of the 11th
International Conference on the Use of Computers in Radiation Therapy. Handley Printers Limited, Cheshire; 1994. p. 162-3.
Fraass B, Doppke K, Hunt M, Kutcher G, Starkschall G, Stern R, et al.
American association of physicists in medicine radiation therapy committee task group 53: Quality assurance for clinical radiotherapy treatment planning. Med Phys 1998;25:1773-829.
Podgorsak EB. Radiation Oncology Physics: A Handbook for Teachers and Students. Vienna: International Atomic Energy Agency; 2005.
Ding GX, Cygler JE, Yu CW, Kalach NI, Daskalov G. A comparison of electron beam dose calculation accuracy between treatment planning systems using either a pencil beam or a Monte Carlo algorithm. Int J Radiat Oncol Biol Phys 2005;63:622-33.
Kirova YM, Campana F, Fournier-Bidoz N, Stilhart A, Dendale R, Bollet MA, et al.
Postmastectomy electron beam chest wall irradiation in women with breast cancer: A clinical step toward conformal electron therapy. Int J Radiat Oncol Biol Phys 2007;69:1139-44.
Kudchadker RJ, Hogstrom KR, Garden AS, McNeese MD, Boyd RA, Antolak JA, et al.
Electron conformal radiotherapy using bolus and intensity modulation. Int J Radiat Oncol Biol Phys 2002;53:1023-37.
Low DA, Starkschall G, Bujnowski SW, Wang LL, Hogstrom KR. Electron bolus design for radiotherapy treatment planning: Bolus design algorithms. Med Phys 1992;19:115-24.
Andic F, Ors Y, Davutoglu R, Baz Cifci S, Ispir EB, Erturk ME, et al.
Evaluation of skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy. J Exp Clin Cancer Res 2009;28:41.
Archambeau JO, Forell B, Doria R, Findley DO, Jurisch R, Jackson R, et al.
Use of variable thickness bolus to control electron beam penetration in chest wall irradiation. Int J Radiat Oncol Biol Phys 1981;7:835-42.
Perkins GH, McNeese MD, Antolak JA, Buchholz TA, Strom EA, Hogstrom KR, et al.
A custom three-dimensional electron bolus technique for optimization of postmastectomy irradiation. Int J Radiat Oncol Biol Phys 2001;51:1142-51.
Spierer MM, Hong LX, Wagman RT, Katz MS, Spierer RL, McCormick B, et al.
Postmastectomy CT-based electron beam radiotherapy: Dosimetry, efficacy, and toxicity in 118 patients. Int J Radiat Oncol Biol Phys 2004;60:1182-9.
Wennberg B, Gagliardi G, Sundbom L, Svane G, Lind P. Early response of lung in breast cancer irradiation: Radiologic density changes measured by CT and symptomatic radiation pneumonitis. Int J Radiat Oncol Biol Phys 2002;52:1196-206.
Taghian AG, Assaad SI, Niemierko A, Kuter I, Younger J, Schoenthaler R, et al.
Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 2001;93:1806-11.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]