|Year : 2013 | Volume
| Issue : 3 | Page : 452-455
Carotid sparing hypofractionated tomotherapy in early glottic cancers: Refining image guided IMRT to improve morbidity
Sanjoy Chatterjee1, Sourav Guha1, Sriram Prasath2, Indranil Mallick1, Rimpa Achari1
1 Department of Radiotherapy, Tata Medical Center, Kolkata, India
2 Department of Medical Physics, Tata Medical Center, Kolkata, India
|Date of Web Publication||8-Oct-2013|
Tata Medical Center, 14 MAR (EW), Newtown, Kolkata-700 156
Source of Support: None, Conflict of Interest: None
Objective: Carotid artery damage has been reported secondary to radiotherapy. We report the feasibility of implementing hypofractionated laryngeal irradiation using carotid sparing tomotherapy (HT) and analyze the image guidance (IG) policy.
Materials and Methods: Five patients with early glottic cancer (EGC) had radiotherapy using 3D conformal technique (conf) while repeat treatment plans were produced with helical tomotherapy using carotid sparing techniques (cstomo). Inverse and forward planned dose volume histograms were analyzed. Three hundred and sixty four daily images of 14 patients having daily Megavoltage head and neck CT imaging prior to irradiation were analyzed to assess errors.
Results: There was no significant difference in the maximum and mean dose to the PTV (P = 0.058, 0.66). The left / right carotid median doses were significantly less in the cstomo plans as compared to conf plans (P = 0.0001/ 0.026). Cstomo plans had significantly better PTV Conformity Index (CI) (P = 0.0006) with comparable Homogeneity Index. A CTV-PTV margin of 5.3, 4, 5.3 cm in the 3 axes were calculated using Van Herks formula. After average shifts from imaging for first 5 fractions (AS5) were applied to remaining fractions, the residual shifts in the calculated CTV-PTV margins reduced to 2.9, and 2.1 in the X, Y axes respectively allowing further adaptation of PTV margin from fraction 6.
Conclusions: Carotid sparing was possible using cstomo plans with significantly better conformity. Applying AS5 could enable us to reduce the PTV (3 mm) margin in X, Y axes for the remaining 15 fractions.
Keywords: Carotid sparing tomotherapy, conformity index, homogeneity index
|How to cite this article:|
Chatterjee S, Guha S, Prasath S, Mallick I, Achari R. Carotid sparing hypofractionated tomotherapy in early glottic cancers: Refining image guided IMRT to improve morbidity. J Can Res Ther 2013;9:452-5
|How to cite this URL:|
Chatterjee S, Guha S, Prasath S, Mallick I, Achari R. Carotid sparing hypofractionated tomotherapy in early glottic cancers: Refining image guided IMRT to improve morbidity. J Can Res Ther [serial online] 2013 [cited 2019 Dec 15];9:452-5. Available from: http://www.cancerjournal.net/text.asp?2013/9/3/452/119349
| > Introduction|| |
Squamous cell carcinoma larynx is one of the commonest head and neck malignancy  with approximately 30-40% tumors presenting in early stage.  There is a large burden of laryngeal cancers in India , and amongst all stages early stage glottic carcinoma (EGC) (T1-T2 N0) has favorable prognosis with a 5 year locoregional control rates of over 90%. , Organ preservation radiotherapy has often been used in the treatment of EGC with surgery reserved for salvage. Conventionally, radiation therapy has been delivered using two parallel opposed radiation fields, often using hypofractionated schedules  thereby irradiating the carotid arteries to a high dose [Figure 1]. Carotid artery damage post radiotherapy leads to increased thickness of carotid intima-media subsequently resulting in increased incidence of atherosclerosis and higher chance of cerebrovascular accidents. ,,, IMRT, has the benefits of improved conformity to the planning target volume (PTV) and the sparing of organs at risk (OAR).  Few investigators have explored the idea of reducing carotid artery dose in the treatment of EGC, using conventional dose fractionation. ,,
|Figure 1: 3DCRT plan with lateral parallel opposed beams. The carotids which lies just adjacent to the planning target volume also being irradiated to the same dose as the planning target volume.|
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The practicality of implementing a hypofractionated image guided intensity modulated radiotherapy schedule and thereby a robust image guidance in steep dose gradient has not been reported. We hereby report the feasibility of implementation of such hypofractionated carotid sparing radiotherapy technique using helical tomotherapy (HT).
| > Material and Methods|| |
Patients with T1N0M0 squamous cell carcinoma of the vocal cord suitable for treatment using a hypofractionated radiotherapy schedule were selected for the study. All patients were immobilized in supine position with a four point thermoplastic head and neck beam directional mask. Radiotherapy planning contrast enhanced (Iopamidol, 1mg/kg body weight) CT scans of 2.5 mm thickness were obtained. (Lightspeed extra GE CT scanner, 16 slice) from the vertex till 5 cm below the sternoclavicular joint as per in-house hospital protocol. CT scan images were imported to the Eclipse (Eclipse- Version 10; Varian Medical Systems Inc. Palo Alto, USA) treatment planning system for contouring purposes.
The target volumes were delineated following our institutional guidelines for contouring. The clinical target volume (CTV) extended superiorly from the cranial border of the thyroid cartilage, inferiorly till the caudal end of the cricoid cartilage, anteriorly including the anterior edge to the thyroid cartilage, posteriorly included the arytenoid cartilage and laterally the entire thyroid cartilage was included within the CTV. A 5 mm margin was applied to CTV in all axes as per institutional policy to create the planning target volume (PTV). If the carotid artery was included within the PTV after CTV-PTV margin expansion, the PTV was edited off the carotid arteries.
The contoured organs at risk included bilateral carotid arteries extending superiorly till skull base and inferiorly till sternoclavicular joint, spinal cord, thyroid gland, constrictor muscles and the submandibular gland. For each patient, two treatment plans were generated. The first plan was generated using forward planned 3D conformal technique (conf) and a second plan with inverse planned technique using helical tomotherapy (HT) using carotid sparing techniques (cstomo).
A dose of 55Gy in 20 fractions was prescribed to the beam isocenter for the conf plan and for cstomo plan at least 95% of the PTV was required to be covered by the 95% isodose of 55Gy. The conventional forward planned technique was optimized using multiple field in fields and was deemed acceptable only if the plan fulfilled the ICRU recommendations, although they were optimized even further, and was used for treatment purposes. HT was used to produce carotid sparing intensity-modulated radiotherapy (IMRT) with carotid sparing [Figure 2]. Details of HT planning process are beyond the scope of this article but more details on the procedure are available in another article published by our group.  In summary, HT uses field with, pitch and modulation factor variations to optimize plans. A field width of 1 cm, modulation factor of 2.0 and pitch of 0.3 was used to produce the cstomo plans. A posterior planning structure (dummy) was contoured and dose constraints applied to ensure minimal dose dumping outside the planning target volume (PTV).
As discussed above, cstomo plans were accepted when at least 95% (relative volume) of the PTV received 95% of the prescription dose with optimal sparing of the spinal cord and carotid arteries.
|Figure 2: Carotid sparing tomotherapy technique. The carotids were being spared significantly without compromising on the PTV coverage.|
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A 0.5 cm thick tissue-equivalent bolus was fixed to the beam directional mask anterior to the anterior commisure of the thyroid cartilage if the anterior commisure was thought to be involved with invasive carcinoma. Daily verification of the exact positioning of the bolus and of the patient was assured before treatment by experienced radiographers. Inverse and forward planned dose volume histograms were analyzed and the carotid maximum, mean, median doses were compared. Similarly, the PTV maximum and median doses were compared between the two plans for each patient. The homogeneity index (HI) for all plans was calculated and compared using the formula (D2-D98 / Dp) x100% where D2, D98 and Dp represent the doses to 2%, 98% and prescribed dose to the PTV, respectively.  We calculated the conformity index (CI) for all using the formulaTvRI X TvRI / Tv X VRI where TvRI: Target volume covered by the reference isodose, VRI Volume of the reference isodose, Tv: Target volume. 
Analysis of Image guidance policy were undertaken to analyze if further adaptation of CTV-PTV margin was possible during treatment such that further plans could evaluate increased sparing of carotid arteries. Three hundred sixty four daily images of 14 patients who had Megavoltage CT imaging prior to head and neck irradiation using HT were analyzed retrospectively to assess systematic errors using Van Herks formula.  To develop a practical adaptive image guidance policy, we also explored the systematic errors from the first 5 fractions (AS5) of treatment separately and then applied the shifts in the remaining 15 fractions. The residual shifts that were required for the patients after applying AS5 were calculated to assess if the PTV margin could be reduced further after 5 fractions.
HT couch produces 'sag' which was also evaluated for our unit and was found to be negligible without any load. The sag was reproducible for a given weight hence any calculation of variations in the positioning was not affected by the sag.
Given the small sample size log rank test was used to compare the PTV and OAR doses between the conf and cstomo plans.
| > Results|| |
(a) PTV coverage: The coverage of PTV (95% prescribed dose) was compared between the two plans and there was no significant difference [Table 1].
|Table 1: Comparison of coverage of PTV (95% prescribed dose) between the two plans|
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The dose to the PTV was compared using conformity index (CI) and homogeneity index (HI). The HI of cstomo versus conf plans were 14.05 and 14.86 (P = 0.86) and CI of cstomo versus conf plans were 0.75 vs. 0.43 (P = 0.0006).
(b) Carotid dose comparison: On cstomo plans the left carotid artery mean and median doses were 15.36 Gy and 3.42 Gy and right carotid artery mean and median doses were 16.52 Gy and 4.48 Gy as compared to mean and median doses of and 25.47 Gy and 29.02 Gy to left carotid and 26.61 and 29.02 Gy to right carotid respectively on conf plans. The difference in the right and left mean and median doses were statistically significant (P = 0.043/0.043 and 0.043/0.043) [Table 2].
|Table 2: Comparison of Mean and Median doses to carotids by cstomo and conf technique|
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There was statistically significant reduction in volume of the carotid arteries irradiated using cstomo when compared to conf plans. The mean volume of both the carotids receiving 5 Gy, 15 Gy, 25 Gy and 50 Gy were also evaluated and compared [Table 3].
|Table 3: Comparison between the volume of carotids receiving 5Gy, 15Gy, 25Gy and 50Gy by the two techniques|
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(c) Dose to Spinal cord and Esophagus: The maximum dose to the spinal cord was compared between the two plans [Table 4].
|Table 4: Comparison of the maximum dose to the spinal cord between the two plans|
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The oesophagus started inferior to the cricoids and was not within the PTV. The posterior dummy mentioned above included the oesophagus and the maximum point dose recorded was less than 45 Gy in all the five patients.
(d) Image guidance : A PTV margin of 5.3, 4 and 5.3 mm was calculated using Ven Herks formula based on the daily image matching shifts, corresponding to a 2.3 mm, 1.1 mm and 5.5 mm mean shift recorded in the in the X, Y and Z axes.
As discussed, average shifts from imaging for first 5 fractions (AS5) were calculated for each of the patients and then this shift was reapplied to the remaining fractions to ascertain if this could necessarily reduce the residual corrective shifts for the patients in the remaining fractions. AS5 when applied to further fractions reduced the required CTV-PTV margins to 2.9, 2.1 and 5.5 mm in the X, Y and Z axes, respectively.
| > Discussion|| |
In early glottic malignancies treated using radiotherapy the carotid arteries located on either side of the target volume are positioned within the path of the lateral parallel opposed beams and receive almost the full prescribed dose. Dorresteijn et al.,  calculated that the 15-year cumulative risk of stroke after radiotherapy to the neck was 12.0%. Cheng et al.,  in his study showed patients with nasopharyngeal and laryngeal carcinoma had more chances of cerebrovascular symptoms, and more frequent carotid artery stenosis post radiotherapy and the risk factors included age, smoking, coronary heart disease, previous stroke, no head and neck surgery, time interval from radiotherapy, and the site of primary tumor. In order to reduce the dose to bilateral carotids few investigators have explored carotid sparing techniques while treating early stage glottic malignancies using radical external beam radiotherapy. These articles have however not reported on the dose volume correlation of the carotids and have not used hypofractionated schedule as is commonly used worldwide.
Practicality of image guidance or adaptive strategies in steep dose gradients has also not been discussed in any of the studies. In our study, as was expected, the mean and the median dose to the bilateral carotids were significantly lower using helical tomotherapy when compared to the conventional techniques, without compromising on the HI or CI. Importantly though, we report the volume of carotid artery receiving 5 Gy, 15 Gy, 25 Gy and 50 Gy, which enables readers to have more clear idea on optimizing the carotid artery dose using inversed planned techniques. The cstomo plans showed significantly reduced volume of both the carotids irradiated to any dose, implying that the higher dose reduction to the carotid artery was achieved not at the expense of having increased volumes of lower doses to the carotid arteries.
The dose to the spinal cord was higher using HT as the system although well within the tolerance of the spinal cord. This can be explained as the HT system used increased contribution of the dose from the anterior and posterior sides to reduce dose from the lateral sides such that entry and exit dose to the carotids could be lowered. Looking at the CTV-PTV margins it is apparent that the patients would require daily image guidance, especially for a steep dose gradient like cstomo. But using AS5 one could explore further lowering of the CTV-PTV margins thereby allowing adaptive plans from the 6 th fraction. Reduction in CTV-PTV margin in X and Y axes for 15 fractions could allow further reduction in carotid dose or even the constrictor muscles.
| > Conclusion|| |
Helical tomotherapy allows significantly lower dose to the bilateral carotids while the planning target volume is more conformal and equally homogenous and conformal, possibly preventing carotid artery damage. Daily imaging allows more security especially when working in high dose gradients and it is safer to do daily image guidance. This concept is now being evaluated prospectively by us within a clinical study (CARSREL) whereby carotid artery ultrasound is being done pre and post treatment on patients treated with carotid sparing helical tomotherapy for EGC, to ascertain if the dosimetric benefits mentioned above could translate into clinical improvements.
| > References|| |
|1.||Sanghvi LD, Rao DN, Joshi S. National Cancer Registry Project. Semin Surg Oncol 1989;5:305-9. |
|2.||Surveillane Epidemiology and End Results. Available from: http://seer.cancer.gov/statfacts/html/laryn.html [Last accessed on 2013 Feb 15]. |
|3.||Kapil U, Singh P, Bahadur S, Dwivedi SN, Singh R, Shukla N. Assessment of risk factors in laryngeal cancer in India: A case- control study. Asian Pac J Cancer Prev 2005;6:202-7. |
|4.||Indian Council of Medical Research. Available from: http://icmr.nic.in/cancer.pdf [Last accessed on 2013 Feb 15]. |
|5.||Chera BS, Amdur RJ, Morris CG, Kirwan JM, Mendenhall WM. T1N0 to T2N0 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy. Int J Radiat Oncol Biol Phys 2010;78:461-6. |
|6.||Teshima T, Chatani M, Inoue T. Radiation therapy for early glottic cancer (T1N0M0): Prospective randomized study concerning radiation field. Int J Radiat Oncol Biol Phys 1990;18:119-23. |
|7.||The Royal College of Radiologists. Available from: http://www.rcr.ac.uk/docs/oncology/pdf/Dose-Fractionation_Final.pdf [Last accessed on 2013 Feb 15]. |
|8.||Brown PD, Foote RL, McLaughlin MP. A historical prospective cohort study of carotid artery stenosis after radiotherapy for head and neck malignancies. Int J Radiat Oncol Biol Phys 2005;63:1361-7. |
|9.||Dorresteijn LD, Kappelle AC, Boogerd W. Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 2002,20:282-288. |
|10.||So NM, Lam WW, Chook P. Carotid intima-media thickness in patients with head and neck irradiation for the treatment of nasopharyngeal carcinoma. Clin Radiol 2002;57:600-3. |
|11.||Shariat M, Alias NA, Biswal BM. Radiation effects on the intima-media thickness of the common carotid artery in post-radiotherapy patients with head and neck malignancy. Postgrad Med J 2008;84:609-12. |
|12.||Chatterjee S, Willis N, Locks SM, Mott JH, Kelly CG. Dosimetric and radiobiological comparison of helical tomotherapy, forward-planned intensity-modulated radiotherapy and two-phase conformal plans for radical radiotherapy treatment of head and neck squamous cell carcinomas. Br J Radiol 2011;84:1083-90. |
|13.||Gomez D, Cahlon O, Mechalakos J, Lee N. An investigation of intensity-modulated radiation therapy versus conventional two-dimensional and 3D-conformal radiation therapy for early stage larynx cancer. Radiat Oncol 2010;5:74-82. |
|14.||Rosenthal DI, Fuller CD, Barker JL Jr, Mason B, Garcia JA, Lewin JS, et al. Simple carotid sparing Intensity modulated technique and preliminary experience for T1-T2 glottic cance. Int J Radiat Oncol Biol Phys 2010;77:455-61. |
|15.||Chera BS, Amdur RJ, Morris CG, Mendenhall WM. Carotid sparing Intensity Modulated radiotherapy for early stage squamous cell carcinoma of true vocal cord. Int J Radiat Oncol Biol Phys 2010;77:1380-5. |
|16.||Chatterjee S, Mott JH, Smyth G, Dickson S, Dobrowsky W, Kelly CG. Clinical challenges in the implementation of a tomotherapy service for head and neck cancer patients in a regional UK radiotherapy centre. Br J Radiol 2011;84:358-66. |
|17.||Mohan R, Morris M, Lauve A, Schmidt-Ullrich R. Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: Dosimetric results. Int J Radiat Oncol Biol Phys 2003;56:573-85. |
|18.||Van′t Riet A, Mak AC, Moerland MA. A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: Application to the prostate. Int J Radiat Oncol Biol Phys 1997;37:731-6. |
|19.||van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol 2004;14:52-64. |
|20.||Dorresteijn LD, Kappelle AC, Boogerd W. Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 2002;20:282-8. |
|21.||Cheng SW, Wu LL, Ting AC. Irradiation-induced extracranial carotid stenosis in patients with head and neck malignancies. Am J Surg 1999;178:323-8. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]