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Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors

Implications of contrast-enhanced CT-based and MRI-based target volume delineations in... Journal of Cancer Research and Therapeutics January-March 2008 | Volume 4 | Issue 1 CONTENTS Editorial Criteria for deciding cost-effectiveness for expensive new anti-cancer agents Rajiv Sarin .............................................................................................................................................................1 Original Articles The effect of three mouthwashes on radiation-induced oral mucositis in patients with head and neck malignancies: A randomized control trial PD Kumar Madan, PS Sequeira, Kamalaksha Shenoy, Jayaram Shetty .............................................................3 Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors Niloy R Datta, Rajasekar David, Rakesh K Gupta, Punita Lal ..............................................................................9 Radiofrequency ablation of hepatic metastasis: Results of treatment in forty patients GK Rath, PK Julka, S Thulkar, DN Sharma, Amit Bahl, S Bhatnagar .................................................................14 Execution of mantle fi eld with multileaf collimator: A simple approach Ramachandran Prabhakar, Kunhi Parambath P Haresh, Pappiah S Sridhar, Macharla A Laviraj, Pramod K Julka, Goura K Rath ...........................................................................................................................18 Prognostic and diagnostic value of serum pseudocholinesterase, serum aspartate transaminase, and serum alinine transaminase in malignancies treated by radiotherapy Arun Chougule, Sofi a Hussain, Dwaraka Prasad Agarwal .................................................................................21 Review Article An overview on applications of optical spectroscopy in cervical cancers C Murali Krishna, GD Sockalingum, MS Vidyasagar, M Manfait, Donald J Fernanades, BM Vadhiraja, K Maheedhar .......................................................................................................................................................26 Case Reports Radiotherapy for management of skin cancers in fi brodysplasia ossifi cans progressiva: A case report and review of the literature John Antony Frew, Charles G Kelly ....................................................................................................................37 Sarcomatoid squamous cell carcinoma of uterine cervix: Pathology, imaging, and treatment Milind Kumar, Amit Bahl, Daya Nand Sharma, Shipra Agarwal, Dhanapathi Halanaik, Rakesh Kumar, Goura Kishore Rath ............................................................................................................................................39 Brief Communications Chest wall metastasis from hepatocellular carcinoma in the absence of a primary: An unusual presentation Kaustav Talapatra, Reena Engineer, Jai Prakash Agarwal, Shilpa Vyas, Shyam Kishore Shrivastava .............42 Endobronchial metastasis of follicular thyroid carcinoma presenting as hemoptysis: A case report RAS Kushwaha, Sanjay Kumar Verma, Sanjay Vineet Mahajan ........................................................................44 Accelerated partial breast irradiation: An advanced form of hypofractionation Ashwini Budrukkar ..............................................................................................................................................46 Coexistence of carcinoma breast and Paget’s disease of bone S Sundaraiya, PK Pradhan, A Gupta, M Jain, SK Mishra, BK Das .....................................................................48 Letter to Editor Dysplastic hematopoiesis and underlying dysthyroidism Riad Akoum, Michel Saade, Wafi c Tabbara, Emile Brihi, Marwan Masri, Khaled Habib, Gerard Abadjian ........50 Reviewers’ List, 2007 ..............................................................................................................................51 The copies of the journal to members of the association are sent by ordinary post. The editorial board, association or publisher will not be responsible for non-receipt of copies. If any of the members wish to receive the copies by registered post or courier, kindly contact the journal’s / publisher’s offi ce. If a copy returns due to incomplete, incorrect or changed address of a member on two consecutive occasions, the names of such members will be deleted from the mailing list of the journal. Providing complete, correct and up-to-date address is the responsibility of the members. Copies are sent to subscribers and members directly from the publisher’s address; it is illegal to acquire copies from any other source. If a copy is received for personal use as a member of the association/society, one cannot resale or give-away the copy for commercial or library use. J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 53 Free full text available from Original Article www.cancerjournal.net Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors ABSTRACT Niloy R Datta, Rajasekar David , Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) 2 Rakesh K Gupta , constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative Punita Lal evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, Department of Radiation along with its implications for postoperative radiotherapy of brain tumors. Oncology, Rajiv Gandhi Cancer Institute and Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were Research Centre, New delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence Delhi, Department studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the of Radiotherapy and Radiodiagnosis and mean CTV (mean ± SD: −62.92 ± 93.99 cc; P = 0.006) and GTV (mean ± SD: −21.08 ± 36.04 cc; P = 0.014). These differences Imaging, Sanjay Gandhi were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for Postgraduate Institute low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be of Medical Sciences, Lucknow, India −106.7% and −62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of For correspondence: Dr. N.R. Datta, brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in Department of Radiation the regions of peritumoral edema. Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, KEY WORDS: Brain tumor, radiation therapy, target volumes, treatment planning Rohini, New Delhi - 110 085, India. E-mail: nrdatta@ yahoo.com INTRODUCTION edema, and adjacent normal brain parenchyma. These targets are better demarcated through T1 [1,3,4] Postoperative irradiation for brain tumors is an contrast and T2-weighted MRI images. accepted adjuvant treatment, especially for the [1] higher grades of brain tumors. Radiation portals The International Commission on Radiation Units [5] are now restricted to partial brain irradiation (ICRU)-report 50, had proposed that various target (PBI) rather than whole brain. This is based on the volumes be delineated during the radiation therapy evidences showing similar patterns of recurrence planning. These included, primarily, the gross target [2] for both the treatment strategies. However, volume (GTV), representing the gross tumor, and with the use of PBI, it becomes important that the clinical target volume (CTV) for the microscopic the treatment portals be designed and placed to presence of disease surrounding the GTV . The outlining effectively include both residual tumor volume and of these target volumes could be based on the various the adjoining regions of brain parenchyma, which imaging studies, namely contrast-enhanced CT or are likely to harbour microscopic disease. MRI. Planning target volume (PTV), defined with a margin of usually 0.5 to 1 cm surrounding the GTV Computed tomography (CT) and magnetic resonance or CTV, would depend on the treatment setup errors imaging (MRI) have been the two cornerstones in during the entire course of radiation therapy as [2] the imaging of brain tumors. CT images provide estimated by individual departments. The present valuable electron density information which is study therefore, aims to carry out a comparative mandatory for radiation therapy dose calculations, quantitative evaluation of the postoperative GTVs but CT has its limitations as far as soft tissue and CTVs for brain tumors, as visualized either on contrast is concerned. This could lead to difficulty contrast-enhanced CT or MRI, in patients referred for in accurate delineation of the tumor, peritumoral postoperative adjuvant radiotherapy. J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 9 Datta, et al.: Delineation of target volumes in brain tumors MATERIALS AND METHODS Statistical analyses were performed using SPSS statistical software for Windows, version 9.0 (SPSS Inc. Chicago, IL, A total of 21 patients, histopathologically proven as glioma USA). (all grades) and referred for postoperative radiotherapy were considered for this prospective study. All these patients were RESULTS immobilized using ORFIT thermoplastic cast (ORFIT industries, Belgium) and taken up for contrast-enhanced CT and MRI with Patients were usually referred for postoperative radiotherapy the cast in situ. within 2-3 weeks of the surgical procedure. Following simulation, contrast-enhanced CT and MRI were carried out at close intervals. The mean interval between surgery and CT: The study was conducted with the patients immobilized postoperative CT was 29 days (median: 21 days) while with on the flat couch of the diagnostic CT unit (Picker 5500, Picker MRI it was 26 days (median: 21 days). The mean interval International Inc, USA). Following contrast, axial cuts were between CT and MRI was 3 days (median: 1 day). Most of the usually taken from the vertex to the base of the skull, with a patients had glioblastoma multiforme and had undergone field of view (FOV) of 240 mm and a matrix size of 512 × 512. tumor decompression. The demographic details are listed in These were transferred to the radiation therapy treatment Table 1. planning (RTP) workstation (Isis-3D, Technologie Diffusion, France). All the target volumes delineated in MRI were significantly larger than in CT [Tables 1 and 2]. The mean CTV, consisting of MRI: MRI scans were taken with the standard head coil (1.5 T, peritumoral edema volume, delineated in MRI was 180.93 cc Magnetom, Siemens, Germany). A custom-made Perspex™ (SD: ± 117.70) as compared to 118.01 cc (SD: ± 82.94) in CT base plate, which could fit into the standard head coil but studies. Similarly, the mean GTV, comprising hyperintense was similar to the one used during CT acquisition, was used regions in contrast-enhanced T1W MRI images, was for fixing the cast during MRI. The images from the vertex 71.64 cc (SD: ± 58.42), while it was 50.56 cc (SD: ± 37.21) in to the base of the skull were obtained with spin-echo (SE) [6] contrast-enhanced CT studies [Figure 1]. Compared to MRI, sequence, which has the least image distortions. The CT significantly underestimated the volumes, resulting conventional SE T2-weighted (TR/TE1, 2/n: 3000/12, 80/1), in a mean difference between the imaging modalities plain, and post-gadolinium contrast T1-weighted (1012/14/2) (CT volume − MRI volume) of −62.92 ± 93.99 cc (P = 0.006) axial MR images were obtained using a 256 × 256 matrix for CTV and −21.08 ± 36.04 cc (P = 0.014) for GTV [Table 2]. size, a bandwidth of 65 Hz/pixel, and an FOV of 250 mm. The percentage difference calculated taking the CT volume The MR images were transferred to the RTP workstation for as baseline [(CT-based volume − MRI-based volume)/ treatment planning. CT-based volume × 100] shows that for CTV and GTV, the mean percentage differences was −106.7% (SD: ± 177.3) and −62.6% Postoperative target volumes for residual GTV and CTV were (SD: ± 131.8), respectively [Figure 2]. drawn on contrast-enhanced CT and MRI images as per the [5] recommendations in ICRU report 50. Since all these patients had undergone prior surgery, ranging from just biopsy to Table 1: Patient demography (n = 21) subtotal resection, the residual GTV and the peritumoral Characteristics Distribution edema were estimated separately for each imaging modality. Age (in years) 42.2 ± 15.5* The details of the delineation of various postoperative target (range: 14-79) volumes, done by an experienced neuroradiologist along with Location of tumor Frontal:parietal:temporal:occipital 8:3:8:2 radiation oncologist on the postoperative contrast-enhanced Operative procedure CT and MRI, are as follows: Biopsy:DPN:STR 1:15:5 Histology Astrocytoma:oligoastrocytoma 19:2 For phase I treatment, CTV was marked on contrast-enhanced Tumor grade CT as regions of brain parenchyma showing hypodensity Grade I:II:III:IV 3:2:3:13 surrounding the residual tumor with any area of adjoining Tumor dose (Gy) 61.1 ± 4.7 mass effect. On MRI, the hyperintense region on T2W images (range: 50-66) Gross tumor volume (cc) was delineated as CTV. For the phase II treatment, the contrast- CT 50.57 ± 37.21 enhanced regions depicting a mass effect was considered (range: 4.22-146.72) as residual tumor (GTV) for both contrast-enhanced CT and MRI 71.64 ± 58.42 [7] T1W contrast studies. The actual volumes (in cc) for the (range: 9.78-253.97) Peritumoral edema volume (cc) corresponding CTVs and GTVs were noted from the RTP CT 118.01 ± 82.94 workstation in contrast-enhanced CT-based and MRI based (range: 12.43-295.55) plans. A total dose of 60 Gy was delivered in two phases: 45 Gy MRI 180.93 ± 117.70 to the CTV in phase I and 15 Gy, with reduced field sizes, to (range: 23.62-494.21) the GTV alone in phase II. *Mean ± standard deviation; DPN: Decompression; STR: Subtotal resection 10 J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 Datta, et al.: Delineation of target volumes in brain tumors Table 2: Mean difference in clinical target volumes and postoperative gross target volumes as evident on contrast-enhanced computed tomography and magnetic resonance imaging for (a) all patients, (b) grades I and II, and (c) grades III and IV Volume CECT-based (cc) (CECT) MRI-based (cc) (MRI) Difference (cc) CECT−MRI P-value* A: All patients (n = 21) CTV 118.01 ± 82.94 180.93 ± 117.70 −62.92 ± 93.99 0.006 GTV 50.57 ± 37.21 71.64 ± 58.42 −21.08 ± 36.04 0.014 B: Grades I and II (n = 5) CTV 116.37 ± 78.14 239.51 ± 178.09 −123.14 ± 117.93 0.080 GTV 50.07 ± 54.65 101.36 ± 98.10 −51.29 ± 57.63 0.117 C: Grades III and IV (n = 16) CTV 118.52 ± 86.84 162.62 ± 92.26 −44.10 ± 80.51 0.045 GTV 50.72 ± 32.39 62.35 ± 39.96 −11.63 ± 21.13 0.044 *Paired sample ‘t’ test; CTV: Clinical target volume; GTV: Postoperative residual gross target volume. All volumes indicate mean ± standard deviation 500 7 (a) (a) 1 0 50 100 150 200 250 300 350 400 450 500 0 -600 -500 -400 -300 -200 -100 0 CTV on CECT (cc) % difference (CTV) (b) 200 8 150 6 (b) 0 50 100 150 200 250 300 -550 -500 -450 -400 -350 -300 -250 -200 -150 -100 -50 0 50 GTV on CECT (cc) % difference (GTV) Figure 1: Scatter plot for the various ICRU report 50 volumes - clinical Figure 2: Histogram showing distribution of patients and percentage target volumes (CTV) and gross target volumes (GTV) - as estimated differences between contrast-enhanced CT and MRI for clinical target by contrast-enhanced CT and MRI studies. The curves Þ tted represent volumes (CTV) and gross target volumes (GTV). The normal distribution 2 2 linear Þ t. (a) CTV: r = 0.77, (b) GTV: r = 0.86. curve for the frequency distribution is also shown. (a) CTV (mean ± SD: −106.7% ± 177.3) and (b) GTV (mean ± SD: −62.6% ± 131.8). The differences in the various target volumes were also volumes evaluated, the MRI-based volumes are higher, these separately evaluated for the tumors of grades I/II and were significantly higher only in the higher-grade gliomas grades III/IV [Table 2]. Although for each of the four target (grades III/IV). J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 11 GTV on MRI (cc) CTV on MRI (cc) Number Number Datta, et al.: Delineation of target volumes in brain tumors DISCUSSION AND CONCLUSIONS −601 and +43% (mean ± SD: −106.7% ± 177.3) [Figure 2]. The corresponding percentage difference in GTV ranged Prior to the era of routine availability of CT and MRI, from −571 to 29% (mean ± SD: −62.6% ± 131.8). Such an postoperative management of malignant gliomas involved extent of uncertainty, with only CT-based planning, would be whole brain irradiation. Although, various clinical trials unacceptable and defeat any purposeful endeavour for dose showed a positive gain with postoperative radiotherapy in escalation studies using various state of the art technologies these patients, the need for accurate target localization was such as three-dimensional conformal radiotherapy, stereotactic perhaps not felt since the radiation portals were reasonably radiosurgery or radiotherapy, and intensity-modulated generous in covering the entire cranial contents. However, radiation therapy, all of which require accurate target [20] with the gradual acceptance of PBI for malignant gliomas, delineation. accuracy in target delineation needs to be ensured. The target should include the residual postoperative tumor and Apart from anatomical target definition of brain tumors a margin of usually 2-3 cm around the tumor to take care by contrast-enhanced CT and MRI, functional imaging of the possibility of microscopic disease infiltration into the using Tl-single emission photon spectroscopy (SPECT) adjoining brain parenchyma, which has been evident from and positron emission tomography (PET) has been able [8-13] various antemortem and postmortem studies. to highlight the metabolically active and viable tumor [21] tissues within the anatomical region. Even with the Definition of target volumes could be subjective, and a number use of conventional MRI techniques, the limitations for of studies have reported inter-observer and intra-observer demarcating the true spatial limits of tumor have been [14-19] variability. The present study has therefore not tried to investigated and proton magnetic spectroscopy has been [22] address this question of observer variability but attempted to explored to obtain information on tumor metabolism. highlight the importance of incorporation of target volumes A true representation of the target would nonetheless from multiple imaging modalities. be an anatometabolic fusion image obtained through [20,23] coregistration of images. Thus, the present image- The residual tumor volumes following surgery are perhaps guided radiotherapy techniques, aided by multimodality best evaluated in scans carried out at 24-48 h following imaging using contrast-enhanced CT, MRI, and possibly surgery, by which time it is possible to differentiate between SPECT/PET, could be expected to demonstrate an improved the enhancing residual tumor and the postoperative changes. survival as a result of more accurate target delineation, However, there are logistic problems involved in undertaking especially in certain good-prognosis subsets of patients of these scans within 24-48 h for defining the residual volume malignant gliomas. However, till such time as these imaging for radiation therapy. Most of these patients are still under facilities, along with appropriate co-registration software, the care of the neurosurgeons during this initial postoperative are available in most radiotherapy centers, routine RTP for period; the patient is usually referred for radiotherapy after brain tumors will be based either on contrast-enhanced CT histopathological confirmation and once he or she is fit to or MRI. be discharged from neurosurgery. Moreover, such scans for radiation treatment planning are done using immobilization Thus, to conclude, this study emphasizes the extent to casts and these can only be made after the wound has healed which the CT images of operated gliomas could result in and when there are no dressings on the scalp that could alter uncertainties in delineation of various ICRU-50 volumes, the skull contours. However, during the target delineation leading to significant geographical misses and target under on pre-radiotherapy CT/MRI images, all corresponding dosage, especially in the case of high-grade gliomas. Since all preoperative CT/MRI images are also reviewed. patients included in this study have been treated based on the MRI-derived volumes, it is not possible to say as to what The CTVs and GTVs in this study from both contrast-enhanced would have been the pattern of failures if these patients had CT and MRI were drawn out by an experienced neuroradiologist been treated on the basis of CT-derived volumes. However, in association with the radiation oncologist. Both these since most of the recurrences are known to be limited to the [2] volumes were depicted larger using MRI, the difference being volume in and around the T2-weighted images, it is necessary significantly more for the grade III and grade IV gliomas. that a proper delineation of targets based on the MRI images should be carried out to minimize the risks of geographical The implications of these volume differences could come into misses and, thereby, enable delivery of the intended doses play during RTP. Since these patients were usually planned to the target volumes. Further refinement of these target to receive a dose of 45 Gy to the CTV, followed by a boost volumes could be possible through the incorporation of the of 15 Gy to the postoperative residual GTV, a difference in various functional images; this possibility is being currently the corresponding volumes could result in an inadvertent investigated, with the hope that this would enable further geographical miss. Thus, in this group of 21 patients, the dose escalation to limited volumes of metabolically viable [24] percentage difference in CTV if outlined on CT, ranged between regions of the tumor. 12 J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 Datta, et al.: Delineation of target volumes in brain tumors Variability in target volume delineation for brain tumors. Radiother REFERENCES Oncol 1993;29:169-75. 15. Myrianthopoulos LC, Vijayakumar S, Spelbring DR, Krishnasamy S, 1. Berg G, Blomquist E, Cavallin-Ståhl E. A systematic overview of Blum S, Chen GT. Quantitation of treatment volumes from CT and MRI radiation therapy effects in brain tumors. Acta Oncol 2003;42:582-8. in high-grade gliomas: Implications for radiotherapy. Magn Reson 2. Jansen EP, Dewit LG, van Herk M, Bartelink H. Target volumes in Imaging 1992;10:375-83. radiotherapy for high-grade malignant glioma of the brain. Radiother 16. Ten Haken RK, Thornton AF Jr, Sandler HM, LaVigne ML, Quint DJ, Oncol 2000;56:151-6. 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Human cerebral gliomas:correlation resonance images using anatomical features. J Digit Imaging of postmortem MR imaging and neuropathologic findings. Radiology 2000;13:196-9. 1989;170:211-7. 24. Dhermain F, Ducreux D, Bidault F, Bruna A, Parker F, Roujeau T, 12. Kelly PJ, Daumas-Duport C, Kispert DB, Kall BA, Scheithauer BW, Illig JJ. et al. Use of the functional imaging modalities in radiation therapy Imaging based stereotactic serial biopsies in untreated intracranial treatment planning in patients with glioblastoma. Bull Cancer glial neoplasms. J Neurosurg 1987;66:865-74. 2005;92:333-42. 13. Watanabe M, Tanaka R, Takeda N. Magnetic resonance imaging and histopathology of cerebral gliomas. Neuroradiology 1992;34:463-9. 14. Leunens G, Menten J, Weltens C, Verstraete J, van der Schueren E. Source of Support: Nil, Confl ict of Interest: None declared. 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Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors

Journal of Cancer Research and TherapeuticsJan 1, 2008

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Journal of Cancer Research and Therapeutics January-March 2008 | Volume 4 | Issue 1 CONTENTS Editorial Criteria for deciding cost-effectiveness for expensive new anti-cancer agents Rajiv Sarin .............................................................................................................................................................1 Original Articles The effect of three mouthwashes on radiation-induced oral mucositis in patients with head and neck malignancies: A randomized control trial PD Kumar Madan, PS Sequeira, Kamalaksha Shenoy, Jayaram Shetty .............................................................3 Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors Niloy R Datta, Rajasekar David, Rakesh K Gupta, Punita Lal ..............................................................................9 Radiofrequency ablation of hepatic metastasis: Results of treatment in forty patients GK Rath, PK Julka, S Thulkar, DN Sharma, Amit Bahl, S Bhatnagar .................................................................14 Execution of mantle fi eld with multileaf collimator: A simple approach Ramachandran Prabhakar, Kunhi Parambath P Haresh, Pappiah S Sridhar, Macharla A Laviraj, Pramod K Julka, Goura K Rath ...........................................................................................................................18 Prognostic and diagnostic value of serum pseudocholinesterase, serum aspartate transaminase, and serum alinine transaminase in malignancies treated by radiotherapy Arun Chougule, Sofi a Hussain, Dwaraka Prasad Agarwal .................................................................................21 Review Article An overview on applications of optical spectroscopy in cervical cancers C Murali Krishna, GD Sockalingum, MS Vidyasagar, M Manfait, Donald J Fernanades, BM Vadhiraja, K Maheedhar .......................................................................................................................................................26 Case Reports Radiotherapy for management of skin cancers in fi brodysplasia ossifi cans progressiva: A case report and review of the literature John Antony Frew, Charles G Kelly ....................................................................................................................37 Sarcomatoid squamous cell carcinoma of uterine cervix: Pathology, imaging, and treatment Milind Kumar, Amit Bahl, Daya Nand Sharma, Shipra Agarwal, Dhanapathi Halanaik, Rakesh Kumar, Goura Kishore Rath ............................................................................................................................................39 Brief Communications Chest wall metastasis from hepatocellular carcinoma in the absence of a primary: An unusual presentation Kaustav Talapatra, Reena Engineer, Jai Prakash Agarwal, Shilpa Vyas, Shyam Kishore Shrivastava .............42 Endobronchial metastasis of follicular thyroid carcinoma presenting as hemoptysis: A case report RAS Kushwaha, Sanjay Kumar Verma, Sanjay Vineet Mahajan ........................................................................44 Accelerated partial breast irradiation: An advanced form of hypofractionation Ashwini Budrukkar ..............................................................................................................................................46 Coexistence of carcinoma breast and Paget’s disease of bone S Sundaraiya, PK Pradhan, A Gupta, M Jain, SK Mishra, BK Das .....................................................................48 Letter to Editor Dysplastic hematopoiesis and underlying dysthyroidism Riad Akoum, Michel Saade, Wafi c Tabbara, Emile Brihi, Marwan Masri, Khaled Habib, Gerard Abadjian ........50 Reviewers’ List, 2007 ..............................................................................................................................51 The copies of the journal to members of the association are sent by ordinary post. The editorial board, association or publisher will not be responsible for non-receipt of copies. If any of the members wish to receive the copies by registered post or courier, kindly contact the journal’s / publisher’s offi ce. If a copy returns due to incomplete, incorrect or changed address of a member on two consecutive occasions, the names of such members will be deleted from the mailing list of the journal. Providing complete, correct and up-to-date address is the responsibility of the members. Copies are sent to subscribers and members directly from the publisher’s address; it is illegal to acquire copies from any other source. If a copy is received for personal use as a member of the association/society, one cannot resale or give-away the copy for commercial or library use. J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 53 Free full text available from Original Article www.cancerjournal.net Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors ABSTRACT Niloy R Datta, Rajasekar David , Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) 2 Rakesh K Gupta , constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative Punita Lal evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, Department of Radiation along with its implications for postoperative radiotherapy of brain tumors. Oncology, Rajiv Gandhi Cancer Institute and Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were Research Centre, New delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence Delhi, Department studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the of Radiotherapy and Radiodiagnosis and mean CTV (mean ± SD: −62.92 ± 93.99 cc; P = 0.006) and GTV (mean ± SD: −21.08 ± 36.04 cc; P = 0.014). These differences Imaging, Sanjay Gandhi were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for Postgraduate Institute low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be of Medical Sciences, Lucknow, India −106.7% and −62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of For correspondence: Dr. N.R. Datta, brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in Department of Radiation the regions of peritumoral edema. Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, KEY WORDS: Brain tumor, radiation therapy, target volumes, treatment planning Rohini, New Delhi - 110 085, India. E-mail: nrdatta@ yahoo.com INTRODUCTION edema, and adjacent normal brain parenchyma. These targets are better demarcated through T1 [1,3,4] Postoperative irradiation for brain tumors is an contrast and T2-weighted MRI images. accepted adjuvant treatment, especially for the [1] higher grades of brain tumors. Radiation portals The International Commission on Radiation Units [5] are now restricted to partial brain irradiation (ICRU)-report 50, had proposed that various target (PBI) rather than whole brain. This is based on the volumes be delineated during the radiation therapy evidences showing similar patterns of recurrence planning. These included, primarily, the gross target [2] for both the treatment strategies. However, volume (GTV), representing the gross tumor, and with the use of PBI, it becomes important that the clinical target volume (CTV) for the microscopic the treatment portals be designed and placed to presence of disease surrounding the GTV . The outlining effectively include both residual tumor volume and of these target volumes could be based on the various the adjoining regions of brain parenchyma, which imaging studies, namely contrast-enhanced CT or are likely to harbour microscopic disease. MRI. Planning target volume (PTV), defined with a margin of usually 0.5 to 1 cm surrounding the GTV Computed tomography (CT) and magnetic resonance or CTV, would depend on the treatment setup errors imaging (MRI) have been the two cornerstones in during the entire course of radiation therapy as [2] the imaging of brain tumors. CT images provide estimated by individual departments. The present valuable electron density information which is study therefore, aims to carry out a comparative mandatory for radiation therapy dose calculations, quantitative evaluation of the postoperative GTVs but CT has its limitations as far as soft tissue and CTVs for brain tumors, as visualized either on contrast is concerned. This could lead to difficulty contrast-enhanced CT or MRI, in patients referred for in accurate delineation of the tumor, peritumoral postoperative adjuvant radiotherapy. J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 9 Datta, et al.: Delineation of target volumes in brain tumors MATERIALS AND METHODS Statistical analyses were performed using SPSS statistical software for Windows, version 9.0 (SPSS Inc. Chicago, IL, A total of 21 patients, histopathologically proven as glioma USA). (all grades) and referred for postoperative radiotherapy were considered for this prospective study. All these patients were RESULTS immobilized using ORFIT thermoplastic cast (ORFIT industries, Belgium) and taken up for contrast-enhanced CT and MRI with Patients were usually referred for postoperative radiotherapy the cast in situ. within 2-3 weeks of the surgical procedure. Following simulation, contrast-enhanced CT and MRI were carried out at close intervals. The mean interval between surgery and CT: The study was conducted with the patients immobilized postoperative CT was 29 days (median: 21 days) while with on the flat couch of the diagnostic CT unit (Picker 5500, Picker MRI it was 26 days (median: 21 days). The mean interval International Inc, USA). Following contrast, axial cuts were between CT and MRI was 3 days (median: 1 day). Most of the usually taken from the vertex to the base of the skull, with a patients had glioblastoma multiforme and had undergone field of view (FOV) of 240 mm and a matrix size of 512 × 512. tumor decompression. The demographic details are listed in These were transferred to the radiation therapy treatment Table 1. planning (RTP) workstation (Isis-3D, Technologie Diffusion, France). All the target volumes delineated in MRI were significantly larger than in CT [Tables 1 and 2]. The mean CTV, consisting of MRI: MRI scans were taken with the standard head coil (1.5 T, peritumoral edema volume, delineated in MRI was 180.93 cc Magnetom, Siemens, Germany). A custom-made Perspex™ (SD: ± 117.70) as compared to 118.01 cc (SD: ± 82.94) in CT base plate, which could fit into the standard head coil but studies. Similarly, the mean GTV, comprising hyperintense was similar to the one used during CT acquisition, was used regions in contrast-enhanced T1W MRI images, was for fixing the cast during MRI. The images from the vertex 71.64 cc (SD: ± 58.42), while it was 50.56 cc (SD: ± 37.21) in to the base of the skull were obtained with spin-echo (SE) [6] contrast-enhanced CT studies [Figure 1]. Compared to MRI, sequence, which has the least image distortions. The CT significantly underestimated the volumes, resulting conventional SE T2-weighted (TR/TE1, 2/n: 3000/12, 80/1), in a mean difference between the imaging modalities plain, and post-gadolinium contrast T1-weighted (1012/14/2) (CT volume − MRI volume) of −62.92 ± 93.99 cc (P = 0.006) axial MR images were obtained using a 256 × 256 matrix for CTV and −21.08 ± 36.04 cc (P = 0.014) for GTV [Table 2]. size, a bandwidth of 65 Hz/pixel, and an FOV of 250 mm. The percentage difference calculated taking the CT volume The MR images were transferred to the RTP workstation for as baseline [(CT-based volume − MRI-based volume)/ treatment planning. CT-based volume × 100] shows that for CTV and GTV, the mean percentage differences was −106.7% (SD: ± 177.3) and −62.6% Postoperative target volumes for residual GTV and CTV were (SD: ± 131.8), respectively [Figure 2]. drawn on contrast-enhanced CT and MRI images as per the [5] recommendations in ICRU report 50. Since all these patients had undergone prior surgery, ranging from just biopsy to Table 1: Patient demography (n = 21) subtotal resection, the residual GTV and the peritumoral Characteristics Distribution edema were estimated separately for each imaging modality. Age (in years) 42.2 ± 15.5* The details of the delineation of various postoperative target (range: 14-79) volumes, done by an experienced neuroradiologist along with Location of tumor Frontal:parietal:temporal:occipital 8:3:8:2 radiation oncologist on the postoperative contrast-enhanced Operative procedure CT and MRI, are as follows: Biopsy:DPN:STR 1:15:5 Histology Astrocytoma:oligoastrocytoma 19:2 For phase I treatment, CTV was marked on contrast-enhanced Tumor grade CT as regions of brain parenchyma showing hypodensity Grade I:II:III:IV 3:2:3:13 surrounding the residual tumor with any area of adjoining Tumor dose (Gy) 61.1 ± 4.7 mass effect. On MRI, the hyperintense region on T2W images (range: 50-66) Gross tumor volume (cc) was delineated as CTV. For the phase II treatment, the contrast- CT 50.57 ± 37.21 enhanced regions depicting a mass effect was considered (range: 4.22-146.72) as residual tumor (GTV) for both contrast-enhanced CT and MRI 71.64 ± 58.42 [7] T1W contrast studies. The actual volumes (in cc) for the (range: 9.78-253.97) Peritumoral edema volume (cc) corresponding CTVs and GTVs were noted from the RTP CT 118.01 ± 82.94 workstation in contrast-enhanced CT-based and MRI based (range: 12.43-295.55) plans. A total dose of 60 Gy was delivered in two phases: 45 Gy MRI 180.93 ± 117.70 to the CTV in phase I and 15 Gy, with reduced field sizes, to (range: 23.62-494.21) the GTV alone in phase II. *Mean ± standard deviation; DPN: Decompression; STR: Subtotal resection 10 J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 Datta, et al.: Delineation of target volumes in brain tumors Table 2: Mean difference in clinical target volumes and postoperative gross target volumes as evident on contrast-enhanced computed tomography and magnetic resonance imaging for (a) all patients, (b) grades I and II, and (c) grades III and IV Volume CECT-based (cc) (CECT) MRI-based (cc) (MRI) Difference (cc) CECT−MRI P-value* A: All patients (n = 21) CTV 118.01 ± 82.94 180.93 ± 117.70 −62.92 ± 93.99 0.006 GTV 50.57 ± 37.21 71.64 ± 58.42 −21.08 ± 36.04 0.014 B: Grades I and II (n = 5) CTV 116.37 ± 78.14 239.51 ± 178.09 −123.14 ± 117.93 0.080 GTV 50.07 ± 54.65 101.36 ± 98.10 −51.29 ± 57.63 0.117 C: Grades III and IV (n = 16) CTV 118.52 ± 86.84 162.62 ± 92.26 −44.10 ± 80.51 0.045 GTV 50.72 ± 32.39 62.35 ± 39.96 −11.63 ± 21.13 0.044 *Paired sample ‘t’ test; CTV: Clinical target volume; GTV: Postoperative residual gross target volume. All volumes indicate mean ± standard deviation 500 7 (a) (a) 1 0 50 100 150 200 250 300 350 400 450 500 0 -600 -500 -400 -300 -200 -100 0 CTV on CECT (cc) % difference (CTV) (b) 200 8 150 6 (b) 0 50 100 150 200 250 300 -550 -500 -450 -400 -350 -300 -250 -200 -150 -100 -50 0 50 GTV on CECT (cc) % difference (GTV) Figure 1: Scatter plot for the various ICRU report 50 volumes - clinical Figure 2: Histogram showing distribution of patients and percentage target volumes (CTV) and gross target volumes (GTV) - as estimated differences between contrast-enhanced CT and MRI for clinical target by contrast-enhanced CT and MRI studies. The curves Þ tted represent volumes (CTV) and gross target volumes (GTV). The normal distribution 2 2 linear Þ t. (a) CTV: r = 0.77, (b) GTV: r = 0.86. curve for the frequency distribution is also shown. (a) CTV (mean ± SD: −106.7% ± 177.3) and (b) GTV (mean ± SD: −62.6% ± 131.8). The differences in the various target volumes were also volumes evaluated, the MRI-based volumes are higher, these separately evaluated for the tumors of grades I/II and were significantly higher only in the higher-grade gliomas grades III/IV [Table 2]. Although for each of the four target (grades III/IV). J Cancer Res Ther - March 2008 - Volume 4 - Issue 1 11 GTV on MRI (cc) CTV on MRI (cc) Number Number Datta, et al.: Delineation of target volumes in brain tumors DISCUSSION AND CONCLUSIONS −601 and +43% (mean ± SD: −106.7% ± 177.3) [Figure 2]. The corresponding percentage difference in GTV ranged Prior to the era of routine availability of CT and MRI, from −571 to 29% (mean ± SD: −62.6% ± 131.8). Such an postoperative management of malignant gliomas involved extent of uncertainty, with only CT-based planning, would be whole brain irradiation. Although, various clinical trials unacceptable and defeat any purposeful endeavour for dose showed a positive gain with postoperative radiotherapy in escalation studies using various state of the art technologies these patients, the need for accurate target localization was such as three-dimensional conformal radiotherapy, stereotactic perhaps not felt since the radiation portals were reasonably radiosurgery or radiotherapy, and intensity-modulated generous in covering the entire cranial contents. However, radiation therapy, all of which require accurate target [20] with the gradual acceptance of PBI for malignant gliomas, delineation. accuracy in target delineation needs to be ensured. The target should include the residual postoperative tumor and Apart from anatomical target definition of brain tumors a margin of usually 2-3 cm around the tumor to take care by contrast-enhanced CT and MRI, functional imaging of the possibility of microscopic disease infiltration into the using Tl-single emission photon spectroscopy (SPECT) adjoining brain parenchyma, which has been evident from and positron emission tomography (PET) has been able [8-13] various antemortem and postmortem studies. to highlight the metabolically active and viable tumor [21] tissues within the anatomical region. Even with the Definition of target volumes could be subjective, and a number use of conventional MRI techniques, the limitations for of studies have reported inter-observer and intra-observer demarcating the true spatial limits of tumor have been [14-19] variability. The present study has therefore not tried to investigated and proton magnetic spectroscopy has been [22] address this question of observer variability but attempted to explored to obtain information on tumor metabolism. highlight the importance of incorporation of target volumes A true representation of the target would nonetheless from multiple imaging modalities. be an anatometabolic fusion image obtained through [20,23] coregistration of images. Thus, the present image- The residual tumor volumes following surgery are perhaps guided radiotherapy techniques, aided by multimodality best evaluated in scans carried out at 24-48 h following imaging using contrast-enhanced CT, MRI, and possibly surgery, by which time it is possible to differentiate between SPECT/PET, could be expected to demonstrate an improved the enhancing residual tumor and the postoperative changes. survival as a result of more accurate target delineation, However, there are logistic problems involved in undertaking especially in certain good-prognosis subsets of patients of these scans within 24-48 h for defining the residual volume malignant gliomas. However, till such time as these imaging for radiation therapy. Most of these patients are still under facilities, along with appropriate co-registration software, the care of the neurosurgeons during this initial postoperative are available in most radiotherapy centers, routine RTP for period; the patient is usually referred for radiotherapy after brain tumors will be based either on contrast-enhanced CT histopathological confirmation and once he or she is fit to or MRI. be discharged from neurosurgery. Moreover, such scans for radiation treatment planning are done using immobilization Thus, to conclude, this study emphasizes the extent to casts and these can only be made after the wound has healed which the CT images of operated gliomas could result in and when there are no dressings on the scalp that could alter uncertainties in delineation of various ICRU-50 volumes, the skull contours. However, during the target delineation leading to significant geographical misses and target under on pre-radiotherapy CT/MRI images, all corresponding dosage, especially in the case of high-grade gliomas. Since all preoperative CT/MRI images are also reviewed. patients included in this study have been treated based on the MRI-derived volumes, it is not possible to say as to what The CTVs and GTVs in this study from both contrast-enhanced would have been the pattern of failures if these patients had CT and MRI were drawn out by an experienced neuroradiologist been treated on the basis of CT-derived volumes. However, in association with the radiation oncologist. Both these since most of the recurrences are known to be limited to the [2] volumes were depicted larger using MRI, the difference being volume in and around the T2-weighted images, it is necessary significantly more for the grade III and grade IV gliomas. that a proper delineation of targets based on the MRI images should be carried out to minimize the risks of geographical The implications of these volume differences could come into misses and, thereby, enable delivery of the intended doses play during RTP. Since these patients were usually planned to the target volumes. Further refinement of these target to receive a dose of 45 Gy to the CTV, followed by a boost volumes could be possible through the incorporation of the of 15 Gy to the postoperative residual GTV, a difference in various functional images; this possibility is being currently the corresponding volumes could result in an inadvertent investigated, with the hope that this would enable further geographical miss. 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