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Comparison of supine and prone craniospinal irradiation in children with medulloblastoma
PRRO-00350; No of Pages 6 Practical Radiation Oncology (2014) xx, xxx–xxx
www.practicalradonc.org
Original Report
Comparison of supine and prone craniospinal irradiation in children with medulloblastoma Jonathan Verma MD a , Ali Mazloom MD a , Bin S. Teh MD a , Michael South CMD a , E. Brian Butler MD a , Arnold C. Paulino MD a, b,⁎ a
Department of Radiation Oncology, The Methodist Hospital, Houston, Texas Department of Pediatrics, Division of Pediatric Hematology/Oncology, Texas Children’s Hospital, Houston, Texas
b
Received 31 March 2014; revised 6 May 2014; accepted 16 May 2014
Abstract Purpose: To compare port film rejection and treatment outcome according to craniospinal irradiation (CSI) position for medulloblastoma. Methods and materials: We retrospectively searched for patients ≤ 19 years treated with CSI for medulloblastoma at 1 department. We collected the following data: age; sex; risk group; need for general anesthesia; radiation therapy (RT) dose and fractionation; and the acceptance or rejection of weekly port films during treatment. We also collected data on outcomes, including neuraxis recurrence and possible complications such as myelitis. Results: Of 46 children identified, 23 were treated prone (median age, 8.1 years) and 23 supine (median age, 7.2 years). High-risk disease was seen in 26% of prone and 35% of supine patients (P = .25). There was no difference in use of general anesthesia between those treated prone versus supine (57% vs 61%). The rejection rate of cranial port films in the prone position was 35%, which was significantly higher than the rate of 8% in patients treated supine (P b .0001). The 5-year progression-free (P = .37) and overall survival (P = .18) rates were 62% and 67% for prone and 76% and 84% for supine patients. There were no isolated junctional failures or radiation myelitis in either CSI position. Conclusions: The supine position for CSI was found to have similar survival outcomes compared with the prone position. A higher proportion of rejected cranial port films was seen in children treated in the prone position. © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction
Portions of this work were presented at the 54th Annual Meeting of the American Society for Radiation Oncology (ASTRO), Boston, MA, October 28-31, 2012. Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology, 1515 Holcombe Blvd, Box 97, Houston, TX 77030. E-mail address: [email protected] (A.C. Paulino).
Medulloblastoma accounts for approximately 15%-20% of all pediatric central nervous system (CNS) tumors. The treatment of medulloblastoma requires a multimodality approach and includes surgical resection, radiation therapy (RT), and chemotherapy. Advances in therapy have resulted in 5-year survival rates of 70%-80%. 1-3 Radiation therapy for medulloblastoma consists of craniospinal irradiation (CSI) followed by a boost to the
http://dx.doi.org/10.1016/j.prro.2014.05.004 1879-8500/© 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
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posterior fossa or tumor bed. Traditionally, the craniospinal axis has been treated with the patients in the prone position, using an arrangement of opposed lateral beams to treat the cranium, abutted to 1 or 2 posteroanterior beams to treat the spine. 4 The major advantage for treatment in this position is the ability for the physician and the therapist to directly visualize the match lines between the cranial and spinal junction as well as the spinal to spinal junctions which is separated by a skin gap. Visualization prior to each treatment ensures that overdosage or underdosage to the underlying spinal cord and thecal sac at the junction sites is minimized. Another possible advantage is the ability for the therapist to visualize the spinal field and palpate the spine to make sure the spine is straight. However, there are also several limitations to treating in the prone position. The position can be uncomfortable for the patient, particularly a young child. Airway access, necessary in patients requiring anesthesia, can be difficult for anesthesiologists in patients who are prone. Finally, positioning patients prone can be labor-intensive for the therapist especially if the patient is large. For these reasons, several institutions, including ours, have used a supine technique to deliver CSI. 5-8 Because we have experience treating medulloblastoma patients in the supine and prone positions, we conducted a retrospective review of our experience with special emphasis on port film verification and treatment outcome with each approach.
prone position has been described previously. 4 Opposed lateral beams were used to treat the cranial fields, which abutted the posterior spinal field. The divergence of the cranial and spinal fields was corrected for by rotating the collimator and rotating the treatment table. For patients who required 2 posterior spinal fields, a skin gap was calculated to minimize overdosage and underdosage at the spinal to spinal junction. Patients had junction shifts every 5 treatments during the RT course. After July 2004, patients were treated in the supine position. Our technique for supine CSI has been described in detail previously. 5 The patients were positioned supine on a low-density treatment board and immobilized with the use of a 5-point thermoplastic mask and immobilization bag. Opposed lateral beams were used to treat the cranial fields and were abutted to a posteroanterior spinal beam, with the divergence of the beams at the junction corrected for by rotating the collimator and treatment table. A second beam was used to treat the spine when necessary. The treatment table was rotated 90 degrees and the gantry positioned to match the divergence of the beams at the spinal-spinal junction. Patients who received supine CSI were treated with intrafractional junction shifts using 3 multileaf collimator control points. This technique has the advantage of reducing the excess dose to the junction if an inadvertent overlap was to occur; or conversely, reducing the amount of underdosage if there is an inadvertent gap at the junction. 5
Methods and materials
Review of films
We searched our institutional database for patients ≤ 19 years of age who were treated for medulloblastoma with CSI at 1 department between 1999 and 2011. We collected the following data: age; sex; risk group; need for general anesthesia; anesthesia complications; and RT dose and fractionation. We also collected data on outcomes, including neuraxis recurrence and possible complications such as myelitis.
Weekly port films were taken during the course of treatment to verify patient positioning. Because radiation oncologists’ standards for rejection of port films may have differed during the study period, all port films were retrospectively reviewed by both J.V. and A.C.P. and a classification of accepted or rejected port films was made. Data on the proportion of films that were rejected and the reasons for rejection were recorded and analyzed. Cranial port films were evaluated to ensure that at least a 0.5 cm inferior margin was covering the cribriform plate and the skull base. In cases where the margin inferior to the cribriform plate or base of skull was b 0.5 cm, the film was classified a rejected film. Films of the spine were reviewed to ensure that the spine was straight and midline in the treatment field. The spine field port film was rejected if the edge of the field laterally was b 0.5 cm from the ipsilateral edge of the vertebral body. Proper junction matching was evaluated on port films with the aid of radiopaque wires placed at the junction sites.
Radiation therapy Radiation therapy consisted of CSI plus a boost to either the posterior fossa or the tumor bed. Standard-risk patients were treated using a dose of 23.4 Gy to the craniospinal axis, and high-risk patients using a dose of 36-39.6 Gy. All patients received a boost to the posterior fossa or tumor bed totaling 54-55.8 Gy. All patients were treated with daily fractions of 1.8 Gy. All patients received chemotherapy after the entire RT course. Patients treated prior to July 2004 were treated in the prone position. The patient’s head was immobilized using a customized thermoplastic mask that was attached to a face-holder, which was in contact with the patient’s forehead and chin. The technique for treatment in the
Statistical analysis Kaplan-Meier analysis and the log-rank test were used to assess the statistical significance of progression-free and
Practical Radiation Oncology: Month 2014
overall survival. The Fisher exact test was used to determine differences in patient, tumor, and treatment characteristics between supine and prone CSI.
Results Our search identified 46 eligible patients, including 23 (50%) who had been treated prone and 23 (50%) treated supine. The median age was 8.1 years (range, 3.3-18 years) in patients treated prone, and 7.2 years (range, 3-19 years) in those treated supine. Fourteen patients (31%) were categorized as high risk based on either residual disease greater than 1.5 cm 2 or M + disease; this included 26% of those treated prone and 35% of those treated supine (P = .25). The remaining patients were standard risk. The median follow-up for surviving patients was 76 months (range, 4-153 months).
General anesthesia use Because of the young age of some patients as well as the complexity of treatment setup and delivery, general anesthesia was employed in 27 (59%) children. Thirteen were treated prone while the rest were treated supine during the RT course. There was no difference in use of general anesthesia between those treated prone versus supine (57% vs 61%, P = 1.0). No complications were noted either in the prone or supine position in children requiring general anesthesia.
Review of port films There were a total of 399 port films available for review. Rejection rates for cranial, upper, lower, and entire spine films are shown in Table 1. The rejection rate of cranial port films in the prone position was 35% (27/78), which was significantly higher than the rate of 8% in patients treated supine (6/73, P b .0001). The rejection rates for cranial port films in the prone position were 43%, 24%, and 30% for weeks 1, 2, and 3, respectively. The rejection rates in patients treated supine were 13%, 9%, and 0% for the same weeks of treatment. The difference reached statistical significance for week 1 (P = .02) and week 3 (P b .01). The most common reason for rejection of cranial port films was to correct head tilt to improve coverage at the cribriform plate and the inferior temporal lobe. The rejection rate of upper spine port films was 21% (16/75) in patients treated prone and 32% (23/71) in those treated supine (P = .14). The rejection rates of upper spine films for weeks 1, 2, and 3 were 22%, 29%, and 25% for those treated prone, while the rates were 30%, 30%, and 45% for patients treated supine. The difference was not statistically significant for any week of treatment.
Supine vs prane craniospinal irradiation Table 1 position
3
Port film rejection rates according to craniospinal
Radiation therapy field
Prone
Supine
P value
Cranium 27/78 (35%) 6/73 Upper spine 16/75 (21%) 23/71 Lower spine 8/60 (13%) 8/42 Upper + lower spine 24/135 (18%) 31/113
(8%) b .0001 (32%) .14 (16%) .41 (27%) .09
Thirteen percent (8/60) of prone lower spine films were rejected, compared with 19% (8/42) of supine films (P = .41). The proportions in weeks 1, 2, and 3 for patients treated prone were 5%, 17%, and 13%, while the rates for supine were 15%, 30%, and 14%; the difference did not reach significance for any week of treatment. When the upper and lower spine films were combined together and rejection rates compared between the supine and prone positions, there was no statistically significant difference. A total of 27% (31/113) films of the spine were rejected in the supine position versus 18% (24/135) in the prone position (P = .09). The most common reasons for rejection of spine films were to reposition the patient laterally or straighten the spine in the treatment field. We also compared the concordance of rejection cranial and spinal films between the original treatment and the retrospective review. Concordance was found in 150 of 151 (99.3%) of cranial and 238 of 248 (96%) of spinal fields. Examples of rejected cranial and upper spinal films are shown in Fig 1A and B, respectively. Finally, to investigate the influence of increased familiarity with setup technique on the positioning, the rejection rates were compared between the first half of patients treated and the second half treated with each technique. No significant difference was found in either the supine (P = .69) or prone (P = .14) positions.
Progression-free survival, patterns of failure, and overall survival There was no difference in 5-year progression-free survival between patients treated supine or prone (Fig 2). The 5-year progression-free survival for all patients was 69% and was not significantly different between patients treated supine (76%) and those treated prone (62%, P = .37). A total of 13 patients developed recurrent disease, including 8 (35%) in the prone group and 5 (22%) of the supine group. There was no case of isolated junctional relapse. Two patients had simultaneous recurrence in the brain and in the spinal cord close to a junction site; 1 had been treated supine and the other treated prone. Three had recurrence in the brain and spine but not close to a junction site. The remaining recurrences were as follows: 3 patients recurred in the tumor bed; 2 in the supratentorial brain; 1 in the nontumor bed posterior fossa, and 2 elsewhere in the nonjunction spinal axis.
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Figure 1 Examples of rejected port films. (A) Cranial field; the blocked edge of the field needs to be at least 0.5 cm from the cribriform plate and infratemporal fossa. The blue line is the uncorrected while the red line is the corrected treatment field. Note that the lower border of the cranial field exits at the chin, thus the spine field for this patient will exit through the oral cavity. This might be best avoided using supine craniospinal irradiation, where the neck can be better hyperextended. (B) Spinal field; the lateral edge of the field has to be at least 0.5 cm from the ipsilateral vertebral body. The blue line indicates the uncorrected borders of the upper spine field. The spine is not in the middle of the field. Also, the width of the spine field is generous and can be smaller. (For color version, see online at www. practicalradonc.org).
There was no significant difference in 5-year overall survival between patients treated prone or supine. The 5-year overall survival was 75% for all patients, 84% in those treated supine and 67% in those treated prone (P = .18).
Radiation myelopathy There was no case of radiation myelitis documented in patients treated supine or prone.
Discussion Although several authors have described their technique for supine craniospinal irradiation, to our knowledge this is the first study to compare both port film rejection rates and survival between patients treated prone and supine for medulloblastoma. Our data suggest that more cranial port films are rejected in children treated prone. There was no difference in use or complications of general anesthesia, progression-free or overall survival, junctional recurrences, and radiation myelitis according to treatment position. Craniospinal irradiation in the supine position offers several advantages compared with treatment in the prone position, including patient comfort and ease of airway access. Klosky et al 9 conducted a prospective study evaluating medical, psychosocial, and demographic factors
related to pediatric distress during radiation therapy; the authors concluded that patients treated supine experienced significantly smaller changes in heart rate and behavioral distress compared with patients treated prone. In fact, treatment position (prone vs supine) was the only variable that reached statistical significance for these outcomes in their analysis. They attributed part of the increase in behavioral distress to the more limited field of vision during the procedure when patients are prone. In another study, 12 adult patients were positioned prone and supine for CSI. The supine position was considered more comfortable by patients based on a questionnaire. 6 Treatment in the prone position has implications on the physiology and potential complications associated with the use of anesthesia. Airway access can be difficult with the patient prone, and, although rare, there are reports of obstruction from secretions in the prone position. 10 The prone position is also associated with a decreased cardiac index, altered lung volume, and altered distribution of ventilation and pulmonary blood flow. 11 Finally, although rare, there are reports of direct and indirect pressure injuries to structures including the skin, trachea, and mediastinum, most commonly in patients with structural abnormalities predisposing them to complications. 12,13 The risk of these complications, although small, could be mitigated by treatment in the supine position. We did not have any anesthesia complication with either treatment position.
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Figure 2 Progression-free survival of patients with medulloblastoma treated with supine and prone craniospinal irradiation, P = .37.
Our results suggest that the supine position is also more reproducible with respect to the cranial fields than the prone position. In particular, there were fewer instances of correction for head tilt in patients treated supine. The main reason is better immobilization of the head in the supine position; in the prone position, the chin can tilt with the face mask. We are also able to use the 5-point mask in the supine position, which immobilizes the neck better. When treating the cranial fields in medulloblastoma, it is of critical importance to ensure adequate coverage of the cribriform plate and the inferior temporal lobes. The cribriform plate may inadvertently be partially spared by shielding intended to protect the eye due to its close proximity, and there are several studies describing recurrences in this region after inadequate coverage. 14,15 The most common reason for rejection of spine port films was to reposition the patient so that the spine is straight in the center of the treatment field. With the patient prone, the clinician and therapist can directly visualize the entry of the spinal beam and palpate the spine, ensuring that it is midline in the field. This is not possible with the supine patient, which may explain the higher number of rejected port films in our patients treated supine, with the difference being not statistically significant. Traditionally, craniospinal irradiation has been delivered with the patient prone because of the ability to easily visualize the entry of the beams. The calculation and measurement of a skin gap between spinal beams also offers added reassurance that there is no overlap in the divergence of the beams, which could put the patient at risk for radiation myelitis; or underdosage due to an inadvertently large gap, which could put the patient at risk for a junctional recurrence. In our study we found no cases of isolated junctional relapse or radiation myelitis. In addition, we found no difference in progression-free or overall survival between patients treated supine or prone. Our technique of utilizing daily intrafractional junction shifts means that if an inadvertent overlap occurred due to setup error, the overlap
Supine vs prane craniospinal irradiation
5
would result in a lower fractional dose to the overlap region rather than a doubling of the dose that would occur if the junction was shifted between, rather than within, fractions. Because dose per fraction is an important factor in the development of late effects such as radiation myelopathy, we believe that using intrafractional junction shifts reduces the risk of this late complication. 16 Our results indicate that craniospinal irradiation can be performed safely in the supine position without compromising outcomes. There is an inherent bias in doing a retrospective comparison of patient positioning during CSI. The supine patients were treated in the more “modern era” of radiation therapy when there have been improvements in immobilization and imaging technology. Furthermore, therapists performing CSI setup become more experienced with time. For this reason, we compared the first half to the second half of patients treated with each technique to see if there was a difference in rejected port films. There was no difference in port film rejection rates over time in children treated prone or supine. To remove the possible bias introduced by different physicians checking port films, we (J.V. and A.C.P.) retrospectively reviewed each port film and gave a designation of accepted or rejected, which may not necessarily be the same as the original designation by the treating physician. Despite these limitations, we believe that this paper adds to the very limited literature regarding longterm survival outcome of patients treated in the supine position. To our knowledge, there has only been 1 report with long-term follow-up which shows that supine CSI has the same disease-free survival as prone CSI. 17 This paper also clinically validates previous methodologic reports of administering supine CSI. 5,8,18,19 In conclusion, our study shows that supine craniospinal irradiation in children with medulloblastoma does not compromise progression-free survival, or overall survival. Rejected port films in the cranium were more common with the prone position. There were no instances of radiation myelopathy in both the supine and prone CSI patients.
References 1. Packer RJ, Gajjar A, Vezina G, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24: 4202-4208. 2. Paulino AC, Mazloom A, Teh BS, et al. Local control after craniospinal irradiation, intensity-modulated radiotherapy boost, and chemotherapy in childhood medulloblastoma. Cancer. 2011;117:635-641. 3. Paulino AC. Current multimodality management of medulloblastoma. Curr Probl Cancer. 2002;26:317-356. 4. Paulino AC. Radiotherapeutic management of medulloblastoma. Oncology (Williston Park). 1997;11:818-823. 5. South M, Chiu JK, Teh BS, et al. Supine craniospinal irradiation using intrafractional junction shifts and field-in-field dose shaping. Early experience at Methodist Hospital. Int J Radiat Oncol Biol Phys. 2008;71:477-483. 6. Hideghéty K, Cserháti A, Nagy Z, et al. A prospective study of supine versus prone positioning and whole-body thermoplastic mask
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7.
8.
9.
10.
11.
12.
J. Verma et al fixation for craniospinal radiotherapy in adult patients. Radiother Oncol. 2012;102:214-218. Hawkins RB. A simple method of radiation treatment of craniospinal fields with patient supine. Int J Radiat Oncol Biol Phys. 2001;49:261-264. Huang F, Parker W, Freeman CR. Feasibility and early outcomes of supine-position craniospinal irradiation. Pediatr Blood Cancer. 2010;54: 322-325. Klosky JL, Tyc VL, Tong X, et al. Predicting pediatric distress during radiation therapy procedures: The role of medical, psychosocial, and demographic factors. Pediatrics. 2007;119:e1159-e1166. Grimmett WG, Poh J. Clearance of an obstructed endotracheal tube with an arterial embolectomy catheter with the patient in the prone position. Anaesth Intensive Care. 1998;26:579-581. Anderton JM. The prone position for the surgical patient: A historical review of the principles and hazards. Br J Anaesth. 1991;67:452-463. Bagshaw ON, Jardine A. Cardiopulmonary complications during anaesthesia and surgery for severe thoracic lordoscoliosis. Anaesthesia. 1995;50:890-892.
Practical Radiation Oncology: Month 2014 13. Rittoo DB, Morris P. Tracheal occlusion in the prone position in an intubated patient with Duchenne muscular dystrophy. Anaesthesia. 1995;50:719-721. 14. Carrie C, Hoffstetter S, Gomez F, et al. Impact of targeting deviations on outcome in medulloblastoma: Study of the French Society of Pediatric Oncology (SFOP). Int J Radiat Oncol Biol Phys. 1999;45:435-439. 15. Jereb B, Krishnaswami S, Reid A, Allen JC. Radiation for medulloblastoma adjusted to prevent recurrence to the cribriform plate region. Cancer. 1984;54:602-604. 16. Schultheiss TE, Higgins EM, El-Mahdi AM. The latent period in clinical radiation myelopathy. Int J Radiat Oncol Biol Phys. 1984;10:1109-1115. 17. Slampa P, Pavelka Z, Dusek L, et al. Longterm treatment results of childhood medulloblastoma by craniospinal irradiation in supine position. Neoplasma. 2007;54:62-67. 18. Michalski JM, Klein EE, Gerber R. Method to plan, administer, and verify supine craniospinal irradiation. J Appl Clin Med Phys. 2002;3: 310-316. 19. Thomadsen B, Mehta M, Howard S, Das R. Craniospinal treatment with the patient supine. Med Dosim. 2003;28:35-38.
www.practicalradonc.org
Original Report
Comparison of supine and prone craniospinal irradiation in children with medulloblastoma Jonathan Verma MD a , Ali Mazloom MD a , Bin S. Teh MD a , Michael South CMD a , E. Brian Butler MD a , Arnold C. Paulino MD a, b,⁎ a
Department of Radiation Oncology, The Methodist Hospital, Houston, Texas Department of Pediatrics, Division of Pediatric Hematology/Oncology, Texas Children’s Hospital, Houston, Texas
b
Received 31 March 2014; revised 6 May 2014; accepted 16 May 2014
Abstract Purpose: To compare port film rejection and treatment outcome according to craniospinal irradiation (CSI) position for medulloblastoma. Methods and materials: We retrospectively searched for patients ≤ 19 years treated with CSI for medulloblastoma at 1 department. We collected the following data: age; sex; risk group; need for general anesthesia; radiation therapy (RT) dose and fractionation; and the acceptance or rejection of weekly port films during treatment. We also collected data on outcomes, including neuraxis recurrence and possible complications such as myelitis. Results: Of 46 children identified, 23 were treated prone (median age, 8.1 years) and 23 supine (median age, 7.2 years). High-risk disease was seen in 26% of prone and 35% of supine patients (P = .25). There was no difference in use of general anesthesia between those treated prone versus supine (57% vs 61%). The rejection rate of cranial port films in the prone position was 35%, which was significantly higher than the rate of 8% in patients treated supine (P b .0001). The 5-year progression-free (P = .37) and overall survival (P = .18) rates were 62% and 67% for prone and 76% and 84% for supine patients. There were no isolated junctional failures or radiation myelitis in either CSI position. Conclusions: The supine position for CSI was found to have similar survival outcomes compared with the prone position. A higher proportion of rejected cranial port films was seen in children treated in the prone position. © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction
Portions of this work were presented at the 54th Annual Meeting of the American Society for Radiation Oncology (ASTRO), Boston, MA, October 28-31, 2012. Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology, 1515 Holcombe Blvd, Box 97, Houston, TX 77030. E-mail address: [email protected] (A.C. Paulino).
Medulloblastoma accounts for approximately 15%-20% of all pediatric central nervous system (CNS) tumors. The treatment of medulloblastoma requires a multimodality approach and includes surgical resection, radiation therapy (RT), and chemotherapy. Advances in therapy have resulted in 5-year survival rates of 70%-80%. 1-3 Radiation therapy for medulloblastoma consists of craniospinal irradiation (CSI) followed by a boost to the
http://dx.doi.org/10.1016/j.prro.2014.05.004 1879-8500/© 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
2
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Practical Radiation Oncology: Month 2014
posterior fossa or tumor bed. Traditionally, the craniospinal axis has been treated with the patients in the prone position, using an arrangement of opposed lateral beams to treat the cranium, abutted to 1 or 2 posteroanterior beams to treat the spine. 4 The major advantage for treatment in this position is the ability for the physician and the therapist to directly visualize the match lines between the cranial and spinal junction as well as the spinal to spinal junctions which is separated by a skin gap. Visualization prior to each treatment ensures that overdosage or underdosage to the underlying spinal cord and thecal sac at the junction sites is minimized. Another possible advantage is the ability for the therapist to visualize the spinal field and palpate the spine to make sure the spine is straight. However, there are also several limitations to treating in the prone position. The position can be uncomfortable for the patient, particularly a young child. Airway access, necessary in patients requiring anesthesia, can be difficult for anesthesiologists in patients who are prone. Finally, positioning patients prone can be labor-intensive for the therapist especially if the patient is large. For these reasons, several institutions, including ours, have used a supine technique to deliver CSI. 5-8 Because we have experience treating medulloblastoma patients in the supine and prone positions, we conducted a retrospective review of our experience with special emphasis on port film verification and treatment outcome with each approach.
prone position has been described previously. 4 Opposed lateral beams were used to treat the cranial fields, which abutted the posterior spinal field. The divergence of the cranial and spinal fields was corrected for by rotating the collimator and rotating the treatment table. For patients who required 2 posterior spinal fields, a skin gap was calculated to minimize overdosage and underdosage at the spinal to spinal junction. Patients had junction shifts every 5 treatments during the RT course. After July 2004, patients were treated in the supine position. Our technique for supine CSI has been described in detail previously. 5 The patients were positioned supine on a low-density treatment board and immobilized with the use of a 5-point thermoplastic mask and immobilization bag. Opposed lateral beams were used to treat the cranial fields and were abutted to a posteroanterior spinal beam, with the divergence of the beams at the junction corrected for by rotating the collimator and treatment table. A second beam was used to treat the spine when necessary. The treatment table was rotated 90 degrees and the gantry positioned to match the divergence of the beams at the spinal-spinal junction. Patients who received supine CSI were treated with intrafractional junction shifts using 3 multileaf collimator control points. This technique has the advantage of reducing the excess dose to the junction if an inadvertent overlap was to occur; or conversely, reducing the amount of underdosage if there is an inadvertent gap at the junction. 5
Methods and materials
Review of films
We searched our institutional database for patients ≤ 19 years of age who were treated for medulloblastoma with CSI at 1 department between 1999 and 2011. We collected the following data: age; sex; risk group; need for general anesthesia; anesthesia complications; and RT dose and fractionation. We also collected data on outcomes, including neuraxis recurrence and possible complications such as myelitis.
Weekly port films were taken during the course of treatment to verify patient positioning. Because radiation oncologists’ standards for rejection of port films may have differed during the study period, all port films were retrospectively reviewed by both J.V. and A.C.P. and a classification of accepted or rejected port films was made. Data on the proportion of films that were rejected and the reasons for rejection were recorded and analyzed. Cranial port films were evaluated to ensure that at least a 0.5 cm inferior margin was covering the cribriform plate and the skull base. In cases where the margin inferior to the cribriform plate or base of skull was b 0.5 cm, the film was classified a rejected film. Films of the spine were reviewed to ensure that the spine was straight and midline in the treatment field. The spine field port film was rejected if the edge of the field laterally was b 0.5 cm from the ipsilateral edge of the vertebral body. Proper junction matching was evaluated on port films with the aid of radiopaque wires placed at the junction sites.
Radiation therapy Radiation therapy consisted of CSI plus a boost to either the posterior fossa or the tumor bed. Standard-risk patients were treated using a dose of 23.4 Gy to the craniospinal axis, and high-risk patients using a dose of 36-39.6 Gy. All patients received a boost to the posterior fossa or tumor bed totaling 54-55.8 Gy. All patients were treated with daily fractions of 1.8 Gy. All patients received chemotherapy after the entire RT course. Patients treated prior to July 2004 were treated in the prone position. The patient’s head was immobilized using a customized thermoplastic mask that was attached to a face-holder, which was in contact with the patient’s forehead and chin. The technique for treatment in the
Statistical analysis Kaplan-Meier analysis and the log-rank test were used to assess the statistical significance of progression-free and
Practical Radiation Oncology: Month 2014
overall survival. The Fisher exact test was used to determine differences in patient, tumor, and treatment characteristics between supine and prone CSI.
Results Our search identified 46 eligible patients, including 23 (50%) who had been treated prone and 23 (50%) treated supine. The median age was 8.1 years (range, 3.3-18 years) in patients treated prone, and 7.2 years (range, 3-19 years) in those treated supine. Fourteen patients (31%) were categorized as high risk based on either residual disease greater than 1.5 cm 2 or M + disease; this included 26% of those treated prone and 35% of those treated supine (P = .25). The remaining patients were standard risk. The median follow-up for surviving patients was 76 months (range, 4-153 months).
General anesthesia use Because of the young age of some patients as well as the complexity of treatment setup and delivery, general anesthesia was employed in 27 (59%) children. Thirteen were treated prone while the rest were treated supine during the RT course. There was no difference in use of general anesthesia between those treated prone versus supine (57% vs 61%, P = 1.0). No complications were noted either in the prone or supine position in children requiring general anesthesia.
Review of port films There were a total of 399 port films available for review. Rejection rates for cranial, upper, lower, and entire spine films are shown in Table 1. The rejection rate of cranial port films in the prone position was 35% (27/78), which was significantly higher than the rate of 8% in patients treated supine (6/73, P b .0001). The rejection rates for cranial port films in the prone position were 43%, 24%, and 30% for weeks 1, 2, and 3, respectively. The rejection rates in patients treated supine were 13%, 9%, and 0% for the same weeks of treatment. The difference reached statistical significance for week 1 (P = .02) and week 3 (P b .01). The most common reason for rejection of cranial port films was to correct head tilt to improve coverage at the cribriform plate and the inferior temporal lobe. The rejection rate of upper spine port films was 21% (16/75) in patients treated prone and 32% (23/71) in those treated supine (P = .14). The rejection rates of upper spine films for weeks 1, 2, and 3 were 22%, 29%, and 25% for those treated prone, while the rates were 30%, 30%, and 45% for patients treated supine. The difference was not statistically significant for any week of treatment.
Supine vs prane craniospinal irradiation Table 1 position
3
Port film rejection rates according to craniospinal
Radiation therapy field
Prone
Supine
P value
Cranium 27/78 (35%) 6/73 Upper spine 16/75 (21%) 23/71 Lower spine 8/60 (13%) 8/42 Upper + lower spine 24/135 (18%) 31/113
(8%) b .0001 (32%) .14 (16%) .41 (27%) .09
Thirteen percent (8/60) of prone lower spine films were rejected, compared with 19% (8/42) of supine films (P = .41). The proportions in weeks 1, 2, and 3 for patients treated prone were 5%, 17%, and 13%, while the rates for supine were 15%, 30%, and 14%; the difference did not reach significance for any week of treatment. When the upper and lower spine films were combined together and rejection rates compared between the supine and prone positions, there was no statistically significant difference. A total of 27% (31/113) films of the spine were rejected in the supine position versus 18% (24/135) in the prone position (P = .09). The most common reasons for rejection of spine films were to reposition the patient laterally or straighten the spine in the treatment field. We also compared the concordance of rejection cranial and spinal films between the original treatment and the retrospective review. Concordance was found in 150 of 151 (99.3%) of cranial and 238 of 248 (96%) of spinal fields. Examples of rejected cranial and upper spinal films are shown in Fig 1A and B, respectively. Finally, to investigate the influence of increased familiarity with setup technique on the positioning, the rejection rates were compared between the first half of patients treated and the second half treated with each technique. No significant difference was found in either the supine (P = .69) or prone (P = .14) positions.
Progression-free survival, patterns of failure, and overall survival There was no difference in 5-year progression-free survival between patients treated supine or prone (Fig 2). The 5-year progression-free survival for all patients was 69% and was not significantly different between patients treated supine (76%) and those treated prone (62%, P = .37). A total of 13 patients developed recurrent disease, including 8 (35%) in the prone group and 5 (22%) of the supine group. There was no case of isolated junctional relapse. Two patients had simultaneous recurrence in the brain and in the spinal cord close to a junction site; 1 had been treated supine and the other treated prone. Three had recurrence in the brain and spine but not close to a junction site. The remaining recurrences were as follows: 3 patients recurred in the tumor bed; 2 in the supratentorial brain; 1 in the nontumor bed posterior fossa, and 2 elsewhere in the nonjunction spinal axis.
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Figure 1 Examples of rejected port films. (A) Cranial field; the blocked edge of the field needs to be at least 0.5 cm from the cribriform plate and infratemporal fossa. The blue line is the uncorrected while the red line is the corrected treatment field. Note that the lower border of the cranial field exits at the chin, thus the spine field for this patient will exit through the oral cavity. This might be best avoided using supine craniospinal irradiation, where the neck can be better hyperextended. (B) Spinal field; the lateral edge of the field has to be at least 0.5 cm from the ipsilateral vertebral body. The blue line indicates the uncorrected borders of the upper spine field. The spine is not in the middle of the field. Also, the width of the spine field is generous and can be smaller. (For color version, see online at www. practicalradonc.org).
There was no significant difference in 5-year overall survival between patients treated prone or supine. The 5-year overall survival was 75% for all patients, 84% in those treated supine and 67% in those treated prone (P = .18).
Radiation myelopathy There was no case of radiation myelitis documented in patients treated supine or prone.
Discussion Although several authors have described their technique for supine craniospinal irradiation, to our knowledge this is the first study to compare both port film rejection rates and survival between patients treated prone and supine for medulloblastoma. Our data suggest that more cranial port films are rejected in children treated prone. There was no difference in use or complications of general anesthesia, progression-free or overall survival, junctional recurrences, and radiation myelitis according to treatment position. Craniospinal irradiation in the supine position offers several advantages compared with treatment in the prone position, including patient comfort and ease of airway access. Klosky et al 9 conducted a prospective study evaluating medical, psychosocial, and demographic factors
related to pediatric distress during radiation therapy; the authors concluded that patients treated supine experienced significantly smaller changes in heart rate and behavioral distress compared with patients treated prone. In fact, treatment position (prone vs supine) was the only variable that reached statistical significance for these outcomes in their analysis. They attributed part of the increase in behavioral distress to the more limited field of vision during the procedure when patients are prone. In another study, 12 adult patients were positioned prone and supine for CSI. The supine position was considered more comfortable by patients based on a questionnaire. 6 Treatment in the prone position has implications on the physiology and potential complications associated with the use of anesthesia. Airway access can be difficult with the patient prone, and, although rare, there are reports of obstruction from secretions in the prone position. 10 The prone position is also associated with a decreased cardiac index, altered lung volume, and altered distribution of ventilation and pulmonary blood flow. 11 Finally, although rare, there are reports of direct and indirect pressure injuries to structures including the skin, trachea, and mediastinum, most commonly in patients with structural abnormalities predisposing them to complications. 12,13 The risk of these complications, although small, could be mitigated by treatment in the supine position. We did not have any anesthesia complication with either treatment position.
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Figure 2 Progression-free survival of patients with medulloblastoma treated with supine and prone craniospinal irradiation, P = .37.
Our results suggest that the supine position is also more reproducible with respect to the cranial fields than the prone position. In particular, there were fewer instances of correction for head tilt in patients treated supine. The main reason is better immobilization of the head in the supine position; in the prone position, the chin can tilt with the face mask. We are also able to use the 5-point mask in the supine position, which immobilizes the neck better. When treating the cranial fields in medulloblastoma, it is of critical importance to ensure adequate coverage of the cribriform plate and the inferior temporal lobes. The cribriform plate may inadvertently be partially spared by shielding intended to protect the eye due to its close proximity, and there are several studies describing recurrences in this region after inadequate coverage. 14,15 The most common reason for rejection of spine port films was to reposition the patient so that the spine is straight in the center of the treatment field. With the patient prone, the clinician and therapist can directly visualize the entry of the spinal beam and palpate the spine, ensuring that it is midline in the field. This is not possible with the supine patient, which may explain the higher number of rejected port films in our patients treated supine, with the difference being not statistically significant. Traditionally, craniospinal irradiation has been delivered with the patient prone because of the ability to easily visualize the entry of the beams. The calculation and measurement of a skin gap between spinal beams also offers added reassurance that there is no overlap in the divergence of the beams, which could put the patient at risk for radiation myelitis; or underdosage due to an inadvertently large gap, which could put the patient at risk for a junctional recurrence. In our study we found no cases of isolated junctional relapse or radiation myelitis. In addition, we found no difference in progression-free or overall survival between patients treated supine or prone. Our technique of utilizing daily intrafractional junction shifts means that if an inadvertent overlap occurred due to setup error, the overlap
Supine vs prane craniospinal irradiation
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would result in a lower fractional dose to the overlap region rather than a doubling of the dose that would occur if the junction was shifted between, rather than within, fractions. Because dose per fraction is an important factor in the development of late effects such as radiation myelopathy, we believe that using intrafractional junction shifts reduces the risk of this late complication. 16 Our results indicate that craniospinal irradiation can be performed safely in the supine position without compromising outcomes. There is an inherent bias in doing a retrospective comparison of patient positioning during CSI. The supine patients were treated in the more “modern era” of radiation therapy when there have been improvements in immobilization and imaging technology. Furthermore, therapists performing CSI setup become more experienced with time. For this reason, we compared the first half to the second half of patients treated with each technique to see if there was a difference in rejected port films. There was no difference in port film rejection rates over time in children treated prone or supine. To remove the possible bias introduced by different physicians checking port films, we (J.V. and A.C.P.) retrospectively reviewed each port film and gave a designation of accepted or rejected, which may not necessarily be the same as the original designation by the treating physician. Despite these limitations, we believe that this paper adds to the very limited literature regarding longterm survival outcome of patients treated in the supine position. To our knowledge, there has only been 1 report with long-term follow-up which shows that supine CSI has the same disease-free survival as prone CSI. 17 This paper also clinically validates previous methodologic reports of administering supine CSI. 5,8,18,19 In conclusion, our study shows that supine craniospinal irradiation in children with medulloblastoma does not compromise progression-free survival, or overall survival. Rejected port films in the cranium were more common with the prone position. There were no instances of radiation myelopathy in both the supine and prone CSI patients.
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Practical Radiation Oncology: Month 2014 13. Rittoo DB, Morris P. Tracheal occlusion in the prone position in an intubated patient with Duchenne muscular dystrophy. Anaesthesia. 1995;50:719-721. 14. Carrie C, Hoffstetter S, Gomez F, et al. Impact of targeting deviations on outcome in medulloblastoma: Study of the French Society of Pediatric Oncology (SFOP). Int J Radiat Oncol Biol Phys. 1999;45:435-439. 15. Jereb B, Krishnaswami S, Reid A, Allen JC. Radiation for medulloblastoma adjusted to prevent recurrence to the cribriform plate region. Cancer. 1984;54:602-604. 16. Schultheiss TE, Higgins EM, El-Mahdi AM. The latent period in clinical radiation myelopathy. Int J Radiat Oncol Biol Phys. 1984;10:1109-1115. 17. Slampa P, Pavelka Z, Dusek L, et al. Longterm treatment results of childhood medulloblastoma by craniospinal irradiation in supine position. Neoplasma. 2007;54:62-67. 18. Michalski JM, Klein EE, Gerber R. Method to plan, administer, and verify supine craniospinal irradiation. J Appl Clin Med Phys. 2002;3: 310-316. 19. Thomadsen B, Mehta M, Howard S, Das R. Craniospinal treatment with the patient supine. Med Dosim. 2003;28:35-38.