craniospinal irradiation

CSI

1. TECHNIQUES OF CSI Dr. Abani Kanta Nanda 3 rd Year PG Student AHRCC Cuttack

2. Craniospinal irradiation (CSI) is a technique used in radiation therapy to deliver a prescribed amount of radiation to the entire cranial-spinal axis to achieve curative measures in the treatment of intracranial tumors . Craniospinal Irradiation – Treats anywhere CSF flows – Treatment fields typically include the brain to the thecal sac Definition

3. Series and parallel organ

4. Those who fail to read history are destined to suffer the repetition of its mistakes.

5. The concept of CSI was advanced by Dr Edith Paterson (wife of Ralston Paterson).  Before this the patients of Medulloblastomas were treated with posterior fossa or whole brain radiation History  She advocated the treatment of the entire neuraxis – bringing the concept of CSI  Paterson and Farr reported that with the use of cranio -spinal irradiation in 27 patient resulted in a 3 yr survival of 65% ( Acta Radiologica – 1953)

6. Medulloblastoma Pinealoblastoma Ependymoblastoma Intracranial Germ cell tumor ( germinoma ) Leukemia /lymphoma(with CNS axis mets ) Supratentorial PNET Cranio -spinal axis radiation therapy

7. Tumours prone for CSF Spread Tumours in proximity of CSF drainage pathways are prone for CSF spread

8.  Medulloblastoma forms the most common indication for CSI  In medulloblastoma , CSF Dissemination is known in 20 - 30 % of cases, producing a risk of metastases along the neuraxis .  Posterior fossa , spinal cord, ventricular walls & supratentorial region including the cribriform plate form the main sites of relapse  Being a radiosensitive tumour, RT is curative in upto 70 % of average risk patients Rationale

9.  Patient positioning and immobilization difficult, especially in paediatric cases (may require anaesthesia).  Large, irregular target volume.  Critical structures, with special importance to paediatric cases, who are potential long term survivors.  Problems of matching junctions between the divergent brain and spinal cord fields. WHAT MAKES CSI CHALLENGING

10. Proper immobilisation Dose homogeneity in the planning target volume Reducing the dose to organs at risk. WHAT SHOULD OUR AIM Evaluating the integral dose (ID) received by normal tissue. Reduce the planning time and waiting time for patients to start their radiotherapy course.

11. • Phase I : Craniospinal radiotherapy (two parallel opposed lateral cranial fields orthogonally matched with the posterior spinal field to cover the entire length of the spinal cord) • Phase II : Posterior fossa boost (whole posterior fossa irradiation or conformal boost to tumour bed) RADIOTHERAPY PLANNING

12. CSI (Phase I) 30 - 36 Gy in 18 - 21 fr over 4 weeks to the cranium @ 1.5- 1.8 Gy / fr ( 36 Gy in 20# over 4 weeks to the cranium @ 1.8 Gy per #) 30 - 36 Gy in 18 - 21 fr over 4 weeks to the spine @ 1.5 -1.8 Gy / fr ( 36 Gy in 20# over 4 weeks to the spine @ 1.8 Gy per #) Posterior fossa boost (Phase II) 18-20 Gy in 10-11 fr over 2 weeks to the posterior fossa ( 18 Gy in 10# over 2 weeks to the posterior fossa @ 1.8Gy/#) DOSE

13. The North American intergroup study (CCG-923/POG#8631)- The use of reduced-dose CSI (23.4 Gy ) alone (without chemotherapy) resulted in a significantly increased risk of isolated neuraxis failure and an event-free survival at 5 and 8 years of only 52%.(standard risk meduloblastoma ) CCG pilot study -reduced-dose CSI(23.4 Gy in combination with weekly vincristine ) followed by a boost to the posterior fossa to a total dose of 55.8 Gy , followed by adjuvant systemic chemotherapy consisting of vincristine 1.5 mg/m2, CCNU( Lomustin ) 75 mg/m2, and cisplatinum 75 mg/m2). Progression-free survival was 79% at 5 years. perez Other dosing schiduleds

14. CCG/POG phase III randomized study (A9961) the previous regimen was compared to a regimen in which the CCNU was replaced by cyclophosphamide . Event free survival at 4 years was approximately 85% in both arms. Such an approach is now considered to be the standard of care for children with standard-risk medulloblastoma in North America. perez

15. SFOP pilot study- tested HFRT to a CSI dose of 36 Gy without chemotherapy, early toxicity was reduced and progression-free survival at 3 years was 81%. (Perez) HIT-SIOP-PNET4 study- was to compare two radiotherapy protocols, Standard RT and HFRT. It was hypothesised that the HFRT regimen used would be superior for survival without causing more late effects. With a median follow up time of 7.8 years, the estimated OS at 10 years, remains not significantly different in the two treatment arms. (csi- 36 Gy /36#/48 days, 1 Gy BID, 8 hrs apart Tumor Boost: 32 Gy /32#/2.5 wks, 1 Gy BID, 6 hrs apart, 5 days/wk) (2016) Hyperfractionated radiotherapy (HFRT) in CSI

16. • Pituitary • Eyes / Lens • Cochlea / Inner ear • Parotid • Oral cavity • Mandible • Thyroid • Larynx Critical Normal Structures (OAR) • Heart • Lungs • Oesophagus • Liver • Kidneys • Gonads (Testes / Ovaries) • Breasts • Whole Pelvis( marrow)

17.  Detailed history & operative notes.  General physical & complete neurologic examination ( ophthalmoscopy included)  Gadolinium enhanced pre-op MRI of the brain & spine.  Immediate post-op MRI brain for residual disease status.  Post-op MRI of the spine (if pre-op scans not done).  CSF cytology Anesthetic evaluation before RT . PRE RT EVALUATION

18. Target Volume:-  Entire brain and its meningeal coverings with the CSF  Spinal cord and the leptomeninges with CSF  Posterior fossa – boost Energy:-  4-6 MV linac or Co60 Portals:-  Whole Brain: Two parallel opposed lateral field.  Spine: Direct Posterior field Scheduling of radiotherapy:-  Starting time : within 28 to 30 days following surgery ( perez )  Duration of treatment : 45 to 47 days

19. • Aimed at maximum tumor control with minimized normal tissue toxicity Positioning Immobilization Simulation Target and OAR Delineation Treatment Planning Junction shift Radiation Planning

20. Prone Position : Advantages : • Direct visualization of the field junctions. • Good alignment of the spine Disadvantages : • Uncomfortable, and larger scope for patient movement • Technically difficult to reproduce. • Difficult anesthetic maneuvers . Patient Positioning

21. Supine • More comfortable. • Better reproducibility • Safer for general anaesthesia BUT • Direct visualisation of spinal field is not possible Patient Positioning

22. 1.Orfit (Thermoplastic devices) for immobilization of the head, cervical spine & shoulder 2.Small children– inverted full body plaster cast with facial area open for access for anesthesia IMMOBILISATION

23. 3.Vaclock- is filled with styroform beads. When air is removed from the bag, it retains the shape and contour of the patient. 4.Alpha cradle- It uses two liquids, which when mixed together creat thermal reaction. When placed in a plastic bag and sealed, the chemical expands and conform to the patient’s body and then solidify.

24. 5.CSI board: Lucite( polymethyl methacrylate ) base plate fitted on which is a sliding semicircular lucite structure for head-rest & chin-rest. Slots from A to E to allow various degrees of extension.

25. Thermocol wedge for supporting the chest wall Alignment of the thoracic & lumbar spine parallel to the couch (to confirm under fluoroscopy)

26. Concern 1 Divergence of the upper border of the spinal field in case of single spinal field(and interdivergence of spinal fields in case of 2 spinal fields) Concern 2 Divergence of both cranial fields Critical issues in CSI fields

27.  Spinal field simulated first (get to know the divergence of the spinal field)  SSD technique  2 spinal fields if the length is > 36 cm  Upper border at low neck  Lower border at termination of thecal sac or S2 whichever is lower  In case of 2 spinal fields , junction at L2/L3 WHAT TO DO

28. Traditional recommendation for lower border of spinal field is inferior edge of S2 ( myelogram & autopsy studies). 8.7% patients have termination below S2-S3 interspace . MRI accurately determines the level of termination of the thecal sac & the extent of neuraxial disease if present. Termination of thecal sac Int J Radiat Oncol Biol Phys.  1998 Jun 1;41(3):621-4, scharf et.al.

29. 1. Cranio -spinal junction : various techniques; described subsequently 2. Spinal-spinal junction : no gap / fixed gap / calculated gap can be employed for matching as central axes of both the beams are parallel Field matching at both the junctions critical

30. Proponents of no gap argue that as medulloblastoma is radiosensitive tumor , small reduction in dose per fraction or total dose to part of Target Volume, owing to a gap, may produce significant difference in cell kill over a fractionated course of CSI, seen as local recurrences. Proponents of gap argue that no gap risks overdose at the junction & cervical spine & may result in disabling late toxicity Gap vs Nogap ?

31. Many institutes use a fixed gap ranging from <5 mm - 10 mm A customized gap calculated for each patient depending on field length & depth of prescription, is more appropriate Gap: Fixed or Calculated Gap calculation formula

32. CD BC DE AB = Khan’s physics 5 th ed pg-246

33. Spinal field- superior boarder at C3 – C4 junction such that field is not exiting through oral cavity. Conventional 2D planning Mark the divergent boundary of the superior margin of spinal field (red line) on lateral aspect of neck to provide a match line for the lateral cranial field(blue line). Open length of field to a maximum length and mark inferior border or

34. Width - vertebral body + 1 cm to include the intervertebral foramina; usual width 5 - 7 cm.

35. Lateral cranial fields Anterior posterior width includes entire skull with 2cm clearance. Superiorly, clearance to allow for symmetric field reduction while doing junction shift. Inferiorly, the border is matched with superior border of spinal field.

36. Most important is what not to shield Frontal ( cribriform plate) Temporal region In meduloblastoma nearly 15-20% of recurrences occur at cribriform plate site which is attributed to overzealous shielding, because of its proximity to ocular structure it often get shielded. Shielding

37. SFOP (French society Paediatric Oncology) Guideline- The recommended placement of block is 0.5cm below orbital roof 1cm below and 1cm in front of the lower most portion of the temporal fossa

38. How to match cranio spinal junction

39. Classically described technique. Divergence of spinal field into the cranial field is overcome with collimator rotation. Divergence of cranial field into spinal fields is overcome with couch rotation(rotated so that the foot end moves towards the gantry). Both rotations are performed during irrediation of the cranial fields. Collimator-Couch rotation

40. Half beam blocking

41. θ coll = Collimator angle to rotate (7-10 ) θ coch = Couch angle to ratate ( ~6 ) L 1 = the length of the posterior spinal field L 2 = the length of the lateral cranial field, (SSD is the SSD for the spinal field, and SAD is the source to axis distance for the cranial fields, assuming that the SSD technique is used for the spinal field and the SAD technique for the cranial fields)

42. 5mm overlap at 4mv photons 30 to 40% overdose (14Gy for 36Gy prescribed dose) which may exceed cord tolerance. ( Hopulka , 1993, IJROBP) Systematic error during radiotherapy delivery could further lead to an overlap or gap. Feathering after every 5 to 7 fraction smoothes out any overdose or underdose over a longer segment of cord Moving Junction in CSI

43. Usually shifted by 1 to 2 cm at each shift Done every few fractions( usually 5# to 7#). Either in cranially or caudal direction. Cranial inferior collimator is closed & spinal superior collimator is advanced by the same distance superiorly (if junction to be shifted cranially). Similarly, lower border of superior spinal field & superior border of inferior spinal field are also shifted superiorly, maintaining the calculated gap between them. Junction shift

44. Advantage Single spinal field and circumventing the issue of junction between two spinal fields Disadvantage Higher percentage depth dose and greater penumbra results in higher mean doses to all anterior normal structures,(mandible, esophagus , liver, lungs, heart, gonads and thyroid gland) Extended SSD technique

45. Borders Anterior: Posterior clinoid process. Posterior: Internal occipital protuberance. Inferior: C2-C3 interspace . Superior: Midpoint of foramen magnum & vertex or 1 cm above the tentorium (as seen on MRI). Posterior fossa boost Field arrangement Two lateral opposing fields.

46. Conventional Simulator films do not define: • Terminal location of the thecal sac. • Relationship between the optic globe and the cribriform plate. The cribriform plate may be located below or at the same level as the superior edge of the lens in 50% patients. Shielding the lens – underdosage of the cribriform plate. Nearly 25% of all recurrences occur in the supratentorial region. CT Simulation

47. • Virtual simulation of treatment fields without the patient. • Better definition of critical organs and target volume. • Graphical overlays of anatomic CT data onto digitally reconstructed radiographs (DRRs) and the viewing of all fields simultaneously in multiple CT-based planes improve field placement, matching, shielding accuracy & direct calculation of gap between the fields. CT Simulation-advantages

48. • Patient positioned using all ancillary devices and the spinal columns aligned with the sagittal external laser. • Three- fiducial reference marks placed on the mask in a transverse plane at the center of the head with the aid of the external laser. • Spiral CT images of 5 mm from the vault of skull – bottom of sacrum, with 3mm slices through the primary tumor /bed are acquired. • Target volumes and organs at risk are contoured on images. • Co-registered MRI and CT data sets are used for target volume delineation. Steps in CT simulation

49. CSI BY 3DCRT TECHNIQUE

50. Single isocentre for 2 lateral cranial fields and one upper spinal field.

51. . Field matching using field alignment option

52. IMRT plans provided better healthy tissue sparing than either the 2D or the 3D plans. IMRT results in better sparing of OARs without a significant increase in integral dose. CSI BY IMRT TECHNIQUE

53. CSI BY TIJJ(Three- Isocenter Jagged-Junction)

54. The plan used three field sets, each with a unique isocenter . One field set with seven fields treated the cranium. Two field sets treated the spine, each set using three fields. Fields from adjacent sets were overlapped, and the optimization process smoothly integrated the dose inside the overlapped junction. one IMRT plan is required for the entire target volume. The three isocenters were collinear, requiring only a longitudinal couch shift to move from one to the other, and were placed near the patient’s midline.

55. Sagittal view shows the dose distribution for one of the patient’s jagged-junction IMRT plan ( i ) and the conventional plan (ii) for the same patient. Regions A and B show the dose distribution in the cranial-spinal and superior-inferior junctions.

56. CSI BY TIOJ(Three- isocenter overlap-junction) TIOJ IMRT provides a simple and efficient choice for CSI treatment. It helps avoid typical CSI problems, such as over-long radiation fields and matching between the fields.

57. CSI BY VMAT A reduction of late sequelae and thus improved quality of life may be achieved by the use of VMAT. A VMAT planning solution for different lengths of craniospinal axis has been developed, with significant reductions in dose to the OAR around the brain, neck, and thoracic regions. HOWEVER there may be a risk of second malignancy due to increase of integral dose.

58. It is a rotational IMRT- no need for junction. Helical TomoTherapy delivers continuous arc–based intensity-modulated radiotherapy that gives high conformality and excellent dose homogeneity for the target volumes. Helical TomoTherapy allows for differential dosing of multiple targets, resulting in very good dose distributions. The use of pretreatment MVCT imaging with Helical Tomotherapy allows for increased precision with respect to patient positioning and use of a reduced PTV margin. CSI by Tomotherapy

59. Proton therapy- - Uniform dose distributuon to the posterior fossa and spinal cord with in the thecal sac. -Near complete organ sparing, lower probability of developing secondary hearing, hormonal defects. -Long term effect of neutron spill- not quantified.

60. Proton CSI is superior to other CSI modalities in terms of OAR doses and toxicities. There is a decreased risk of radiocarcinogenesis with proton CSI than with conventional radiation therapy. The reduction in risk of toxicity and radiocarcinogenesis offered by proton craniospinal irradiation appear to outweigh the increased costs.

61. Posterior spinal field

62. Lateral cranial field

63. Spinal field

64. Single isocentre for 2 lateral cranial fields and one upper spinal field.

65. • GTV- Tumor bed on MRI • CTV = GTV + 15 mm. • PTV = CTV + 3-5 mm, modified only at sella . • Immobilization accuracy +/- 3-5 mm. • 95% of isodose covers 100% of CTV & 95% Of PTV. • Constraints: • < 70% Supratentorial brain to receive > 50% boost dose. • < 80% Left & right cochlea to receive > 80% of boost dose. • < 50% Pituitary to receive > 30% of boost dose. • < 10% Left & right optic nerve & chiasma to receive > 50.4 Gy each. 3D CRT / IMRT Tumor Bed Boost

66. Acute Toxicity • Within first few weeks • Hair loss, skin reaction, sore throat, dysphagia , nausea and vomiting, fatigue • Bone marrow suppression • CNS toxicity – Acute radiation encephalopathy – Early cerebral necrosis Radiation Related Toxicity Late Toxicity • After four weeks • Bone marrow suppression • CNS toxicity – Delayed cerebral necrosis – Delayed cranial nerve damage – Delayed radiation myelopathy – Delayed motor-neuron syndrome

67. Craniospinal Irradiation – Treats anywhere CSF flows – Treatment fields typically include the brain to the thecal sac. Medulloblastoma forms the most common indication for CSI. There are ongoing trials for alternative dose of CSI to reduce toxicity- like reduced dosing schiduled with chemotherapy and HFRT. In standard risk meduloblastoma , dose can be reduced to 23.4Gy along with chemotherapy but in high risk meduloblastoma dose reduction is not recommended. Not to shield cribriform plate and Temporal region, as these are main site of recurrence due to overzealous shielding. Summary

68. Craniospinal and two spinal fields are matched using different methods otherwise there may be over dose to spine and devastrating result will occur. Feathering-Usually shifted by 1 to 2 cm at each shift, Done every 5# to 7#, Either in cranially or caudal direction. IMRT, VMAT, IGRT, Tomotherapy , Proton therapy are now more homogenous treatment plans, where target is receiving required dose and OARs are having less dose.

69. Thank you