Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients

Giantsoudi, D.; Seco, Joao; Eaton, Bree R.; Simeone, F. A.; Kooy, Hanne M.; Yock, Torunn I.; Tarbell, Nancy J.; DeLaney, Thomas F.; Adams, Judith; Paganetti, Harald; MacDonald, Shannon M.

doi:10.1016/j.ijrobp.2017.01.226

Cited by 34 publications

(24 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Superior sparing of bone marrow in the vertebral bodies, as well as even higher dose conformity can be achieved using proton irradiation 29,52. Favorable results regarding toxicity and tumor control have been described for proton CSI in pediatric tumors in several recent works, although proton therapy generally reintroduces the issue of field junctions 53–55…”

Section: Discussionmentioning

confidence: 99%

<p>Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis</p>

Shafie¹,

Böhm²,

Weber³

et al. 2019

CMAR

View full text Add to dashboard Cite

BackgroundLeptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10–15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC.Patients and methodsTwenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45–59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0–2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival.ResultsTwenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3–34.0, 95% CI: 11.0–32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein <100 mg/dL (P=0.018) and no more than mild or moderate neurologic deficits (NFS ≤2; P=0.007) were predictive of longer OS. So were the neurologic response to treatment (P=0.018) and the application of systemic therapy after RT completion (P=0.029). The presence of CSF flow obstruction was predictive of shorter OS (P=0.026). In multivariate analysis, age at LC diagnosis (P=0.018), KPI (P<0.001) and neurologic response (P=0.037) remained as independent prognostic factors for longer OS. Treatment-associated toxicity was manageable and mostly grades I and II according to the Common Terminology Criteria for Adverse Events v4.0. Eight patients (32%) developed grade III myelosuppression. Neurologic symptom stabilization could be achieved in 40.0% and a sizeable improvement in 28.0% of all patients.ConclusionCSI for the treatment of LC is feasible and may have therapeutic value in carefully selected patients, alleviating symptoms or delaying neurologic deterioration. OS after CSI was comparable to the rates described in current literature for patients with LC. The use of modern irradiation techniques such as helical IMRT is warranted to limit toxicity. Patient selection should take into account prognostic factors such as age, clinical performanc...

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis</p>

Shafie¹,

Böhm²,

Weber³

et al. 2019

CMAR

View full text Add to dashboard Cite

show abstract

“…A previous study of two pediatric CSI patients (8 and 11 years) reports average RBE values (using MCN (α/β)x 3Gy ) of 1.83 (heart), 1.58 (lungs) and 1.98 (thyroid) 16 . Using the same RBE model, our corresponding population median values for the heart (1.62) and lungs (1.27) were slightly lower.…”

Section: Discussionmentioning

confidence: 99%

“…For passively scattered (PS) proton CSI treatments, Giantsoudi et al 15 studied the LET and RBE with emphasis on RBE-weighted doses (RBE × dose) to the brainstem using two different variable RBE models, and reported mean RBE estimates consistently above 1.1 in the brainstem. Further, the RBE-weighted doses to OARs in two CSI patients were investigated in a study of vertebral column sparing techniques by applying five different treatment planning strategies 16 . This study showed elevated RBE for OARs distal to the spine, including the thyroid, lungs, esophagus and heart, and that the RBE values and doses were strongly dependent on the target volume delineation.…”

mentioning

confidence: 99%

Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons

Ytre-Hauge

Fjæra

Rørvik

et al. 2020

Sci Rep

View full text Add to dashboard Cite

cranio-spinal irradiation (cSi) using protons has dosimetric advantages compared to photons and isexpected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients. Variable RBE models were used to obtain RBE and RBE-weighted doses. RBE was quantified in terms of dose weighted organ-mean RBE (RBE d = mean RBE-weighted dose/mean physical dose) and effective RBE of the near maximum dose (D 2% ), i.e., where subscripts RBE and phys indicate that the D 2% is calculated based on an RBE model and the physical dose, respectively. compared to the median RBE d of the patient population, differences up to 15% were observed for the individual RBE d values found for the thyroid, while more modest variations were seen for the heart (6%), lungs (2%) and brainstem (<1%). Large inter-patient variation in RBE could be correlated to large spread in LET and dose for these organs at risk (OARs). For OARs with small inter-patient variations, the results show that applying a population based RBE in treatment planning may be a step forward compared to using RBE of 1.1. OARs with large inter-patient RBE variations should ideally be selected for patient-specific biological or RBE robustness analysis if the physical doses are close to known dose thresholds.Proton therapy has been established as an important radiation treatment modality for cancer, offering improved sparing of normal tissue compared to conventional radiation therapy with photons 1 . The dosimetric advantages of protons have already been shown for medulloblastoma patients receiving cranio-spinal irradiation (CSI) 2,3 , and early clinical outcomes suggest that similar disease control can be achieved with reduced toxicity compared to photon therapy 4-6 . Longer follow-up and more clinical data are awaited to draw firm conclusions on the clinical benefits of proton CSI 7 .Dosimetric benefits of proton CSI include a significant dose reduction to organs anterior to the spinal column, including the cochlea, transverse colon, stomach, kidney, heart, and lungs 8 . Besides the different spatial patterns in physical dose deposition, protons also have an increased biological effect compared to photons, i.e. protons produce more damage than photons from the same physical dose. This difference is currently accounted for by a dose scaling factor; the relative biological effectiveness (RBE). Although contemporary clinical proton treatment planning is based on a constant RBE of 1.1 (RBE 1.1 ), the proton RBE is known to vary with linear energy transfer (LET), tissue type and physical dose 9-11 . In particular, the RBE increases due to the increase in LET towards the end of the proton beam range. The need to investigate the RBE further and to and to provide clinical solutions accounting for variations in the RBE has therefore recently bee...

show abstract

“…63 Vertebral body sparing craniospinal irradiation using proton therapy is also being explored as a method to reduce bone marrow toxicity, allow increased tolerance to chemotherapy, and reduce radiation-induced growth toxicity. 64,65 Vertebral body sparing intensity modulated proton therapy may spare a significant portion of the vertebral body from radiation doses that would cause growth impairment (10-20 Gy). 64 In a report of long-term follow-up of 5 pediatric patients with medulloblastoma treated with vertebral body sparing proton therapy, 2 patients were clinically diagnosed with scoliosis and treated conservatively.…”

Section: Reduced Final Heightmentioning

confidence: 99%

“…64,65 Vertebral body sparing intensity modulated proton therapy may spare a significant portion of the vertebral body from radiation doses that would cause growth impairment (10-20 Gy). 64 In a report of long-term follow-up of 5 pediatric patients with medulloblastoma treated with vertebral body sparing proton therapy, 2 patients were clinically diagnosed with scoliosis and treated conservatively. 65 No patients reported chronic back pain, required spine surgery, or were noted to have thoracic lordosis; however, diminished growth of the posterior portions of the vertebral bodies was identified with an average posterior-to-anterior height ratio of 0.88.…”

Section: Reduced Final Heightmentioning

confidence: 99%

A Road Map for Important Centers of Growth in the Pediatric Skeleton to Consider During Radiation Therapy and Associated Clinical Correlates of Radiation-Induced Growth Toxicity

Rao

Ladra

Dunn

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

With the increasing use of advanced radiation techniques such as intensity modulated radiation therapy, stereotactic radiation therapy, and proton therapy, radiation oncologists now have the tools to mitigate radiation-associated toxicities. This is of utmost importance in the treatment of a pediatric patient. To best use these advanced techniques to mitigate radiation-induced growth abnormalities, the radiation oncologist should be equipped with a nuanced understanding of the anatomy of centers of growth. This article aims to enable the radiation oncologist to better understand, predict, and minimize radiation-mediated toxicities on growth. We review the process of bone development and radiationinduced growth abnormalities and provide an atlas for contouring important growth plates to guide radiation treatment planning. A more detailed recognition of important centers of growth may improve future treatment outcomes in children receiving radiation therapy.

show abstract

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients

Cited by 34 publications

References 27 publications

<p>Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis</p>

<p>Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis</p>

Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons

A Road Map for Important Centers of Growth in the Pediatric Skeleton to Consider During Radiation Therapy and Associated Clinical Correlates of Radiation-Induced Growth Toxicity

Contact Info

Product

Resources

About