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Dose-escalated radiotherapy with simultaneous integrated boost for bone metastases in selected patients with assumed favourable prognosis

Vlatko Potkrajcic
Vlatko Potkrajcic
, 
Arndt-Christian Mueller
Arndt-Christian Mueller
, 
Bettina Frey
Bettina Frey
, 
Cihan Gani
Cihan Gani
, 
Daniel Zips
Daniel Zips
, 
Ruediger Hoffmann
Ruediger Hoffmann
, 
Sandra Frantz
Sandra Frantz
, 
Verena Warm
Verena Warm
, 
Frank Paulsen
Frank Paulsen
 y 
Franziska Eckert
Franziska Eckert
   | 13 dic 2022
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Article Category: Research Article
Publicado en línea: 13 dic 2022
Páginas: 515 - 524
Recibido: 26 jul 2022
Aceptado: 11 oct 2022
DOI: https://doi.org/10.2478/raon-2022-0053
© 2022 Vlatko Potkrajcic, Arndt-Christian Mueller, Bettina Frey, Cihan Gani, Daniel Zips, Ruediger Hoffmann, Sandra Frantz, Verena Warm, Frank Paulsen, Franziska Eckert, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Example of a radiation plan for a bone metastasis in the first lumbar vertebra. Gross tumour volume (GTV)40 was contoured by coregistered diagnostic positron emission tomography-computed tomography (PET-CT). Clinical target volume (CTV)30 included GTV40 and the whole vertebral body. Planning target volume (PTV)40 and PTV30 were generated with 2 and 5 mm margins (A). Panel (B) demonstrates isodose distribution. Dose-volume histograms (DVHs) PTV30, PTV40, CTV30 and GTV40 show dose coverage (C). GTV40 coverage is compromised due to spinal cord sparing (B, C). DVHs for both kidneys (purple and yellow), as well as spinal cord (red) are demonstrated as well (D). Medical history: patient was diagnosed with high-risk prostate cancer in 2012. Initial treatment included the combination of radiotherapy (prostate and pelvic lymph node) and long-term androgen-deprivation therapy. A single metastasis in the first lumbar vertebra was diagnosed in 2018. Radiotherapy with 30/40 Gy in 10 fractions with integrated simultaneous integrated boost (SIB) was applied for better local control. By the last documented follow up in 2021, no progression was observed in the irradiated metastasis. However, the patient developed diffuse skeletal metastases (treated with secondary androgen-deprivation therapy with abiraterone and enzalutamide).
Example of a radiation plan for a bone metastasis in the first lumbar vertebra. Gross tumour volume (GTV)40 was contoured by coregistered diagnostic positron emission tomography-computed tomography (PET-CT). Clinical target volume (CTV)30 included GTV40 and the whole vertebral body. Planning target volume (PTV)40 and PTV30 were generated with 2 and 5 mm margins (A). Panel (B) demonstrates isodose distribution. Dose-volume histograms (DVHs) PTV30, PTV40, CTV30 and GTV40 show dose coverage (C). GTV40 coverage is compromised due to spinal cord sparing (B, C). DVHs for both kidneys (purple and yellow), as well as spinal cord (red) are demonstrated as well (D). Medical history: patient was diagnosed with high-risk prostate cancer in 2012. Initial treatment included the combination of radiotherapy (prostate and pelvic lymph node) and long-term androgen-deprivation therapy. A single metastasis in the first lumbar vertebra was diagnosed in 2018. Radiotherapy with 30/40 Gy in 10 fractions with integrated simultaneous integrated boost (SIB) was applied for better local control. By the last documented follow up in 2021, no progression was observed in the irradiated metastasis. However, the patient developed diffuse skeletal metastases (treated with secondary androgen-deprivation therapy with abiraterone and enzalutamide).

Figure 2

Kaplan-Maier survival curves demonstrating local control (LC) and PFS. LC-rates at 1 and 2 years (calculated per total number of irradiated metastases) was 90.0 ± 6.7% and 83.3 ± 15.2%. Estimated PFS-rates at 1 and 2 years (calculated per number of patients) were 33.3 ± 11.6% and 22.2 ± 11.9%.
Kaplan-Maier survival curves demonstrating local control (LC) and PFS. LC-rates at 1 and 2 years (calculated per total number of irradiated metastases) was 90.0 ± 6.7% and 83.3 ± 15.2%. Estimated PFS-rates at 1 and 2 years (calculated per number of patients) were 33.3 ± 11.6% and 22.2 ± 11.9%.

Figure 3

Distribution of radiation therapy parameter. Target volume size for gross tumour volume (GTV)40, clinical target volume (CTV)30, planning target volume (PTV)40 and PTV30 is shown in panel (A). Mean values of the volume for GTV40, CTV30, PTV40 and PTV30 for the whole cohort were 25.90 cm3 (range 0.11-100.74 cm3), 140.04 cm3 (range 5.33-635.19 cm3), 40.43 cm3 (range 0.11-185.43 cm3) and 249.44 cm3 (range 22.28-1096.43 cm3). Panel (B) demonstrates target volume coverage for GTV40 minimal dose covering 98% of the target volume (D98), GTV40 maximal dose covering 2% of the target volume (D2), PTV40 D98, CTV30 D98 and PTV30 D98, as well as for GTV40 equivalent uniform dose (EUD). Mean value for D2 for GTV40 was 40.99 ± 0.65 Gy. Mean values for D98 for GTV40, CTV30, PTV40 and PTV30 were 37.26 ± 2.49 Gy, 30.94 ± 2.61 Gy, 35.75 ± 1.96 Gy and 29.10 ± 1.75 Gy. Mean value for GTV40 EUD was 38.21 ± 1.19 Gy. Panel (C) demonstrates radiation parameters for spinal cord (Dmax, D2 and D0.5cm). Mean values for spinal cord Dmax and D0.5ccm were 32.77 ± 1.18 Gy and 31.61 ± 2.07 Gy. Mean value for spinal cord D2 was 31.41 ± 2.36 Gy. Radiation parameter for kidneys (Dmean) are shown in panel (D). Mean value for Dmean for the kidneys was 4.18 ± 1.49 Gy. Maximal kidney Dmean value was 6.14 Gy. Panel e demonstrates moderate negative correlation of the size of the target volume with PTV30 D98 coverage, showing worse target volume coverage for larger target volumes.
Distribution of radiation therapy parameter. Target volume size for gross tumour volume (GTV)40, clinical target volume (CTV)30, planning target volume (PTV)40 and PTV30 is shown in panel (A). Mean values of the volume for GTV40, CTV30, PTV40 and PTV30 for the whole cohort were 25.90 cm3 (range 0.11-100.74 cm3), 140.04 cm3 (range 5.33-635.19 cm3), 40.43 cm3 (range 0.11-185.43 cm3) and 249.44 cm3 (range 22.28-1096.43 cm3). Panel (B) demonstrates target volume coverage for GTV40 minimal dose covering 98% of the target volume (D98), GTV40 maximal dose covering 2% of the target volume (D2), PTV40 D98, CTV30 D98 and PTV30 D98, as well as for GTV40 equivalent uniform dose (EUD). Mean value for D2 for GTV40 was 40.99 ± 0.65 Gy. Mean values for D98 for GTV40, CTV30, PTV40 and PTV30 were 37.26 ± 2.49 Gy, 30.94 ± 2.61 Gy, 35.75 ± 1.96 Gy and 29.10 ± 1.75 Gy. Mean value for GTV40 EUD was 38.21 ± 1.19 Gy. Panel (C) demonstrates radiation parameters for spinal cord (Dmax, D2 and D0.5cm). Mean values for spinal cord Dmax and D0.5ccm were 32.77 ± 1.18 Gy and 31.61 ± 2.07 Gy. Mean value for spinal cord D2 was 31.41 ± 2.36 Gy. Radiation parameter for kidneys (Dmean) are shown in panel (D). Mean value for Dmean for the kidneys was 4.18 ± 1.49 Gy. Maximal kidney Dmean value was 6.14 Gy. Panel e demonstrates moderate negative correlation of the size of the target volume with PTV30 D98 coverage, showing worse target volume coverage for larger target volumes.

Figure 4

Example of the radiation plan for a metastasis in femoral bone requiring subsequent surgery. The patient was diagnosed with bladder urothelial cancer in 2007. After tumour resection in 2007, the patient was diagnosed with diffuse bone metastases in 2018. Femoral bone metastasis was the only progressive tumour localization and higher-dose radiation therapy with 30/40 Gy with simultaneous integrated boost (SIB) was applied in 2018. Four months after the end of radiation therapy, the patient developed pain during axial loading of the knee due to a bone instability. Therefore, distal femur was replaced by a prothesis. Histopathological report after surgery showed a mixture of tumour and bone necrosis without signs of progressive vital tumour. No further local tumour progression in remaining femoral bone was documented in the follow up. Panel (A) demonstrates target volume delineation (gross tumour volume [GTV]40 = red, planning target volume (PTV)40 = dark blue, clinical target volume [CTV]30 = orange, PTV30 = light blue). Isodose distribution is shown in panel (B) (dark red = 40 Gy, red = 38.3 Gy, yellow = 34.9 Gy, light blue = 29.8 Gy, dark blue = 21.0 Gy). Panel (C) and (D) present magnetic resonance imaging (MRI) 4 months after the end of radiation therapy, showing tumour metastasis and necrosis. T1-weighted contrast-enhanced MRI (CE-T1WI) sequence (C) demonstrates a small contrast enhanced ring with large hypointense core. T2-weighted MRI (T2WI) sequence (D) shows diffuse bone oedema.
Example of the radiation plan for a metastasis in femoral bone requiring subsequent surgery. The patient was diagnosed with bladder urothelial cancer in 2007. After tumour resection in 2007, the patient was diagnosed with diffuse bone metastases in 2018. Femoral bone metastasis was the only progressive tumour localization and higher-dose radiation therapy with 30/40 Gy with simultaneous integrated boost (SIB) was applied in 2018. Four months after the end of radiation therapy, the patient developed pain during axial loading of the knee due to a bone instability. Therefore, distal femur was replaced by a prothesis. Histopathological report after surgery showed a mixture of tumour and bone necrosis without signs of progressive vital tumour. No further local tumour progression in remaining femoral bone was documented in the follow up. Panel (A) demonstrates target volume delineation (gross tumour volume [GTV]40 = red, planning target volume (PTV)40 = dark blue, clinical target volume [CTV]30 = orange, PTV30 = light blue). Isodose distribution is shown in panel (B) (dark red = 40 Gy, red = 38.3 Gy, yellow = 34.9 Gy, light blue = 29.8 Gy, dark blue = 21.0 Gy). Panel (C) and (D) present magnetic resonance imaging (MRI) 4 months after the end of radiation therapy, showing tumour metastasis and necrosis. T1-weighted contrast-enhanced MRI (CE-T1WI) sequence (C) demonstrates a small contrast enhanced ring with large hypointense core. T2-weighted MRI (T2WI) sequence (D) shows diffuse bone oedema.

Patient, tumour and therapy characteristics (number of patients n = 24, number of irradiated metastases n = 28), one patient with germ cell tumour not included

Age (Years)
Median and range 67.5 (28–81)
Sex (n = 24)
Female 7 29.2%
Male 17 70.8%
Histology (n = 24)
Prostate cancer 11 45.8%
Renal cell carcinoma 3 12.6%
Urothelial cancer 2 8.3%
Other* 8 33.3%
Localization of irradiated metastasis (n = 28)
Spine 20 71.4%
Rib 4 14.3%
Other (sternum, femur 2x, sacral bone) 4 14.3%
Oligometastatic vs. diffuse metastatic disease (n = 24)
Oligometastatic disease 16 66.7%
Diffuse metastatic disease 8 33.3%
Indication for radiation therapy (n = 24)
Oligometastatic disease 15 62.5%
Oligoprogression under systemic therapy 4 16.7%
Radiation resistant histology 3 12.5%
Intraspinal tumour component 2 8.3%
Systemic therapy (n = 24)
No systemic therapy 4 16.7%
Chemotherapy or immunotherapy 10 41.7%
Hormonal therapy 10 41.7%
eISSN:
1581-3207
Idioma:
Inglés
Calendario de la edición:
4 veces al año
Temas de la revista:
Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology, Radiology
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