Russian Medical Review
ISSN 2311-7729 (Print), 2619-1571 (Online)

Russian Medical Review

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Потенциальные преимущества протонной терапии у пациентов с саркомой сердца

Background 

Primary cardiac tumors are very rare tumors with a prevalence of 0.2%. More than 80% of cardiac tumors are benign while the proportion of sarcomas is less than 2% [1]. These tumors have a very limited array of treatment options available due to their localization. The efficacy of chemo- and radiotherapy is poor as well. Nonetheless, radiotherapy may be considered first-line treatment in local recurrences after prior surgery and pharmacotherapy [2-7]. Unfortunately, even modern 3D conformal intensity-modulated radiotherapy does not always deliver the prescribed radiation dose to the target without exceeding tolerance dosages for healthy tissues. When performing cardiac radiotherapy, it is of crucial importance to minimize the exposure of healthy myocardium, lungs, esophagus, and spinal cord.

In recent years, a method of proton beam therapy is extensively developed worldwide. In contrast to other types of irradiation, proton beam depth dose distribution is characterized by a slow increase with an increasing penetration depth (plateau) followed by dose maximum (Bragg peak). The amplitude of Bragg peak is 3-4 times higher than surface dose. Currently, proton beam therapy is the most powerful tool to provide high dose conformity. As a result, proton beam therapy helps significantly reduce radiation exposure to healthy tissues as compared with photon beam therapy [8].

This paper describes two case reports of cardiac sarcoma patients who received proton therapy and compares two radiation treatment plans using proton or photon beam therapy.  

Proton therapy planning was performed using EclipseTM treatment planning system (Varian, Palo Alto, CA, USA). Radiotherapy was performed using ProBeam® proton therapy system (Varian, Palo Alto, CA, USA) with pencil beam scanning.

EclipseTM treatment planning system was also used for photon therapy planning. Dose distribution was achieved using intensity-modulated radiation therapy (IMRT) technique or volumetric modulated arc therapy (VMAT) technique.

Case report 1 

In July 2017, a 55-year-old woman who experienced angina pectoris was referred to a cardiologist. Pulmonary valve stenosis and right ventricle (RV) tumor were diagnosed. In August 2017, tricuspid valve repair and pulmonary valve cusp replacement with an autologous pericardial graft were performed. Pleomorphic sarcoma was diagnosed by histology. No chemotherapy was performed postoperatively, observation was recommended. In October 2017 and March 2018, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) was performed, no abnormal tracer uptake was detected.

In September 2018, PET-CT revealed a metabolically active lesion in the RV cavity sized 20 × 17 × 15 mm by scintigraphy (standardized uptake value/SUVmax 11.09). In addition, enhanced glucose metabolism was detected in the anterior mediastinal, upper paratracheal, and paraesophageal lymph nodes.

The patient was referred to cardiac surgeons. However, the surgery could not be carried out due to technical challenges. Considering a predictable poor response to chemotherapy, it was decided to perform proton beam therapy.

Pre-treatment cardiac contrast-enhanced magnetic resonance imaging (MRI) revealed an endophytic infiltrative tumor mass sized 43 × 28 × 43 mm in the basal segment of the RV that spreads into the cavity and to the tricuspid and pulmonary valves causing tricuspid stenosis.

The total radiation dose delivered to the primary tumor and affected lymph nodes was 66 Gy and 60 Gy, respectively, while the single fraction equivalent dose (SFED) was 2.2 Gy and 2 Gy, respectively.

During the 8-month follow-up, no adverse effects of the radiotherapy were reported. MRI performed after 1, 3, and 8 months demonstrated a progressive decrease in the sizes of the RV infiltrative tumor mass to 36 × 16 × 39 mm (see Fig. 1).

Рис. 1. Результаты МРТ пациентки А. до лечения (А – аксиальная проекция, В – сагиттальная проекция) и спустя 8 мес. после протонной терапии (C – аксиальная проекция, D – сагиттальная проекция) Fig. 1. MRI of woman A. before the treatment (A – axial view,

Photon beam treatment planning was performed using IMRT technique to compare radiation exposure in photon and proton beam therapy. The mean doses to the right and left lung, the mean and maximum dose to the spinal cord, the volume of the lung receiving 5 Gy and 20 Gy, and the volume of the heart receiving 40 Gy were significantly lower in proton beam therapy. Radiation exposures when using various radiotherapy techniques are listed in Table 1.

Таблица 1. Показатели лучевой нагрузки при использовании протонного и фотонного облучения, рассчитанные для пациентки А. Table 1. Radiation doses in proton beam and photon beam therapy calculated for woman A.

Case report 2 

A 15-year-old boy was diagnosed with pericardial Ewing’s sarcoma. In 2016, the boy underwent surgical treatment followed by chemotherapy. In 2018, the second round of chemotherapy was performed that induced tumor stabilization. However, 3 months after the treatment, a continued pericardial tumor growth was revealed.

Considering the continued pericardial tumor growth even after chemotherapy, it was decided to perform proton beam therapy.

Pre-treatment MRI revealed a tumor mass in the basal and mid segments of the anterior wall of the left ventricle (LV) sized 64 × 62 × 59 mm. The tumor spreads along the posterior wall of the aortic root and the inferior wall of the pulmonary trunk and is adjacent to the anterior wall of the left inferior pulmonary vein.

The total radiation dose delivered to the primary tumor and SFED was 55.8 Gy and 1.8 Gy, respectively.

During the 8-month follow-up, no adverse effects of the radiotherapy were reported. MRI performed after 1, 4, and 8 months demonstrated a progressive decrease in the sizes of the LV infiltrative tumor mass to 47 × 24 × 33 mm (see Fig. 2). No reduction in myocardial contractility or ejection fraction was detected by echocardiography.

Рис. 2. Результаты МРТ пациента Т. до лечения (А – аксиальная проекция, В – сагиттальная проекция) и спустя 8 мес. после протонной терапии (C – аксиальная проекция, D – сагиттальная проекция) Fig. 2. MRI of man T. before the treatment (A – axial view, B –

Photon beam treatment planning was performed to compare radiation exposure in photon and proton beam therapy. Considering the volume and the location of the target, optimal radiotherapy dose distribution was achieved when using VMAT technique. V5, V10, the mean dose to the left lung, heart V40, the mean dose to the right lung, and the dose to the spinal cord were significantly lower in proton beam therapy. Radiation exposures when using various radiotherapy techniques are listed in Table 2.

Таблица 2. Показатели лучевой нагрузки при использовании протонного и фотонного облучения, рассчитанные для пациента Т. Table 2. Radiation doses in proton beam and photon beam therapy calculated for man T.

Discussion 

The clinical experience with proton beam therapy is currently gained worldwide. Novel prospective studies on the role of protons in the treatment for oncological disorders are initiated every year. The comparison of treatment plannings with the measurement of the quality of radiation dose delivery to the target organ and radiation exposure to healthy tissues is one of the methods to assess the safety and potential efficacy of proton beam therapy.

In case report 1, photon beam treatment planning was performed using IMRT technique. Considering a complex target shape and a need for lymph node irradiation, optimal radiotherapy dose distribution was achieved when using 7 static fields. Proton beam treatment planning was performed using 5 fields (see Fig. 3). According to both treatment plans, 95% of the planning target (i.e., myocardial tumor) volume were covered by 98% of the prescribed dose. However, photon beam therapy failed to cover the affected lymph nodes (i.e., only 80% of the planning target were covered by 98% of the prescribed dose). Meanwhile, 94% of the lymph nodes were covered by 98% of the prescribed proton beam therapy dose.

Рис. 3. Пациентка А.: план фотонного облучения с использованием методики IMRT и 7 статичных полей (А) и план протонного облучения с применением 5 полей (В) Fig. 3. Woman A.: photon beam radiation treatment schedule using IMRT and 7 static field (A) and pr

Proton beam therapy reduced the mean dose to the esophagus by 30% and the volume of the esophagus receiving 50 Gy by 15%. In addition, a significant decrease in the radiation exposure to the right lung was also achieved.

In case report 2, photon beam treatment planning was performed usingVMAT technique. As a result, the coverage of the target was close to a perfect one, i.e., 98% of the tumor were covered by 98% of the prescribed dose. Proton beam treatment planning was performed using only 2 fields that provided similar target coverage (see Fig. 4).

Рис. 4. Пациент Т.: план фотонного облучения с использованием методики VMAT (А) и план протонного облучения с применением 2 полей (В) Fig. 4. Man Т.: photon beam radiation treatment schedule using VMAT (A) and proton beam radiation treatment schedule usin

VMAT technique provides excellent tumor coverage by the prescribed dose and allow for the reduction of radiation exposure to the heart, esophagus, and left lung. However, the dose to the right lung increases. Meanwhile, the major advantage of proton beam therapy for this patient is a minimal radiation exposure to the parenchyma of the right lung (a 15-fold reduction in the mean dose) and spinal cord (a 5-fold reduction in the maximum dose) compared to photon beam therapy (see Fig. 5-7). This contributes to a significantly lower risk of pneumonitis, esophagitis, and radiation myelitis.

Рис. 5. Гистограмма «доза – объем», характеризующая лучевую нагрузку на правое (квадраты) и левое (треугольники) легкое у пациента Т. Синий цвет – кривые для фотонного облучения, зеленый цвет – кривые для протонного облучения Fig. 5. Histogram “dose-volum

Рис. 6. Пациент Т. Гистограмма «доза – объем», характеризующая лучевую нагрузку на спинной мозг. Синий цвет – фотонное облучение, зеленый цвет – протонное облучение Fig. 6. Histogram “dose-volume” characterizes radiation exposure to spinal cord in man T.

Рис. 7. Пациент Т.: распределение дозы при использовании методик протонного (А) и фотонного (В) облучения Fig. 7. Dose distributions in photon beam therapy (A) and proton beam therapy (B)

Conclusions  

In patients with cardiac sarcoma, adjuvant radiotherapy improves the local control over the disease. In general, these patients have microscopic tumor foci within the resection margin. Patients with macroscopic tumor foci require high-dose radiotherapy (60 Gy or more) that is significantly higher than the tolerated dose for the heart. Proton beam therapy for cardiac sarcomas significantly reduces radiation exposure to healthy tissues in the simultaneous delivery of high doses to the tumor thus providing the local control over the disease. Further studies are required to determine the patients in whom proton beam therapy will be of crucial importance to improve the control over the disease, overall survival, and the quality of life.


About the authors:

Nikolay A. Vorobyov — Cand. of Sci. (Med.), Head of the Department of Proton Beam Therapy, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation; St. Petersburg State University, 7/9, Universitetskaya emb., St. Petersburg, 199034, Russian Federation; I.I. Mechnikov North-Western State Medical University, 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; ORCID iD 0000-0002-6998-5771.

Nataliya I. Martynova — radiologist of the Department of Proton Beam Therapy, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation, ORCID iD 0000-0002-1679-5173.

Dmitriy V. Bondarchuk — radiologist of the Department of Radiodiagnostics, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation, ORCID iD 0000-0001-8752-0591.

Denis A. Antipin — radiologist of the Department of Proton Beam Therapy, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation, ORCID iD 0000-0002-4198-3870.

Anton V. Kubasov — medical physicist, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation, ORCID iD 0000-0001-7672-6703.

Alexey V. Mikhailov — Cand. of Sci. (Med.), Head of the Department of Radiation Therapy, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation; St. Petersburg State University, 7/9, Universitetskaya emb., St. Petersburg, 199034, Russian Federation; I.I. Mechnikov North-Western State Medical University, 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; ORCID iD 0000-0002-5240-7203.

Andrey I. Lyubinskiy — medical physicist, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation, ORCID iD 0000-0002-5694-8701.

Georgiy I. Andreev — Head of the Division of Medical Physics, Berezin Sergey Medical Institute. 2 build. 3, Esenin str., St. Petersburg, 194354, Russian Federation, ORCID iD 0000-0001-7590-5187. 

Contact information: Nikolay A. Vorob’ev, e-mail: vorobyov@ldc.ru. Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 20.02.2020, revised 02.03.2020, accepted 09.03.2020.



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