Biophysical Analysis of Acute and Late Toxicity of Radiotherapy in Gastric Marginal Zone Lymphoma—Impact of Radiation Dose and Planning Target Volume

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Total body irradiation (TBI) is an essential part of various conditioning regimens prior to allogeneic stem cell transplantation, but is accompanied by relevant (long-term) toxicities. In the lungs, a complex mechanism induces initial inflammation (pneumonitis) followed by chronic fibrosis. The hereby presented analysis investigates the occurrence of pulmonary toxicity in a large patient collective and correlates it with data derived from normal tissue complication probability (NTCP) calculations. The clinical data of 335 hemato-oncological patients undergoing TBI were analyzed with a follow-up of 85 months. Overall, 24.8% of all patients displayed lung toxicities, predominantly pneumonia and pulmonary obstructions (13.4% and 6.0%, respectively). NTCP calculations estimated median risks to be 20.3%, 0.6% and 20.4% for overall pneumonitis (both radiological and clinical), symptomatic pneumonitis and lung fibrosis, respectively. These numbers are consistent with real-world data from the literature and further specify radiological and clinical apparent toxicity rates. Overall, the estimated risk for clinical apparent pneumonitis is very low, corresponding to the probability of non-infectious acute respiratory distress syndrome, although the underlying pathophysiology is not identical. Radiological pneumonitis and lung fibrosis are expected to be more common but require a more precise documentation by the transplantation team, radiologists and radiation oncologists.

Section: Introductionmentioning

confidence: 99%

Pulmonary Toxicity after Total Body Irradiation—An Underrated Complication? Estimation of Risk via Normal Tissue Complication Probability Calculations and Correlation with Clinical Data

Oertel

Kittel

Martel

et al. 2021

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“…Modern combined treatment for NHL consisted of personalized PET-guided therapy and improved the prognosis of this subset of patients, emphasizing the importance of acute and long-term toxicity [5]. Moreover, with advances in treatment planning techniques, including intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT), it is now possible to tailor radiation doses to individual patients, potentially reducing toxicity without compromising treatment efficacy [3,[6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…The evaluation of normal tissue toxicities is essential in assessing the safety and effectiveness of radiation therapy. Radiation-induced toxicity encompasses multiple acute and late side effects, such as radiation pneumonitis, cardiac toxicity, and esophagitis [6,[13][14][15][16][17][18][19][20]. The evaluation of normal tissue toxicities is essential in assessing the safety and effectiveness of radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have investigated the effects of field-size and dose prescription on different radiation-induced side effects. For example, Reinartz et al reported that reducing doses significantly impacted neighbouring organs in gastric lymphoma patients [6]. The use of biophysical dose-response relationships helped to predict adverse events for OAR, particularly for liver, spleen, and bowel toxicity, with corresponding normal tissue complication probability (NTCP) for elevated liver enzymes, low platelet count, and diarrhoea.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Modern Low Dose Involved Site Radiation Therapy on Normal Tissue Toxicity in Cervicothoracic Non-Hodgkin Lymphomas: A Biophysical Study

Roers,

Rolf,

Baehr

et al. 2023

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This biophysical study aimed to determine fitting parameters for the Lyman–Kutcher–Burman (LKB) dose–response model for normal tissue complication probability (NTCP) calculations of acute side effects and to investigate the impact of reduced radiation doses on the probability of their occurrence in supradiaphragmatic non-Hodgkin lymphoma (NHL) irradiation. A cohort of 114 patients with NHL in the cervicothoracic region, treated between 2015 and 2021 at the University Hospitals of Münster, Hamburg, and Essen, with involved site radiation therapy (ISRT), were included. Among them, 68 patients with aggressive NHL (a-NHL) received consolidative radiation therapy with 24–54 Gy following (R-)CHOP chemotherapy. Additionally, 46 patients with indolent NHL (i-NHL) underwent radiotherapy with 22.5–45.0 Gy. Two treatment plans were prospectively created for each patient (a-NHL: 30.0/40.0 Gy; i-NHL: 24.0/30.0 Gy). NTCP were then calculated using the optimized LKB model. The adapted dose–response models properly predicted the patient’s probability of developing acute side effects when receiving doses ≤ 50 Gy. In addition, it was shown that reduced radiation doses can influence the NTCP of acute side effects depending on the aggressiveness of NHL significantly. This study provided a foundation to prospectively assess the probability of adverse side effects among today’s reduced radiation doses in the treatment of NHL.

“…Today, the extensive RT fields of the past are no longer needed and the current internationally recommended treatment concept for the irradiation of gastric MZL lymphoma is an involved site radiotherapy (ISRT) with 24-30 Gy over 3 to 4 weeks [27,[34][35][36] (Figures 1 and 2; Table 1). Recent planning techniques attempt to further reduce the radiation dose in order to minimize the probability of normal tissue complication while maintaining tumor control [37]. (Burgers et al, 1988 [15]): the entire peritoneal cavity from the diaphragm to the pouch of Douglas and laterally to the side wall.…”

Section: Introductionmentioning

confidence: 99%

Development of Organ-Preserving Radiation Therapy in Gastric Marginal Zone Lymphoma

Rolf

Reinartz

Rehn

et al. 2022

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Gastric marginal zone lymphoma (gMZL) of mucosa-associated lymphoid tissue (MALT) may persist even after H. pylori eradication, or it can be primarily Helicobacter pylori (H. pylori) independent. For patients without the successful eradication of lymphoma, or with progressive disease, treatment options have historically included partial or total gastrectomy. Presently, in these instances, curative radiation therapy (RT) is the current standard of care. This review emphasizes the historically changing role of radiation therapy in gMZL, progressing from large-volume RT without surgery, to localized RT, on its own, as a curative organ-preserving treatment. This overview shows the substantial progress in radiation therapy during the recent two to three decades, from high-dose, large-field techniques to low-dose, localized target volumes based on advanced imaging, three-dimensional treatment planning, and advanced treatment delivery techniques. RT has evolved from very large extended field techniques (EF) with prophylactic treatment of the whole abdomen and the supradiaphragmatic lymph nodes, applying doses between 30 and 50 Gy, to involved-field RT (IF), to the current internationally recommended involved site radiation therapy (ISRT) with a radiation dose of 24–30 Gy in gMZL. Stage-adapted RT is a highly effective and safe treatment with excellent overall survival rates and very rare acute or late treatment-related toxicities, as shown not only in retrospective studies, but also in large prospective multicenter studies, such as those conducted by the German Study Group on Gastrointestinal Lymphoma (DSGL). Further de-escalation of the radiation treatments with low-dose 20 Gy, as well as ultra-low-dose 4 Gy radiation therapy, is under investigation within ongoing prospective clinical trials of the International Lymphoma Radiation Oncology Group (ILROG) and of the German Lymphoma Alliance (GLA).