Reirradiation: Standards, challenges, and patient-focused strategies across tumor types

Abstract

Reirradiation (reRT), defined as administering a course of radiation therapy to a specific area previously irradiated, is an evolving treatment strategy for locoregionally recurrent cancer that offers significant potential and poses inherent challenges. Advances in such techniques as intensity-modulated and stereotactic body radiation therapy have improved precision, making reRT a viable option for complex scenarios previously deemed high-risk. Nevertheless, reRT remains associated with substantial risks-including life-threatening side effects, functional impairments, and psychosocial effects-which must be carefully balanced against the patient's overall health and the likelihood of achieving cancer control or palliation. Patient selection is essential to optimize outcomes while mitigating risks. Decisions should account for tumor characteristics at the time of primary diagnosis and recurrence, elapsed time since prior treatment, the possibility of delivering meaningful doses to the tumor, and the cumulative irradiation tolerance of normal tissues. Advanced imaging modalities, such as functional magnetic resonance imaging and fluorine-18-labeled fluorodeoxyglucose-positron emission tomography, are important for distinguishing recurrences from treatment-induced changes, refining treatment targets, and minimizing exposure to healthy tissue. Combined treatment with systemic regimens-targeted therapies and immunotherapy in particular-offers promising opportunities but requires coordination to manage side effects. Standardized guidelines, such as those from the European Society of Therapeutic Radiology and Oncology-European Society for Research and Treatment of Cancer, are essential for improving the consistency of reporting, guiding clinical decision making, and fostering patient-centered care. Multidisciplinary collaboration and ongoing research, particularly through clinical trials, are central to fully exploiting reRT strategies. In addition, the development of innovative techniques, such as proton therapy, would likely enable safer treatments. These efforts aim to improve the therapeutic balance of reRT, enhancing outcomes and quality of life.

Keywords: advanced imaging techniques; decision‐making; locoregional recurrence; radiation oncology; reirradiation.

FIGURE 1

Classification of reRT scenarios and related concepts. Red indicates the current target volume (tumor to treat in reRT), and green represents the previously treated volume (previously irradiated area). reRT indicates reirradiation. Figure created by Jonas Willmann using Biorender.com.

FIGURE 2

Comprehensive multidisciplinary evaluation for patient reRT. EBRT indicates external‐beam radiation therapy; reRT, reirradiation. Figure created by Jonas Willmann using Biorender.com.

FIGURE 3

Multiparametric pelvic MRI illustrates a local recurrence 8 months after the completion of chemoradiotherapy and a watch‐and‐wait strategy in a patient with rectal cancer. (A) An axial T2‐weighted MRI shows subtle tissue irregularity in the anterolateral anal canal and lower rectovaginal septum, but the lesion remains poorly conspicuous. (B) A diffusion‐weighted image highlights a focal area of markedly restricted diffusion (green arrow), confirming the presence of a 3‐cm recurrence. Diffusion‐weighted imaging was instrumental in detecting the lesion in this anatomically complex, previously irradiated area. MRI indicates magnetic resonance imaging.

FIGURE 4

Tumor recurrence versus brain radionecrosis in a patient aged 75 years who was previously irradiated for a right ethmoid adenocarcinoma. (A) Gadolinium‐enhanced T1‐weighted MRI revealed a right frontal tissue mass, (B,C) which was confirmed as tumor recurrence by hypercaptation on ¹⁸F‐DOPA PET imaging. Subtotal resection confirmed the recurrence, and the patient underwent reRT to the residual tumor. ¹⁸F‐DOPA indicates fluorine‐18–labeled dihydroxyphenylalanine; MRI, magnetic resonance imaging; PET, positron emission tomography; reRT, reirradiation.

FIGURE 5

Morphologic challenges in head and neck cancer reRT. Challenges for image registration are highlighted between the initial RT and the reRT planning CT scans because of significant changes in patient morphology. The top row (sagittal views) shows a first patient with (A) an initial laryngeal tumor, (B) a new oral cavity tumor 9 years after RT, with a markedly stooped posture, and (C) the corresponding registration between both scans, illustrating the difficulties encountered. The bottom row (axial views) shows a second patient with (D) an initial parotid tumor, (E) a recurrence in the same location 6 years later, with postsurgical changes, including a reconstructed mandible with a metal insert (orange), and (F) the resulting registration used for reRT planning, which was particularly challenging. CT indicates computed tomography; reRT, reirradiation; RT, radiation therapy.

FIGURE 6

Steps for dose summation in reRT treatment planning. (A) Image registration, starting with rigid alignment of the initial (CT1) and reRT (CT2) data sets, followed by deformable registration, with vectors linking corresponding locations. (B) Dose mapping, projecting the initial dose distribution onto the reRT CT (CT2). (C) Plan summation in EQD2Gy, accounting for fraction‐size effects and any DSE, such as tissue recovery, to estimate the cumulative dose. CT indicates computed tomography; DSE, dose‐scaling factor; EQD2Gy equivalent dose in 2‐gray fractions; reRT, reirradiation.

FIGURE 7

Dosimetric comparison between 3D‐CRT and IMRT for spinal reRT. (A) The first‐course plan (20 Gy in five fractions) delivered using IMRT. (B,C) Second‐course reRT plans (15 Gy in three fractions) simulated using (B) 3D‐CRT and (C) IMRT. (D,E) Cumulative EQD2Gy distributions resulting from the summation of first‐course and second‐course plans for (D) 3D‐CRT (E) and IMRT, respectively. The dose color wash is standardized across all panels: orange indicates ≥95% of the prescribed dose; yellow, ≥90%; turquoise, ≥80%; royal blue, ≥70%; purple, ≥55%; and dark blue, ≥50%. The spinal cord is contoured in green. Compared with 3D‐CRT, IMRT achieves a steeper dose gradient and superior sparing of the spinal cord. The cumulative maximum dose to the spinal cord (0.03 cm³) reaches 58 Gy EQD2Gy with the IMRT‐based reRT plan, whereas it exceeds 69 Gy EQD2Gy using the 3D‐CRT approach. 3D‐CRT indicates three‐dimensional conformal radiation therapy; EQD2Gy equivalent dose in 2‐gray fractions; Gy, grays; IMRT, intensity‐modulated radiation therapy; reRT, reirradiation; RT, radiation therapy.

FIGURE 8

Dosimetric comparison between IMRT and SBRT for lung reRT. Comparison between (A) a simulated IMRT plan delivering 50 Gy in 25 fractions and (B) the clinical SBRT plan delivering 50 Gy in five fractions in a previously irradiated patient with a peripheral lung recurrence. The IMRT plan represents a conventional, homogeneously distributed approach. In contrast, the SBRT plan shows a steeper dose fall‐off and higher intratumoral dose (up to 107% of the prescription). The high‐dose volume (orange area, ≥95%) is also smaller with SBRT, because no clinical target volume margin beyond the gross tumor volume was applied. These features illustrate how SBRT may improve the therapeutic ratio in selected reRT scenarios by combining reduced irradiated volume and increased dose conformality. Gy indicates grays; IMRT, intensity‐modulated radiation therapy; reRT, reirradiation; SBRT, stereotactic body radiation therapy.

FIGURE 9

Brachytherapy for central pelvic recurrence after prior radiation therapy. CT scan images in (A) axial and (B) coronal views showing the treatment of a central pelvic recurrence using high‐dose‐rate brachytherapy in a patient who had already received pelvic RT. The patient, previously treated with surgery and chemoradiation for cervical cancer, developed a local recurrence in the vaginal vault 18 months later. A special applicator was used to place radioactive sources directly into the tumor area. The colored lines represent different dose levels, showing how the radiation is tightly focused on the tumor while sparing nearby healthy tissues. This example illustrates how brachytherapy can safely deliver a second course of RT in selected patients. CT indicates computed tomography; RT, radiation therapy.

FIGURE 10

Comparison of proton therapy and IMRT for reRT of a patient with recurrent nasopharyngeal cancer. Dose distributions for (A) proton therapy and (B) IMRT are compared. Warmer colors represent higher doses, and cooler colors represent lower doses. In A, proton therapy exhibits superior sparing of critical structures, particularly the brain (teal), brainstem (orange), and parotids (green). Gy indicates grays; IMRT, intensity‐modulated radiation therapy; reRT, reirradiation.

FIGURE 11

ReRT plan for a patient with recurrent glioblastoma. (A) Initial CT scan and treatment plan for the first irradiation. (B) Gadolinium‐enhanced T1 MRI revealing an in‐field recurrence 8 months after the initial RT, with a color wash representing the stereotactic RT reRT plan. The reRT volume and technique were carefully optimized to minimize the dose to healthy brain tissue. CT indicates computed tomography; MRI, magnetic resonance imaging; reRT, reirradiation; RT, radiation therapy.

FIGURE 12

Differentiating radiation‐induced fibrosis from local recurrence in a patient aged 62 years who was previously irradiated for right upper lobe pulmonary adenocarcinoma. (A) Serial CT scans showed progressive opacifications, which were indeterminate for fibrosis or recurrence. (B) ¹⁸F‐FDG PET imaging confirmed the recurrence. (C) SBRT plan with PET‐guided targeting to ensure precise reRT while sparing fibrotic lung tissue. ¹⁸F‐FDG indicates fluorine‐18–labeled fluorodeoxyglucose; CT, computed tomography; PET, positron emission tomography; reRT, reirradiation; SBRT, stereotactic body radiation therapy.

FIGURE 13

Multiparametric MRI for SBRT reRT planning in a patient with recurrent prostate cancer. A patient aged 70 years with a history of prostate cancer who was previously treated with RT and hormone therapy presented with a PSA rise to 2.07 ng/mL. Multiparametric MRI identified a 14‐mm recurrent lesion, which was confirmed as invasive adenocarcinoma (Gleason score 8) by biopsy. (A) CT simulation scan with the patient's GTV outlined in red. (B) Multiparametric MRI in the treatment position, enhancing precise GTV delineation for SBRT. CT indicates computed tomography; GTV, gross tumor volume; MRI, magnetic resonance imaging; PSA, prostate‐specific antigen; RT, radiation therapy; SBRT, stereotactic body radiation therapy.

FIGURE 14

Partial breast irradiation in the context of reRT. This is a treatment‐planning CT scan for partial breast irradiation in the setting of reRT for breast cancer. The magenta contour outlines the breast; surgical clips, marked in yellow, aid in identifying the primary tumor bed location. The primary tumor bed, shown in red, represents the original recurrence site. The CTV, generated as 2 cm minus the tumor‐free margin around the primary tumor bed, is displayed in light blue, covering the reRT area while sparing surrounding healthy tissue. CT indicates computed tomography; CTV, clinical target volume; reRT, reirradiation.