Reirradiation for Sinonasal Adenoid Cystic Carcinoma in a Low-Middle Income Setting: A Case Report and Literature Review

Abstract

Introduction

Reirradiation for recurrent adenoid cystic carcinoma (ACC) of the head and neck poses significant clinical challenges, particularly in low- and middle-income countries where access to advanced radiation modalities such as proton or carbon ion therapy is limited. Given the tumor’s radioresistant nature and the risk of cumulative toxicity to critical structures, reporting experiences with accessible and precise photon-based techniques remains essential. This case highlights the potential of volumetric-modulated arc therapy (VMAT) as a feasible reirradiation option in such settings.

Case Presentation

We report the case of a 79-year-old male with a history of left ethmoidal sinus ACC initially treated with surgery followed by cobalt-based radiotherapy. Eighteen years later, the patient presented with an inoperable local recurrence. A multidisciplinary tumor board recommended reirradiation using VMAT. A total dose of 60 Gy in 30 fractions was delivered, with careful dosimetric planning to respect cumulative tolerance thresholds of organs at risk (OAR). The treatment was well-tolerated, with no acute grade ≥3 toxicities. Post-treatment imaging showed a marked reduction in tumor volume, and the patient had no severe late toxicity during follow-up or distant metastasis.

Conclusions

This case illustrates the potential role of VMAT as a viable reirradiation strategy for head and neck ACC, particularly in resource-limited settings. It emphasizes the importance of individualized treatment planning, accurate dose delivery, and multidisciplinary evaluation in achieving tumor control while minimizing toxicity. Such experiences contribute valuable insights into the management of complex recurrent tumors, where therapeutic options are limited.

Introduction

Adenoid cystic carcinoma (ACC) is a rare yet aggressive malignancy constituting around 1–2% of all head and neck cancers [1, 2]. Deceivingly indolent, it has a relentless disease course due to its characteristic perineural invasion, giving it a high propensity for locoregional recurrence and distant metastasis [1, 2]. The mainstay of treatment typically comprises surgical resection followed by adjuvant radiotherapy. Nevertheless, local recurrences remain a significant clinical challenge, necessitating the exploration of salvage therapies, including reirradiation (reRT).

reRT in the context of head and neck malignancies is fraught with challenges, primarily due to concerns regarding cumulative radiation toxicity. However, advancements in radiotherapy, either with photons including intensity-modulated radiotherapy and volumetric-modulated arc therapy (VMAT) or with particles such as proton therapy (PT) or carbon ion radiotherapy (CIRT), have facilitated precise tumor targeting while improving OAR sparing, thereby rendering reRT a more feasible option in selected patients.

This report presents a case of recurrent sinonasal ACC managed with VMAT-based reRT. We discuss the rationale for treatment decisions, key dosimetric considerations, and the broader implications for optimizing reRT strategies in similar clinical scenarios. The completed CARE [3] Checklist for this case report is included as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000547432).

Case Presentation

A 79-year-old fit male was initially diagnosed in 2006 with ACC of the left ethmoidal sinus. Primary management involved extensive surgical resection and enucleation of the left eye with negative margins, followed by adjuvant radiotherapy to a total dose of 64 Gy in 32 fractions, delivered via 2D-cobalt therapy.

In 2007, the patient experienced local recurrence, prompting a second surgical resection without additional radiation. Over the next 7 years, he remained free of disease, until another recurrence necessitated further surgical intervention.

Eighteen years after the initial diagnosis, the patient presented with a slowly enlarging left facial mass which he initially neglected. Magnetic resonance imaging (MRI) found a tumoral mass centered on the resection cavity, with intermediate T1 and T2 signals and hyperintense signals on diffusion-weighted imaging, measuring 30 × 54 × 58 mm, invading the remaining posterior ethmoidal cells, the left retro maxillary zygomatic space with lysis of the frontal process, the infra temporal fossa with infiltration of the proximal insertion of the lateral pterygoid muscle, and it is responsible for lysis of the left alveolar process and hard palate with bulging in the oral cavity. We also noted the presence of a necrotic left jugal subcutaneous adenomegaly, measuring 21 × 24 × 36 mm. Biopsy confirmed the same tumoral nature of an ACC. No distant metastases were shown on the computed tomography (CT) of the head, chest, abdomen, and pelvis, classifying the disease as rT4N1M0. Given the inoperable nature of the recurrence, the multidisciplinary tumor board advocated for definitive reRT.

Treatment and Dosimetric Planning

The patient was immobilized with a thermoplastic head-mask. Simulation CT scans with 3-mm slice thickness were used for treatment planning on the Eclipse system (Varian Medical System Inc., version 16). Delineation of the gross tumor volume was assisted by image registration with contrast enhanced T1-weighted MRI. A margin of 5 mm was set for the clinical target volume and 3 mm for the planning target volume (PTV). Cranial nerves V, VII, IX, and X were partially included due to proximity of recurrence. To estimate the previous dose absorbed by OAR at the first course of radiation in 2007, we put in place the beams according to the original 2D-cobalt treatment plan and measured the dose delivered at the OAR. We applied a 50% discount to the delivered doses to each OAR. Dosimetric planning was meticulously tailored thereafter to minimize OAR exposure, achieving the constraints detailed in Table 1. reRT was planned using VMAT with two partial arcs. A total dose of 60 Gy (2 Gy per fraction) was prescribed as the PTV (Fig. 1). Treatment was delivered on a Varian iX Linac using image-guided radiotherapy with daily cone-beam CT.

Table 1.

Summary of organ at risk constraints and delivered dose at reRT

​	​	Estimated dose delivered at first radiation, Gy	Cumulative dose constraint, Gy	New constraint for reRT after dose discount, Gy	Dose at reRT, Gy
Brainstem	Dmax	38.8	60	40.6	20.4
Spinal cord	Dmax	14.8	50	42.6	16.2
Right optic nerve	Dmax	38	54	35	27.8
Chiasma	Dmax	57.7	54	25.15	24.7
Right carotid	Dmax	35	120	82.5	35.27
Left carotid	Dmax	71.4	120	64.3	49.5
Right eye	Dmax	23	50	38.5	26
Mandibula	Dmax	54	100–120	60–80	60.8
Right lens	Dmax	23.5	6–15	3.5	7.6
Left temporal lobe	Dmax	67.7	70–72	36.15–38.15	49.9

D_max, near-point maximum dose.

Fig. 1.

Axial, sagittal, and coronal cross sections highlighting the PTV in blue. Dose in color-wash showing isodose 95% achieving good conformality with the PTV (V95% = 98%).

Follow-Up Imaging and Outcome

The patient was followed up weekly during radiotherapy to assess tolerability and manage acute side effects. During treatment, he developed grade 2 radiodermatitis and grade 2 radiomucositis as per the Common Terminology Criteria for Adverse Events (CTCAE V.5), both of which were managed with symptomatic local treatment. A MRI conducted 6 weeks post-treatment demonstrated partial tumor regression, with a residual lesion measuring 18 × 46 × 52 mm and a minimal increase in size of the left jugal subcutaneous adenomegaly measuring 22 × 33 × 36 mm, with notably an absence of otherwise suspicious cervical adenomegaly.

Follow-up at 9 months revealed further regression, with the primary lesion measuring 13 × 37 × 28 mm and regression in size of the left jugal subcutaneous mass measuring at 19 × 9 mm. The patient remains under surveillance, with no evidence of distant metastatic progression. Representative MRI images of the patient before and 9 months after reRT, illustrating tumor response and radiation-induced changes, are shown in Figure 2.

Fig. 2.

Axial, sagittal, and coronal MRI views showing the tumor lesion with an intermediate T1 signal and heterogeneous enhancement. a Before reRT. b Nine months after reRT showing tumor regression.

Discussion

reRT of head and neck malignancies entails a delicate balance between oncological benefit and toxicity risk. Our decision for this current case was guided by prognostic factors suggesting improved outcomes in patients with an interval of ≥36 months since prior radiation, absence of previous concurrent chemotherapy, and a cumulative reRT dose of ≥60 Gy. These criteria were established in a retrospective study that included only squamous cell carcinomas of the head and neck [4]. However, given the absence of specific reRT criteria for ACCs, we extrapolated from these findings to inform our approach.

In the reRT setting, consensus on temporally based dose recovery is not universally established, and the supporting evidence varies across different organs, except for the central nervous system, for which there is sufficient evidence from preclinical models and retrospective series in humans [5]. However, given the substantial 18-year gap between irradiation courses in this case, we deemed it appropriate to apply a 50% dose reduction to the maximum absorbed dose by OARs [6].

Being aware of the risk of carotid artery blow-out, radionecrosis, or radiomyelitis, we set cumulative dose constraints based on published dosimetric guidelines, such as those in Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC), or other peer-reviewed publications. For example, it was paramount to keep the cumulative dose to the carotid artery below 120 Gy [7] and to the mandible below 100 Gy [8].

Particle therapy has demonstrated impressive outcomes in head and neck ACC. A study on PT for skull base ACC reported a 5-year local control rate of 93%, and a 5-year disease-free and overall survival (OS) rates of 56% and 77%, respectively [9]. Another study demonstrated 5-year local control rates of 80% and locoregional control rates of 78% in patients with sinonasal cancers treated with PT [10]. Similarly, a multicenter study of CIRT for head and neck ACC reported an estimated 5-year local control and OS rates of 68% and 74%, respectively [11].

Photon therapy for head and neck cancers is known to be just as efficient as particle therapy in terms of target coverage, dose homogeneity inside the PTV, and OAR sparing [12]. Particle therapy does, however, allow for a better dose conformity for the PTV and better sparing of most organs at risk at medium-to-low doses, which can be particularly useful in the reRT setting [12].

Table 2 summarizes retrospective studies on reRT for ACC of the head and neck published in the past decade. Most studies utilized either PT or CIRT. Reported progression-free survival (PFS) and OS outcomes were variable but generally indicated the efficacy of high-dose reRT in achieving local control [13–18]. In a retrospective study that included 229 patients with recurrent head and neck cancers, Held et al. [15] reported a median local PFS after reRT with CIRT of 24.2 months and a median OS of 26.1 months. Notably, patients who had ACC had a significantly better local PFS compared with patients with other tumor entities (hazard ratio 0.488; 95% CI, 0.297–0.802; p =0.005) and had a better median OS of 33.6 months.

Table 2.

Summary of retrospective studies involving reRT of ACC of the head and neck

Study	Population	Median age	Tumor histology	Radiation technique	Concurrent systemic therapy	Median interval from first radiation	Median prescribed dose at reRT, GyE	Median cumulative dose at reRT	Median follow-up	PFS	OS
Jensen et al. [13], 2015	47	54	ACC	92% CIRT	No	61 months	51	128 Gy BED	14 months	47.4% at 2 years	63.3% at 2 years
				8% IMRT+CIRT
Hayashi et al. [14], 2019	48	56.5	43.8% melanoma	CIRT	No	24.2 months	54	136.3 Gy (RBE)	27.1 months	29.4% at 2 years	59.6% at 2 years
			35.4% ACC
			12.5% sarcomas
			8.3% other
Held et al. [15], 2019	229	–	54.1% ACC	CIRT	No	3.9 years	51	132.8 Gy	28.5 months	24.2 months	26.1 months
			26.2% SCC
			8.3% ADK
			11.4% other
Vischioni et al. [16], 2020	51	60	74.5% ACC	CIRT	No	6.33 years	60	–	19 months	52.2% at 2 years	64% at 2 years
			11.8% mucoepidermoid carcinoma
			5.8% myoepithelial carcinoma
			7.9% other
Nangia et al. [17], 2022	6 (3 in a reRT setting)	51.5	ACC	PT or PT+IMRT	Yes	5 years	70	–	–	–	–
Mahé et al. [18], 2023	10	–	ACC	3 IMRT	No	53.5 months	​	–	26 months	55.60%	41% at 2 years
				7 PT

ACC, adenoid cystic carcinoma; SCC, squamous cell carcinoma; PT, proton therapy; CIRT, carbon ion radiotherapy; BED, biological equivalent dose; reRT, reirradiation; PFS, progression-free survival; OS, overall survival; IMRT, intensity-modulated radiotherapy.

Nevertheless, financial and infrastructural constraints limit accessibility to PT or CIRT. To date, besides China, India, and Saudi Arabia, no other low- or middle-income country has an operational particle therapy center [19]. Consequently, VMAT remains an attractive alternative that enables high-dose reRT while maintaining a favorable therapeutic ratio [20]. In our case, although the clinical outcome at 9 months post-reRT is encouraging, this follow-up period remains relatively short to draw definitive conclusions regarding long-term disease control and late toxicities. Continued surveillance is planned to better assess the durability of response and potential late effects.

Conclusion

This case underscores the viability of VMAT-based reRT for recurrent head and neck ACC. Through meticulous patient selection, individualized dosimetric optimization, and interdisciplinary collaboration, reRT can provide meaningful disease control while minimizing toxicity. Future research should focus on refining dose constraints, integrating emerging radiotherapy technologies, and further elucidating the long-term outcomes of reRT in this challenging oncologic setting.

Statement of Ethics

Ethical approval is not required for case reports in accordance with local and national guidelines. Written informed consent was obtained from the patient for their anonymized information to be published in this article.

Conflict of Interest Statement

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this article.

Funding Sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

Conceptualization: Wael Kaabia and Alia Mousli. Data curation: Wael Kaabia, Najla Attia, and Bouchra Naija. Writing of the original draft: Wael Kaabia and Najla Attia. Writing – review and editing: Alia Mousli. Supervision and validation: Asma Ghorbel, Khadija Ben Zid, Semia Zarraa, Rim Abidi, and Chiraz Nasr.

Funding Statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data Availability Statement

All data analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.