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Background: Surgical resection with adjuvant concurrent radiochemotherapy is the standard of care for stage III–IV oral cavity cancer. In some cases, the dynamic course of the disease is out of the prepared schedule of treatment. In that event, a stereotactic radiosurgery boost might be the only chance for disease control. Case presentation: Here, we present a case study of a patient with oral cancer who underwent surgery. During adjuvant radiotherapy, a metastatic cervical lymph node was diagnosed based on fine ‑needle aspiration biopsy. To increase the total dose to the metastatic tumor, a stereotactic radiosurgery boost of 1 × 18 Gy was performed two days after the last fraction of conventional radiotherapy. The early and late tolerance of this treatment were posi‑ tive. During the 18‑month follow‑up, locoregional recurrence was not detected. The patient died due to secondary malignancy. Conclusions: This paper shows that a stereotactic radiosurgery boost added to adjuvant conventional radiotherapy is an effective approach permitting the maintenance of good local control in well‑selected patients. Keywords: Squamous cell carcinoma, Stereotactic radiotherapy, Radiosurgery boost, Head and neck cancer Introduction Reoperation is one of the options for proceeding, but the Squamous cell carcinoma is the most common malig- constricted healing process caused by radiation-induced nant tumor in the head and neck anatomical region. The acute side effects limits the possibility of its safe execu - lip and oral cavity are the predominant sites of head and tion. Another option is the attempted use of an uncon- neck carcinoma according to the Globocan database in ventional scheme of treatment, such as increasing the terms of morbidity and mortality . A surgical proce- total dose of radiation. In this paper, we describe how the dure involving tumorectomy and lymphadenectomy, fol- application of a high-dose boost can avoid a reoperation lowed by radiotherapy (RTH) or radiochemotherapy, is procedure and achieve a complete response and good the standard of treatment [2, 3]. Unfortunately, in some local control (LC). cases, disease progression occurs in a short period of time after the operation during adjuvant treatment. Case report We present a 43-year-old nonsmoking and nondrink- ing white male with oral cancer on the left side of the tongue. A biopsy sample taken from the tumor revealed a *Correspondence: Natalia.Amrogowicz@io.gliwice.pl G2 keratinizing squamous cell carcinoma. On a CT scan 1St Radiation and Clinical Oncology Department, Maria Sklodowska‑ Curie performed two months before the operation, the radiolo- National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland Full list of author information is available at the end of the article gist described a primary tumor measuring 15 × 10 mm © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Polanowski et al. Radiation Oncology (2022) 17:103 Page 2 of 6 with peripheral contrast enhancement and two sus- pected, probably metastatic lymph nodes on the left side of the neck in groups III and IV, size 17 × 14 mm and 26 × 16 mm, respectively. Distant metastases were ruled out on chest X-ray and abdominal ultrasound. Moreo- ver, anamnesis proved previous lower extremity deep vein thrombosis, but Doppler ultrasound ruled out active disease. The surgical procedure included excision of the left half of the tongue, the floor of the mouth and the sidewall of the throat and bilateral cervical lymph node dissec- tion in groups I-V on the left side and I-III on the right side. The second part of the operation involved recon - struction by using an anterolateral thigh flap. After three Fig. 1 Conventional radiotherapy. Dose distribution shown on the days, reoperation was performed due to hemorrhage CT scan. Isocenter plane of the 3rd stage of initial plan from the wound after lymphadenectomy. The final his - topathology report revealed G2 keratinizing squamous cell carcinoma, stage IVa (pT3 pN2b, AJCC 8th edition). next stage, confirming metastasis of the squamous cell Additional risk factors included perineural invasion of carcinoma. The multidisciplinary case conference urged small nerves, an unfavorable pattern of invasion with the application of a single-fraction stereotactic radiosur- small islands (the worst pattern of invasion, 4), a closest gery (SRS) boost of 18 Gy to the metastatic lymph node. margin below 1 mm, and five metastatic lymph nodes (of After 29 days of conventional treatment, a new 5-point 49 lymph nodes dissected) without extracapsular exten- mask, a new CT scan without contrast and an MR scan sion at levels II, IV, V on the left side. The novel prog - with gadolinium intravenous contrast (both with 1 mm nostic histopathological grading system in oral squamous slice thickness) in the supine position were performed cell carcinoma based on tumor budding revealed G-2 . in the planned stereotactic boost process. The GTV There were 102 budding foci detected per 10 high-power boost volume was 0.7 cm . A 3 mm margin was added to the fields. Two to four cell-sized nests or single-cell invasion GTV to create a PTV volume of 3.1cm . A new was observed. A multidisciplinary case conference quali- boost boost treatment plan consisting of four arcs was prepared. Four fied the patient for postoperative radiochemotherapy, 6 MV FFF (flattening filter-free) photon beams with a but he refused systemic treatment. Given the patient’s maximal dose rate of 1400 MU/min were utilized. The decision, radiotherapy alone was recommended. Five- dose that fully covers target volume was selected as the point head, neck and shoulder masks were employed for prescribed isodose level, so that the minimum dose in patient immobilization, and a CT scan (3 mm slice thick- the target volume was 100% of the prescribed dose and ness) without intravenous contrast with the patient in the the maximum dose was 108.4%. The angle range of arcs supine position was performed in the planning radiother- was adapted to the boost localization and was limited apy process. The dose prescription involved the bilateral to the right and front sides of the patient. The boost was lymph nodes I-V to a total dose of 50 Gy in 25 fractions, delivered two days after the last fraction of conventional the left side neck in groups II-V to a total dose of 60 Gy in radiotherapy with the same linear accelerator. Overall 30 fractions and the tumor bed with bilateral submandib- treatment time totaled 50 days. Figures 2 and 3 show ular lymph nodes to a total dose of 66 Gy in 33 fractions the dose distribution of the SRS boost and the sum of (Fig. 1). The VMAT (volumetric modulated arc therapy) conventional RTH with SRS boost, respectively. Dose technique was applied. In the first stage of treatment, analysis of the conventional and stereotactic radiother- three full arcs were used, followed by three arcs lateral- apy is presented consecutively in Tables 1 and 2. During ized to the left side of the neck in the second stage. In the radiotherapy, oral mucositis and moist desquamation third stage, two frontal arcs were applied. Radiotherapy (grade 3, CTCAE v5.0) were observed in the irradiated was performed by linear accelerators (Clinac 23EX; Var- area, which subsided within three months of follow up. ian Medical Systems, Palo Alto, CA, USA) with an energy Additionally, Staphylococcus aureus and Klebsiella oxy- of 6 MV and maximal dose rate of 600 MU/min. Two toca were identified from the throat culture in six week weeks after the beginning of radiotherapy, ultrasound of conventional treatment, subsequently treated using of the neck was performed due to a suspected lump in antibiotic therapy consistent with the antibiogram (clin- group III on the right side. It revealed a 16 × 9 mm lymph damycin, amoxicillin/clavulanate potassium). Blood tests node. Fine-needle aspiration biopsy was performed in the P olanowski et al. Radiation Oncology (2022) 17:103 Page 3 of 6 Table 1 Conventional radiotherapy: dose analysis in target volumes and organs at risk Minimal Mean dose (Gy) Maximal dose (Gy) dose (Gy) CTV 47.51 62.76 70.41 PTV 25.40 61.20 70.41 CTV 58.05 65.54 70.41 PTV 54.90 64.73 70.41 CTV 63.68 67.22 70.41 PTV 60.25 66.92 70.41 Lens right 1.81 2.04 2.22 Lens left 1.93 2.17 2.517 Eye right 1.54 2.12 2.81 Fig. 2 Stereotactic radiosurgery boost. Dose distribution shown on Eye left 1.70 2.25 3.035 the CT scan. Isocenter plane of the stereotactic boost plan Cochlea right 2.84 5.47 10.64 Cochlea left 2.82 6.32 12.17 Chiasm 2.17 2.38 2.56 Optic nerve right 2.18 2.36 2.58 Optic nerve left 2.21 2.39 2.58 Brainstem 1.99 6.82 26.84 Brain 1.00 4.02 35.51 Mandible 3.90 46.55 66.14 Parotid gland right 3.22 32.72 65.03 Parotid gland left 5.67 32.75 65.65 Spinal canal 2.07 33.32 44.46 Larynx 45.53 53.41 67.44 Thyroid gland 26.84 51.91 61.66 Table 2 Stereotactic radiosurgery boost: dose analysis in target volumes and most important organs at risk (in other organs the maximal dose did not exceed 0.5 Gy) Minimal dose Mean dose (Gy) Maximal Fig. 3 Dose distribution in the Eclipse system (physical dose sum (Gy) dose (Gy) of the conventional radiotherapy and the stereotactic radiosurgery boost). Isocenter plane of the stereotactic boost plan GTV 18.23 19.11 19.51 boost PTV 18.00 18.88 19.52 boost Spinal canal 0.02 0.31 2.18 showed grade 1 anemia and leukopenia after 24 and 33 Larynx 0.06 1.47 7.44 fraction respectively, and normalized seven months after Thyroid gland 0.03 0.44 9.91 treatment. Three, ten and thirteen months after the end Blood vessels 0.27 11.08 19.24 of radiotherapy, CT scans and laryngological examina- tions did not prove locoregional recurrence. Chest X-ray and abdominal ultrasound did not detect any metastatic examination after endoscopic ultrasound-guided fine changes one year after treatment. Xerostomia G2 was needle aspiration (EUS-FNA) proved squamous cell car- the only symptom of late toxicity fifteen months after cinoma with moderate PD-L1 membrane expression radiotherapy. (< 50%). Acknowledgment of the tumor in the chest as At 17 months of follow-up, the patient reported cough- lung cancer or metastatic disease due to oral cancer was ing, suffocation and bloody sputum. difficult; nevertheless, a further aggressive course might A CT scan revealed infiltration (64 × 65 × 100 mm) suggest a new primary cancer. The patient was qualified in the 3rd segment of the right lung, encompassing the for palliative radiotherapy to a total dose of 30 Gy in 10 hilum and central part of the mediastinum. Pathological fractions (VMAT technique, single arc, gantry angle Polanowski et al. Radiation Oncology (2022) 17:103 Page 4 of 6 30.0–210.0 deg) for the tumor in the chest (systemic and demonstrated favorable OS in class II patients, who treatment was contraindicated in terms of performance underwent treatment with IMRT. There were no differ - status—ECOG 2). Three months later, multiple metas - ences in OS in class III regardless of applying IMRT or tases in the mediastinum, right lung, spleen and bones SBRT technique. Acute toxicity in grade ≥ 3 was about were detected by PET/CT. The most painful osteolitic 5 percentages points higher in IMRT than SBRT. Late lesion in the left ischium and femoral head was irradiated toxicity was similar in both groups . Compared with in one fraction to 8 Gy (two-dimensional radiotherapy salvage treatment, our case report provides an exam- technique, two coaxial opposite beams from AP and PA ple of the utilization of SBRT in primary radiotherapy directions were used). The patient died the next month. as a method of escalation of the total dose during con- ventional radiotherapy in RPA class I patient. Dutch Discussion researchers described an SBRT boost (3 × 5.5 Gy) deliv- The diagnosis of head and neck cancer is associated with ered with a CyberKnife for 195 patients with T1-T3 oro- unfavorable prognosis, especially in IV stage. Median pharyngeal squamous cell carcinoma after 46 Gy IMRT survival time is particularly poor for oral cavity cancer (23 daily fractions, six fractions per week). Concurrent (23 months) compared to other localizations in head and systemic treatment (cisplatin or cetuximab) was admin- neck (e.g. 59 months for laryngeal cancer). Most com- istered only in 6% of patients (stage T3 or N2c without mon pattern of failure is locoregional recurrence con- contraindications for systemic treatment). The 2-year cerning even 50% of patients. Rapid regional recurrence OS and DFS were 87% and 81%, respectively. Sixty-five can be associated with tumor size, extranodal extension patients required a feeding tube due to acute toxicity, and and perineural invasion [5–7]. Stage of disease and his- 47 patients developed grade ≥ 3 late toxicity. This paper topathological risk factors fall into the pattern of aggres- confirms that a combination of SBRT and IMRT can lead sive course and poor prognosis of our patient, effectively to successful outcomes, but side effects were the most treated with using of high-dose stereotactic radiotherapy serious problem of this treatment. Most soft tissue necro- boost without locoregional relapse. Stereotactic body sis appears during the 12 months after the completion radiotherapy (SBRT) in the head and neck region is of RTH . In the same follow-up period, we did not increasing in popularity, especially in recurrent cases. detect any serious side effects associated with the SBRT Roh reported 36 patients (44 sites) who were reirradi- boost. Our patient reported xerostomia G2, which was ated due to locally recurrent head and neck cancer to a bound with an exceeded tolerance dose in the parotid total dose of 18–40 Gy in 3–5 fractions with CyberKnife glands during conventional treatment as a result of need- radiosurgery as salvage treatment. Eleven sites concerned ing to deliver a prescribed dose to the oral cavity. Inter- lymph nodes (neck and retropharyngeal). Thirty-one esting results were presented by Sher et al. on a group of 44 sites were evaluated for response. The author sug - of 29 patients with Tis to T2 glottic cancer who were gested that stereotactic body radiotherapy could be an treated with hypofractionated radiotherapy—4 patients effective treatment for recurrent disease with relatively to 50 Gy in 15 daily fractions, 13 patients to 45 Gy in good tolerance (thirteen patients with acute complica- 10 fractions (three fraction per week) and 12 patients to tions, three patients with late complications including 42.5 Gy in 5 twice-weekly fractions. During a median necrosis) . Moreover, a meta-analysis including ten follow-up of 39.2 months, 5 local failures (4 patients articles (575 patients) explored problems of reirradia- with primary T2 tumors and 1 patient with primary T1b tion using SBRT in management of recurrent or second tumors) were diagnosed: two in the 50 Gy/15 fractions primary head and neck cancer not suitable for salvage group and three in the 45 Gy/10 fractions group. There surgery. Total doses ranged from 24 to 44 Gy (median, were no local recurrences in the 42.5 Gy/5 fractions 30 Gy) realized in 3–6 fractions (median, 5 fractions). group. The authors also highlighted dose-limiting tox - The pooled rate of 2-year OS and LC were 30.0% and icity grade 3 dysphagia and grade 4 laryngeal edema in 47.3%, respectively. Complete response rate got 31.3% one patient who was treated to 42.5 Gy/5 fractions and of patients. In researchers’ view, severe toxicity rate one patient who was treated to 45 Gy/10 fractions. They (grade ≥ 3) was acceptable, below 10% . Collected data suggested that the large target volumes (PTVs, 17 cm by Vargo et al. from eight institutions in USA showed and 21.3 c m ) and active smoking were the causes of the that using IMRT technique (≥ 40 Gy) for definitive reir - elevated risk of radiation-induced toxicity . Regard- radiation of unresectable, recurrent or second primary ing our case report, the patient did not smoke, and the head and neck cancer gave 35.4% 2-year OS rate in PTV volume was slightly greater than 3 c m ; thus, this comparison to 16.3% for SBRT (1–5 fractions of ≥ 5 Gy/ could be the reason why the SBRT boost was well toler- fraction). In this paper, researchers took into account ated. The localization of the target volume should not Recursive Partitioning Analysis (RPA) classification be ignored; treatment of nodal metastases seems safer P olanowski et al. Radiation Oncology (2022) 17:103 Page 5 of 6 Author contributions than that of a primary tumor of the mucosa or digestive PP—conception, realization of the treatment, writing the manuscript. AP, DK‑B, or respiratory tract. Data from the literature indicate NA, KP—the literature researching, writing the manuscript. AG—preparing that using very high single fraction radiation doses (15– of the radiation therapy plan. EC—the histopathological examination and immunohistochemical analysis. KS—the final revision. All authors read and 25 Gy) in a mouse model could generate strong CD8 + T approved the final manuscript. cell-dependent immunity, leading to tumor reduction . Due to the patient’s declining systemic therapy dur- Funding Not applicable. ing radiotherapy, the stereotactic single fraction boost may have contributed to compensating for the lack of Availability of data and materials chemotherapy by stimulating the immune system. Curi- The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. ous results were obtained from a Czech study involving patients ineligible for surgical treatment with advanced- Declarations stage floor of the mouth cancer . After radical radio - therapy to a total dose of 70–72.5 Gy in 35/50 fractions, Ethical approval and consent to participate a 10 Gy boost in two fractions was applied. The 5-year The patient had possibility to ask questions and he gained answers for all issues. The consent on radiotherapy treatment was obtained from patient. follow-up revealed 62% local control and 27% overall survival (secondary malignancy was the cause of death Consent for publication in 5% of cases) with good tolerance—acute mucositis All authors read and approved the final manuscript. G3 and dysphagia G3 in 10% of patients. In the context Competing interests of our case report and previously published experience The authors declare that they have no competing interests. , involving adenoid cystic carcinoma of the choa- Author details nae and nasopharynx successfully treated with an 18 Gy 1St Radiation and Clinical Oncology Department, Maria Sklodowska‑ Curie boost after conventional radiotherapy, we show that ste- National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland. reotactic boost might also be applied in one fraction with Radiotherapy Planning Department, Maria Sklodowska‑ Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland. Tumor effective local control and acceptable tolerance. Unfortu - Pathology Department, Maria Sklodowska‑ Curie National Research Institute nately, the dynamic course of a second malignancy (lung of Oncology, Gliwice Branch, Gliwice, Poland. Ophthalmology Depar tment, cancer) led to death, similar to two cases in the Czech St. Barbara Provincial Hospital No 5, Sosnowiec, Poland. publication. Received: 17 October 2021 Accepted: 16 May 2022 In conclusion, the reported case is an example of a modern and effective approach of radiation therapy alone in the radical treatment of head and neck cancer. The expected direction of the development should involve References prospective trials with a large group of patients for evalu- 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality ating the efficacy and toxicity of SBRT boosts combined worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018. https:// with standard fractionation radiotherapy as well as with doi. org/ 10. 3322/ caac. 21492. systemic therapy, with particular emphasis on immuno- 2. Iyer NG, Tan DSW, Tan VK, et al. 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Radiation Oncology – Springer Journals
Published: Jun 3, 2022
Keywords: Squamous cell carcinoma; Stereotactic radiotherapy; Radiosurgery boost; Head and neck cancer
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