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. 2024 Dec 23;16(24):4283.
doi: 10.3390/cancers16244283.

Clinical Introduction of Stem Cell Sparing Radiotherapy to Reduce the Risk of Xerostomia in Patients with Head and Neck Cancer

Maria I van Rijn-Dekker  1 , Arjen van der Schaaf  1 , Sanne W Nienhuis  1 , Antoinette S Arents-Huls  2 , Rachel B Ger  3 , Olga Hamming-Vrieze  4 , Frank J P Hoebers  5 , Mischa de Ridder  6 , Sabrina Vigorito  7 , Ellen M Zwijnenburg  8 , Johannes A Langendijk  1 , Peter van Luijk  1 , Roel J H M Steenbakkers  1
Affiliations

Clinical Introduction of Stem Cell Sparing Radiotherapy to Reduce the Risk of Xerostomia in Patients with Head and Neck Cancer

Maria I van Rijn-Dekker et al. Cancers (Basel). .

Abstract

Background/objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice.

Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients. Shifts in mean dose to the SCR regions (Dmean,SCR) and other organs at risk and their estimated impact on normal tissue complication probability (NTCP) for side-effects were compared using Wilcoxon signed-rank test. A multicenter study was performed (eight institutions, three patients) to test the generalizability of SCS-RT using the Friedman test.

Results: Using photons, Dmean,SCR was reduced with median 4.1/3.5 Gy for ipsilateral/contralateral (p < 0.001). The largest reductions were when the SCR regions overlapped less with target volumes. Subsequently, NTCPs for xerostomia decreased (p < 0.001). Using protons, Dmean,SCR was also reduced (2.2/1.9 Gy for ipsilateral/contralateral, p < 0.002). Nevertheless, SCS-RT did not further decrease NTCPs for xerostomia (p > 0.17). Target coverage and prevention of other side-effects were not compromised. However, increased mean oral cavity dose was observed in some patients. Lastly, in the multicenter study Dmean,SCR could be reduced by slightly adjusting the standard optimization. Contralateral Dmean,SCR reductions differed between centers (p = 0.01), which was attributed to differences in ST-RT plans.

Conclusions: Stem cell sparing radiotherapy can be clinically introduced by making small adjustments to the optimization strategy and can reduce the risk of xerostomia.

Keywords: head and neck cancer; parotid gland stem cells; stem cell sparing radiotherapy; xerostomia.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Dose shifts with photon (step 2) and proton therapy (step 4). Abbreviations: CL = contralateral (i.e., receiving lowest dose); IL = ipsilateral (i.e., receiving highest dose); non-SCR = remaining parotid gland tissue (i.e., parotid gland minus SCR region); PCM = pharyngeal constrictor muscle; RT = radiotherapy; SCR = stem cell rich; SCS = stem cell sparing; ST = standard. * Significant according to Wilcoxon signed-rank test (significance level of p < 0.05).
Figure 2
Figure 2
Estimated clinical impact of SCSRT with photon therapy on several xerostomia outcomes. This figure depicts the NTCP differences (i.e., NTCP in ST-RT plan minus NTCP in SCS-RT plan) for several xerostomia outcomes. The NTCPs were calculated using the models developed by van Rijn-Dekker et al. [10]. The lines depict the number of patients in which the NTCP was decreased by at least 1% (yellow), 2% (red), and 3% (blue). Abbreviations: NTCP = normal tissue complication probability; SCS = stem cell sparing; ST = standard; RT = radiotherapy.
Figure 3
Figure 3
Multicenter study (step 3): achieved dose reductions in the SCR regions. Abbreviations: RT = radiotherapy; SCR = stem cell rich; SCS = stem cell sparing; ST = standard. * Significant according to Friedman test (significance level of p < 0.05)
Figure 4
Figure 4
Application of SCS-RT by slightly adjusting the centers’ own standard treatment optimizations. Examples from the different dose distributions of the SCS-RT plan from the different centers (orange = 66.5 Gy; green = 51.54 Gy; light blue = 40 Gy; dark blue = 30 Gy; purple = 20 Gy; white = 10 Gy) demonstrating that each center was able to reduce mean SCR region dose. The following OARs were delineated: SCR regions (red), parotid glands (green), oral cavity (pink), and brain (black). Abbreviations: Gy = Gray; RT = radiotherapy; SCR = stem cell rich; SCS = stem cell sparing.
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