Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination.
Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin.



A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV56) were evaluated to identify the predictors for NTCP improvement.



With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV56 >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV56 >22% predicted benefit with C70 (P<.01).



PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the percentage of overlap of the PTV with organs at risk can predict which patients will benefit and inform future clinical trial design.
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Stuart E
SE
Samuels
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Avraham
A
Eisbruch
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Karen
K
Vineberg
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Jae
J
Lee
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Choonik
C
Lee
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Martha M
MM
Matuszak
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Randall K
RK
Ten Haken
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address: kbrock@med.umich.edu.
Kristy K
KK
Brock
D003198:Computer Simulation; D004066:Digestive System Diseases / Q000453:epidemiology* / Q000517:prevention & control; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015994:Incidence; D008824:Michigan / Q000453:epidemiology; D015233:Models, Statistical; D059351:Organ Sparing Treatments / Q000379:methods* / Q000706:statistics & numerical data; D058958:Organs at Risk / Q000528:radiation effects; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D011832:Radiation Injuries / Q000453:epidemiology* / Q000517:prevention & control; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D047368:Tumor Burden / Q000528:radiation effects