Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy
ABSTRACT Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NV symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose (p = 0.0025) and area postrema mean dose (p = 0.004); however, both failed to meet statistical significance at the p ≤ 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients (p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.
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ABSTRACT: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs, and weightings should be considered for dose sparing during optimization in the treatment planning of IMRT.International journal of radiation oncology, biology, physics 01/2012; 84(1):176-82. DOI:10.1016/j.ijrobp.2011.10.010 · 4.18 Impact Factor
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ABSTRACT: Objective This study aimed to correlate planned dose to the nausea center (NC)—area postrema (AP) and dorsal vagal complex (DVC)—with nausea and vomiting symptoms in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiation therapy (IMRT) without chemotherapy. We also investigated whether it was possible to reduce doses to the NC without significant degradation of the clinically accepted treatment plan. Methods From November 2004 to April 2009, 37 OPC patients were treated with definitive or adjuvant IMRT without chemotherapy. Of these, only 23 patients had restorable plans and were included in this analysis. We contoured the NC with the assistance of an expert, board-certified neuroradiologist. We searched for correlation between the delivered dose to the NC and patient-reported nausea and vomiting during IMRT. We used one-paired two-sample t test assuming equal variances to compare differences in dose to NC between symptomatic and asymptomatic patients. We then replanned each case to determine if reduced dose to the NC could be achieved without compromising coverage to target volumes, increasing unwarranted hotspots, or increasing dose to surrounding critical normal tissues. Results Acute symptoms of nausea were as follows: grade 0 (n = 6), grade 1 (n = 13), grade 2 (n = 3), and grade 3 (n = 1). Patients with no complaints of nausea had a median dose to the DVC of 34.2 Gy (range 4.6–46.6 Gy) and AP of 32.6 Gy (range 7.0–41.4 Gy), whereas those with any complaints of nausea had a median DVC dose of 40.4 Gy (range 19.3–49.4 Gy) and AP dose of 38.7 Gy (range 16.7–46.8 Gy) (p = 0.04). Acute vomiting was as follows: grade 0 (n = 17), grade 1 (n = 4), grade 2 (n = 1), and grade 3 (n = 1). There was no significant difference in DVC or AP dose among those with and without vomiting symptoms (p = 0.28). Upon replanning of each case to minimize dose to the NC, we were, on average, able to reduce the radiation dose to AP by 18 % and DVC by 17 %, while the average dose variations to the planning target volume (PTV) coverage, brainstem, cord, temporal lobes, and cochlea were never greater than 3 %. Hotspots increased by 2 % for three patients while hotspots for the remaining patients were less than 2 % variation. Conclusion For OPC cancer patients treated with IMRT without chemotherapy, dose to AP and DVC may be associated with development of nausea. We were able to show that reducing doses substantially to the NC is achievable without significant alteration of the clinically accepted plan and may reduce the incidence and grade of nausea. As symptoms of nausea can be devastating to patients, one can consider routine contouring and constraining of the NC to minimize chances of having this complication.11/2012; 84(3). DOI:10.1007/s13566-013-0094-7
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ABSTRACT: Purpose To investigate the role of dose to the dorsal vagal complex (DVC) as an emetic stimulus in head-and-neck cancer patients treated with intensity modulated radiation therapy but without chemotherapy. Methods and materials Seventy consecutively treated patients were analyzed for factors associated with nausea. The DVC was contoured on treatment planning scans using a previously published template and mean dose to the structure was analyzed for dose response. Results Nausea occurred in 26 of 70 patients (37%). Two patients (3%) experienced grade 2 nausea, with the remainder having grade 1 nausea. On univariate analysis, dose to the DVC, age, and T-stage were the only significant predictors of nausea. The highest quartile of dose to the DVC (> 3000 cGy) was associated with an incidence of nausea of 67% compared with less than 30% in each of the other 3 quartiles (P = .0255). Conclusions Dose to the DVC of the brainstem appears to correlate with radiation-induced nausea and vomiting. Attentive treatment planning efforts can reduce dose to this critical structure and hopefully minimize the risk of nausea.01/2013; 4(4). DOI:10.1016/j.prro.2013.08.003