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Radiotherapy-related changes in serum proteome patterns of head and neck cancer patients; the effect of low and medium doses of radiation delivered to large volumes of normal tissue.

ABSTRACT: BACKGROUND: Conformal intensity-modulated radiation therapy (IMRT) involves irradiation of large volume of normal tissue with low and medium doses, biological relevance of which is not clear yet. Serum proteome features were used here to study the dose-volume effects in patients irradiated with IMRT due to head and neck cancer. METHODS: Blood samples were collected before and during RT, and also about one month and one year after the end of RT in a group of 72 patients who received definitive treatment. Serum proteome profiles were analyzed using MALDI-ToF mass spectrometry in 800-14,000 Da range. RESULTS: Major changes in serum proteome profiles were observed between pre-treatment samples and samples collected one month after RT. Radiation-related changes in serum proteome features were affected by low-to-medium doses delivered to a large fraction of body mass. Proteome changes were associated with intensity of acute radiation toxicity, indicating collectively that RT-related features of serum proteome reflected general response of patient's organism to irradiation. However, short-term dose-related changes in serum proteome features were not associated significantly with the long-term efficacy of the treatment. CONCLUSIONS: The effects of low and medium doses of radiation have been documented at the level of serum proteome, which is a reflection of the patient's whole body response.

SUBMITTER: Widlak P

PROVIDER: S-EPMC4235198 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Radiotherapy-related changes in serum proteome patterns of head and neck cancer patients; the effect of low and medium doses of radiation delivered to large volumes of normal tissue.

Widłak Piotr P Pietrowska Monika M Polańska Joanna J Rutkowski Tomasz T Jelonek Karol K Kalinowska-Herok Magdalena M Gdowicz-Kłosok Agnieszka A Wygoda Andrzej A Tarnawski Rafał R Składowski Krzysztof K

Journal of translational medicine 20131205

<h4>Background</h4>Conformal intensity-modulated radiation therapy (IMRT) involves irradiation of large volume of normal tissue with low and medium doses, biological relevance of which is not clear yet. Serum proteome features were used here to study the dose-volume effects in patients irradiated with IMRT due to head and neck cancer.<h4>Methods</h4>Blood samples were collected before and during RT, and also about one month and one year after the end of RT in a group of 72 patients who received ...[more]

PMID: 24304975

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Project description:Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses.In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative delivered doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy.Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were -4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose-effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments.After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose-saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were observed at first treatment, indicating potential benefit for more complex setup corrections or adaptive interventions in the minority of patients with large deviations detected early by CBCT.

Project description:Radiotherapy (RT) is frequently used in the treatment of head and neck cancer, but different side-effects are frequently reported, including a higher frequency of radiation-related caries, what may be consequence of direct radiation to dental tissue. The intensity-modulated radiotherapy (IMRT) was developed to improve tumor control and decrease patient's morbidity by delivering radiation beams only to tumor shapes and sparing normal tissue. However, teeth are usually not included in IMRT plannings and the real efficacy of IMRT in the dental context has not been addressed. Therefore, the aim of this study is to assess whether IMRT delivers lower radiation doses to dental structures than conformal 3D radiotherapy (3DRT).Radiation dose delivery to dental structures of 80 patients treated for head and neck cancers (oral cavity, tongue, nasopharynx and oropharynx) with IMRT (40 patients) and 3DRT (40 patients) were assessed by individually contouring tooth crowns on patients' treatment plans. Clinicopathological data were retrieved from patients' medical files.The average dose of radiation to teeth delivered by IMRT was significantly lower than with 3DRT (p?=?0.007); however, only patients affected by nasopharynx and oral cavity cancers demonstrated significantly lower doses with IMRT (p?=?0.012 and p?=?0.011, respectively). Molars received more radiation with both 3DRT and IMRT, but the latter delivered significantly lower radiation in this group of teeth (p?<?0.001), whereas no significant difference was found for the other dental groups. Maxillary teeth received lower doses than mandibular teeth, but only IMRT delivered significantly lower doses (p?=?0.011 and p?=?0.003). Ipsilateral teeth received higher doses than contralateral teeth with both techniques and IMRT delivered significantly lower radiation than 3DRT for contralateral dental structures (p?<?0.001).IMRT delivered lower radiation doses to teeth than 3DRT, but only for some groups of patients and teeth, suggesting that this decrease was more likely due to the protection of other high risk organs, and was not enough to remove teeth from the zone of high risk for radiogenic disturbance (>30Gy).

Project description:PurposeTo develop a deep learning model that generates consistent, high-quality lymph node clinical target volumes (CTV) contours for head and neck cancer (HNC) patients, as an integral part of a fully automated radiation treatment planning workflow.Methods and materialsComputed tomography (CT) scans from 71 HNC patients were retrospectively collected and split into training (n = 51), cross-validation (n = 10), and test (n = 10) data sets. All had target volume delineations covering lymph node levels Ia through V (Ia-V), Ib through V (Ib-V), II through IV (II-IV), and retropharyngeal (RP) nodes, which were previously approved by a radiation oncologist specializing in HNC. Volumes of interest (VOIs) about nodal levels were automatically identified using computer vision techniques. The VOI (cropped CT image) and approved contours were used to train a U-Net autosegmentation model. Each lymph node level was trained independently, with model parameters optimized by assessing performance on the cross-validation data set. Once optimal model parameters were identified, overlap and distance metrics were calculated between ground truth and autosegmentations on the test set. Lastly, this final model was used on 32 additional patient scans (not included in original 71 cases) and autosegmentations visually rated by 3 radiation oncologists as being "clinically acceptable without requiring edits," "requiring minor edits," or "requiring major edits."ResultsWhen comparing ground truths to autosegmentations on the test data set, median Dice Similarity Coefficients were 0.90, 0.90, 0.89, and 0.81, and median mean surface distance values were 1.0 mm, 1.0 mm, 1.1 mm, and 1.3 mm for node levels Ia-V, Ib-V, II-IV, and RP nodes, respectively. Qualitative scoring varied among physicians. Overall, 99% of autosegmented target volumes were either scored as being clinically acceptable or requiring minor edits (ie, stylistic recommendations, <2 minutes).ConclusionsWe developed a fully automated artificial intelligence approach to autodelineate nodal CTVs for patients with intact HNC. Most autosegmentations were found to be clinically acceptable after qualitative review when considering recommended stylistic edits. This promising work automatically delineates nodal CTVs in a robust and consistent manner; this approach can be implemented in ongoing efforts for fully automated radiation treatment planning.

Dataset Information

Radiotherapy-related changes in serum proteome patterns of head and neck cancer patients; the effect of low and medium doses of radiation delivered to large volumes of normal tissue.

Publications

Radiotherapy-related changes in serum proteome patterns of head and neck cancer patients; the effect of low and medium doses of radiation delivered to large volumes of normal tissue.

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