Acute Normal Tissue Reactions in Head-and-Neck Cancer Patients Treated With IMRT: Influence of Dose and Association With Genetic Polymorphisms in DNA DSB Repair Genes

Werbrouck, Joke; Ruyck, Kim De; Duprez, Frédéric; Veldeman, Liv; Claes, Kathleen; Eijkeren, M. Van; Boterberg, Tom; Willems, Petra; Vral, Anne; Neve, Wilfried De; Thierens, Hubert

doi:10.1016/j.ijrobp.2008.08.073

Cited by 122 publications

(101 citation statements)

References 25 publications

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“…Recent studies suggest that DNA polymorphisms may be associated with the occurrence of the adverse effects of RT. 46 One promising avenue would be to explore whether the genetic factors associated with the adverse effects of RT would improve our predictive model.…”

Section: Weight Loss In Head Andmentioning

confidence: 99%

Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer

Nourissat

Bairati

Samson

et al. 2010

Cancer

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BACKGROUND:The purpose of the study was to identify predictors of weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer. METHODS: This study was conducted as part of a phase 3 chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Their baseline characteristics, including lifestyle habits, diet, and quality of life, were assessed as potential predictors. Predictors were identified using multiple linear regressions. The reliability of the model was assessed by bootstrap resampling. A receiver operating characteristics curve was generated to estimate the model's accuracy in predicting critical weight loss (!5%). RESULTS: The mean weight loss was 2.2 kg (standard deviation, 3.4). Five factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P<.001), higher pre-RT body weight (P<.001), stage II disease (P ¼ .002), dysphagia and/or odynophagia before RT (P ¼ .001), and a lower Karnofsky performance score (P ¼ .028). There was no association with pre-RT lifestyle habits, diet, or quality of life. The bootstrapping method confirmed the reliability of this predictive model. The area under the curve was 71.3% (95% confidence interval, 65.8-76.9), which represents an acceptable ability of the model to predict critical weight loss. CONCLUSIONS: These results could be useful to clinicians for screening patients with early stage HN cancer treated by RT who require special nutritional attention. Cancer 2010;116:2275-83.

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Section: Weight Loss In Head Andmentioning

confidence: 99%

Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer

Nourissat

Bairati

Samson

et al. 2010

Cancer

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“…Dental fillings are a known factor that can exacerbate mucosal toxicity since it generates unpredictable scattering of the radiation and compromises the accuracy of the dose calculation to the adjacent sites due to the imaging artifact that is produced by these fillings on CT scan 6, 7. Several studies3, 4, 5, 11, 12, 13 have proposed dose and volumetric guidelines to reduce OM by treatment planning intervention but none of them has specifically focused on the effect of dental fillings nor investigated whether it is feasible to optimize the IMRT plan based on such guidelines in vivo. We frequently observe OM on the lateral tongue in patients with dental fillings and this site is also known to be more sensitive to radiation/chemotherapy‐induced mucositis compared to areas of keratinized oral mucosa such as the dorsal tongue, hard palate, and gingiva 8.…”

Section: Discussionmentioning

confidence: 99%

“…Limitation of this study includes small sample size, short follow up period and lack of additional information that might affect the onset and severity of mucositis, such as comorbidity, social habits30 and genetic predispositions 4…”

Section: Discussionmentioning

confidence: 99%

“…However, IMRT plans apply multiple radiation fields and can increase total irradiated volume when compared to less conformal radiation techniques 3. Several studies have shown that increased irradiated volume of oral cavity from IMRT can alter the expected toxicity of the treatment such as the rate of acute OM 3, 4. Narayan et al5 have shown that if the estimated mean dose to the buccal mucosa (as measured by dosimeters) was kept ≤32 Gy over the course of the radiation, only mild mucositis was noticed; however, if the dose exceeded 39 Gy, most patients developed grade (Gr) 2 OM.…”

Section: Introductionmentioning

confidence: 99%

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Feasibility of optimizing intensity‐modulated radiation therapy plans based on measured mucosal dose adjacent to dental fillings and toxicity outcomes

Seol

Aggarwal

Eyben

et al. 2018

J Applied Clin Med Phys

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We prospectively investigated the feasibility of IMRT treatment plan optimization based on dosimeter measurements of lateral tongue mucosal dose adjacent to the dental fillings and evaluated dose‐toxicity relationship and factors affecting oral mucositis (OM) in head and neck cancer patients. Twenty‐nine head and neck cancer patients with metallic dental fillings who were scheduled to undergo fractionated external beam radiation therapy (RT) ± chemotherapy were enrolled. The lateral tongue dose was measured and if the calculated dose for the entire treatment was ≥35 Gy, a re‐plan was generated to reduce the lateral tongue mucosal dose. OM was graded weekly according to Common Terminology Criteria for Adverse Events version 4.0 and the patients completed the Oral Mucositis Weekly Questionnaire‐Head and Neck Cancer. The result showed that it was not feasible to optimize the IMRT plan based on measured tongue dose in most of the patients who needed re‐plan as re‐planning compromised the target coverage in 60% of these patients. The duration of grade (Gr) 2 OM was correlated with measured lateral tongue dose (P = 0.050). Concurrent cetuximab was significantly associated with faster onset of Gr2 OM than concurrent cisplatin (P = 0.006) and with longer duration of OM (P = 0.041) compared to concurrent cisplatin or IMRT‐alone. The pattern of reported pain over time was significantly different for each treatment type (RT and cetuximab, RT and cisplatin and RT‐alone) and depending on the dose level (P = 0.006). In conclusion, optimizing the IMRT plan based on measured lateral tongue dose was not feasible. Measured lateral tongue dose was significantly correlated with longer duration of OM ≥Gr2, and concurrent cetuximab was associated with earlier onset and longer duration of OM ≥Gr2.

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“…LIG4 is involved in dna repair and PSEN1, MAP4K2 and TP53 are apoptosis-related genes. liG4, ligase iV forms a complex with the x-ray repair cross complementing protein 4, and further interacts with the dna-dependent protein kinase (16). increases in this gene result in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Poloxamer 188 enhances apoptosis in a human leukemia cell line

Aoki¹,

Tamura²,

Ohyashiki³

et al. 2010

Mol Med Rep

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Abstract. Poloxamer block copolymers have been studied in multiple applications as drug delivery systems (ddS). These a-B-a amphiphilic block copolymers up-regulate the expression of selected genes in cells and alter genetic responses to antineoplastic agents in cancer. one example is poloxamer 188, also known as pluronic F68, which may be promising as a carrier in ddS. To clarify the possible mechanistic role of pluronic F68 in several leukemia cell lines, we examined whether pluronic F68-inducible factors were capable of causing apoptosis. The influence of pluronic F68 on the cell lines was examined using a comprehensive analysis. it was found that treatment of K562 cells with 6% pluronic F68 resulted in G 2 /M phase arrest of the cell cycle, followed by caspase activation and the accumulation of apoptotic cells. When used as a carrier in a ddS, pluronic F68 may provide a synergistic effect on the drug of interest. although the mechanisms behind the function of pluronic F68 are not fully understood, the results suggests that pluronic F68 may act as a useful carrier in ddS for the purpose of leukemia therapy.

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Acute Normal Tissue Reactions in Head-and-Neck Cancer Patients Treated With IMRT: Influence of Dose and Association With Genetic Polymorphisms in DNA DSB Repair Genes

Cited by 122 publications

References 25 publications

Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer

Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer

Feasibility of optimizing intensity‐modulated radiation therapy plans based on measured mucosal dose adjacent to dental fillings and toxicity outcomes

Poloxamer 188 enhances apoptosis in a human leukemia cell line

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