Biomedical subjects

Colin Field

Publications and source records attributed to Colin Field.

4 recordsLinked to original sources

PubMed2006

Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer.

OBJECTIVE: To explore the possible relationship between single nucleotide polymorphisms (SNP) in candidate genes encoding DNA damage recognition/repair/response and steroid metabolism proteins with respect to clinical radiation toxicity in a retrospective cohort of patients previously treated with three-dimensional conformal radiotherapy (3-DCRT) for prostate cancer. EXPERIMENTAL DESIGN: One hundred twenty-four patients with prostate cancer underwent 3-DCRT at our institution between September 1996 and December 2000. Of these, 83 consented for follow-up of blood sampling and SNP analysis. Twenty-eight patients were documented as having experienced grade >/=2 late bladder or rectal toxicity (scoring system of Radiation Therapy Oncology Group) on at least one follow-up visit. We analyzed 49 SNPs in BRCA1, BRCA2, ESR1, XRCC1, XRCC2, XRCC3, NBN, RAD51, RAD52, LIG4, ATM, BCL2, TGFB1, MSH6, ERCC2, XPF, NR3C1, CYP1A1, CYP2C9, CYP2C19, CYP3A5, CYP2D6, CYP11B2, and CYP17A1 genes using the Pyrosequencing technique. RESULTS: Significant univariate associations with late rectal or bladder toxicity (grade >/=2) were found for XRCC3 (A>G 5' untranslated region NT 4541), LIG4 (T>C Asp(568)Asp), MLH1 (C>T, Val(219)Ile), CYP2D6*4 (G>A splicing defect), mean rectal and bladder dose, dose to 30% of rectum or bladder, and age <60 years. On Cox multivariate analysis, significant associations with toxicity were found for LIG4 (T>C, Asp(568)Asp), ERCC2 (G>A, Asp(711)Asp), CYP2D6*4 (G>A, splicing defect), mean bladder dose >60 Gy, and dose to 30% of rectal volume >75 Gy. CONCLUSIONS: In this study, we identified SNPs in LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk for complications arising from radiation therapy in prostate cancer.

Aged↗

PubMed2005

Comparing step-and-shoot IMRT with dynamic helical tomotherapy IMRT plans for head-and-neck cancer.

PURPOSE: The goal of this planning study was to compare step-and-shoot intensity-modulated radiotherapy (IMRT) plans with helical dynamic IMRT plans for oropharynx patients on the basis of dose distribution. METHODS AND MATERIALS: Five patients with oropharynx cancer had been previously treated by step-and-shoot IMRT at the University Medical Centre Utrecht, The Netherlands, applying five fields and approximately 60-90 segments. Inverse planning was carried out using Plato, version 2.6.2. For each patient, an inverse IMRT plan was also made using Tomotherapy Hi-Art System, version 2.0, and using the same targets and optimization goals. Statistical analysis was performed by a paired t test. RESULTS: All tomotherapy plans compared favorably with the step-and-shoot plans regarding sparing of the organs at risk and keeping an equivalent target dose homogeneity. Tomotherapy plans in particular realized sharper dose gradients compared with the step-and-shoot plans. The mean dose to all parotid glands (n = 10) decreased on average 6.5 Gy (range, -4 to 14; p = 0.002). The theoretical reduction in normal tissue complication probabilities in favor of the tomotherapy plans depended on the parotid normal tissue complication probability model used (range, -3% to 32%). CONCLUSION: Helical tomotherapy IMRT plans realized sharper dose gradients compared with the clinically applied step-and shoot plans. They are expected to be able to reduce the parotid normal tissue complication probability further, keeping a similar target dose homogeneity.

Head and Neck Neoplasms↗

PubMed2004

Phenomenologic model describing flow reduction for parotid gland irradiation with intensity-modulated radiotherapy: evidence of significant recovery effect.

OBJECTIVE: To develop a model describing the relationship between the parotid gland radiation dose and salivary flow reduction. Salivary function was described by the "relative flow reduction" (RFR)-a continuous variable in contrast to the traditional binary response used in normal tissue complication probability estimations. METHODS AND MATERIALS: Twenty-three patients with squamous cell carcinoma of the head and neck who were treated with intensity-modulated radiotherapy (RT) were the subject of this study. Of these patients, 19 had sufficiently long follow-up to be eligible for analysis. All were treated with curative intent, most (14 of 19) in the postoperative setting. The planning objectives were to deliver a mean dose of 50, 60, or 70 Gy, respectively, to low-risk microscopic, high-risk microscopic, and gross disease areas, while maintaining a mean dose of < or =20 Gy to the spared portion of one or both parotid glands. The mean dose to all parotid glands (right and left) was 30.2 Gy. All submandibular glands received >50 Gy when not surgically removed. Whole-mouth saliva collections, including both stimulated and unstimulated saliva flow, were obtained before treatment and at regular intervals after RT. These measurements were converted to the RFR by comparing the posttreatment and pretreatment flow rates. Any follow-up flow rates greater than baseline were scored as 0 relative reduction. We used Lyman's model to relate the equivalent uniform dose to RFR at various points for each patient. The equivalent uniform dose was calculated using the linear quadratic model, with an assumed alpha/beta ratio of 3 Gy for the parotid gland. Measurements were modeled 1-3 months after RT (early) and >6 months after RT (late), and using the best and worst measurements, regardless of when measured. RESULTS: Fitting the Lyman model to RFR data of unstimulated flow revealed a statistically significant dose-complication relationship. We observed a stepwise reduction in flow, with the threshold dose D(50) at 2 Gy per fraction (D(50)) increasing from 12.4 Gy (early) to 43.9 Gy (late). For the worst and best flow measurements, the corresponding D(50) (2 Gy/fr) was 13.0 Gy and 40.1 Gy, respectively. For most stimulated flow measurements, a weak relationship was found between the RFR and equivalent uniform dose. In those cases, the model did not yield a statistically significant description of the data. However, in the case of late measurements, the relationship was statistically significant and similar to that seen in the unstimulated cases, with a D(50) (2 Gy/fr) of 47.5 Gy. CONCLUSION: We observed a strong relationship between the generalized mean parotid gland dose and RFR. The threshold dose increased markedly between the early and late measurements, indicating a statistically significant recovery effect in this tissue. Compared with unstimulated flow, the RFR for stimulated flow was not described as well by the model, because the effect of the stimulant was not included in the model.

Carcinoma, Squamous Cell↗

PubMed2004

A TCP-NTCP estimation module using DVHs and known radiobiological models and parameter sets.

Radiotherapy treatment plan evaluation relies on an implicit estimation of the tumor control probability (TCP) and normal tissue complication probability (NTCP) arising from a given dose distribution. A potential application of radiobiological modeling to radiotherapy is the ranking of treatment plans via a more explicit determination of TCP and NTCP values. Although the limited predictive capabilities of current radiobiological models prevent their use as a primary evaluative tool, radiobiological modeling predictions may still be a valuable complement to clinical experience. A convenient computational module has been developed for estimating the TCP and the NTCP arising from a dose distribution calculated by a treatment planning system, and characterized by differential (frequency) dose-volume histograms (DDVHs). The radiobiological models included in the module are sigmoidal dose response and Critical Volume NTCP models, a Poisson TCP model, and a TCP model incorporating radiobiological parameters describing linear-quadratic cell kill and repopulation. A number of sets of parameter values for the different models have been gathered in databases. The estimated parameters characterize the radiation response of several different normal tissues and tumor types. The system also allows input and storage of parameters by the user, which is particularly useful because of the rapidly increasing number of parameter estimates available in the literature. Potential applications of the system include the following: comparing radiobiological predictions of outcome for different treatment plans or types of treatment; comparing the number of observed outcomes for a cohort of patient DVHs to the predicted number of outcomes based on different models/parameter sets; and testing of the sensitivity of model predictions to uncertainties in the parameter values. The module thus helps to amalgamate and make more accessible current radiobiological modeling knowledge, and may serve as a useful aid in the prospective and retrospective analysis of radiotherapy treatment plans.

Body Burden↗