Biomedical subjects

Laura Happersett

Publications and source records attributed to Laura Happersett.

6 recordsLinked to original sources

PubMed2007

Reduced-order parameter optimization for simplifying prostate IMRT planning.

Intensity-modulated radiotherapy (IMRT) has become an effective tool for cancer treatment with radiation. However, even expert radiation planners still need to spend a substantial amount of time manually adjusting IMRT optimization parameters such as dose limits and costlet weights in order to obtain a clinically acceptable plan. In this paper, we describe two main advances that simplify the parameter adjustment process for five-field prostate IMRT planning. First, we report the results of a sensitivity analysis that quantifies the effect of each hand-tunable parameter of the IMRT cost function on each clinical objective and the overall quality of the resulting plan. Second, we show that a recursive random search over the six most sensitive parameters as an outer loop in IMRT planning can quickly and automatically determine parameters for the cost function that lead to a plan meeting the clinical requirements. Our experiments on a ten-patient dataset show that for 70% of the cases, we can automatically determine a plan in 10 min (on the average) that is either clinically acceptable or requires only minor adjustment by the planner. The outer-loop optimization can be easily integrated into a traditional IMRT planning system.

Algorithms↗

PubMed2005

Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer.

PURPOSE: Intensity-modulated radiation therapy (IMRT) enables highly conformal treatment for thyroid cancer (TC). In this study, we review outcomes/toxicity in a series of TC patients treated with IMRT. METHODS AND MATERIALS: Between July 2001 and January 2004, 20 nonanaplastic TC patients underwent IMRT. Mean age was 55. There were 3 T2 and 17 T4 patients. Sixteen patients had N1 disease. Seven patients had metastases before RT. Fifteen underwent surgery before RT. Radioactive iodine (RAI) and chemotherapy were used in 70% and 40%, respectively. Median total RT dose was 63 Gy. RESULTS: With two local failures, 2-year local progression-free rate was 85%. There were six deaths, with a 2-year overall survival rate of 60%. For patients with M0 disease, the 2-year distant metastases-free rate was 46%. The worst acute mucositis and pharyngitis was Grade 3 (n = 7 and 3, respectively). Two patients had Grade 3 acute skin toxicity and 2 had Grade 3 acute laryngeal toxicity. No significant radiation-related late effects were reported. CONCLUSIONS: IMRT for TC is feasible and effective in appropriately selected cases. Acute toxicity is manageable with proactive clinical care. Ideal planning target volume doses have yet to be determined. Additional patients and long-term follow-up are needed to confirm these preliminary findings and to clarify late toxicities.

Adolescent↗

PubMed2005

Methodology for biologically-based treatment planning for combined low-dose-rate (permanent implant) and high-dose-rate (fractionated) treatment of prostate cancer.

PURPOSE: The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning. METHODS AND MATERIALS: Patients treated with this regimen initially receive an I-125 implant prescribed to 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters (alpha, beta, potential doubling time for prostate cancer cells [T(pot)], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens. RESULTS: The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning. CONCLUSIONS: We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.

Algorithms↗

PubMed2003

Patterns of failure using a conformal radiation therapy tumor bed boost for medulloblastoma.

PURPOSE: To assess the patterns of failure for patients with medulloblastoma receiving a conformal tumor bed boost rather than a boost to the entire posterior fossa. PATIENTS AND METHODS: From 1994 to 2002, 32 consecutive patients with newly diagnosed medulloblastoma treated at Memorial Sloan-Kettering Cancer Center (New York, NY) received a conformal boost to the tumor bed in conjunction with craniospinal radiation therapy. Twenty-eight patients also received chemotherapy. The median age was 9 years (range, 3 to 34 years), and the male to female ratio was 3:1. Twenty-seven patients had standard-risk disease, and five patients had high-risk disease. Craniospinal doses ranged from 23.4 to 39.6 Gy, and total tumor bed doses ranged from 54 to 59.4 Gy. RESULTS: With a median follow-up of 56 months, six patients have relapsed; five relapsed outside of the posterior fossa, and one failed within the posterior fossa, outside of the high-dose boost volume. Five-year actuarial disease-free and overall survival rates were 84% and 85%, respectively. Freedom from posterior fossa failure was 100% and 86% at 5 and 10 years, respectively. Freedom from distant failure was 84% at 5 years, with a trend for improvement when full-dose craniospinal radiation (36 to 39.6 Gy) was used compared with a reduced dose (23.4 Gy) of radiation (100% v 63%, respectively; P =.06). No other predictive variables were identified. CONCLUSION: Conformal treatment to the tumor bed allows for significant sparing of critical structures. The posterior fossa failure rate in this series is similar to that reported when the entire posterior fossa is treated. This approach should be investigated further in a phase III trial.

Adolescent↗

PubMed2003

A study of the effects of internal organ motion on dose escalation in conformal prostate treatments.

BACKGROUND AND PURPOSE: To assess the effect of internal organ motion on the dose distributions and biological indices for the target and non-target organs for three different conformal prostate treatment techniques. MATERIALS AND METHODS: We examined three types of treatment plans in 20 patients: (1) a six field plan, with a prescribed dose of 75.6 Gy; (2) the same six field plan to 72 Gy followed by a boost to 81 Gy; and (3) a five field plan with intensity modulated beams delivering 81 Gy. Treatment plans were designed using an initial CT data set (planning) and applied to three subsequent CT scans (treatment). The treatment CT contours were used to represent patient specific organ displacement; in addition, the dose distribution was convolved with a Gaussian distribution to model random setup error. Dose-volume histograms were calculated using an organ deformation model in which the movement between scans of individual points interior to the organs was tracked and the dose accumulated. The tumor control probability (TCP) for the prostate and proximal half of seminal vesicles (clinical target volume, CTV), normal tissue complication probability (NTCP) for the rectum and the percent volume of bladder wall receiving at least 75 Gy were calculated. RESULTS: The patient averaged increase in the planned TCP between plan types 2 and 1 and types 3 and 1 was 9.8% (range 4.9-12.5%) for both, whereas the corresponding increases in treatment TCP were 9.0% (1.3-16%) and 8.1% (-1.3-13.8%). In all patients, plans 2 and 3 (81 Gy) exhibited equal or higher treatment TCP than plan 1 (75.6 Gy). The maximum treatment NTCP for rectum never exceeded the planning constraint and percent volume of bladder wall receiving at least 75 Gy was similar in the planning and treatment scans for all three plans. CONCLUSION: For plans that deliver a uniform prescribed dose to the planning target volume (PTV) (plan 1), current margins are adequate. In plans that further escalate the dose to part of the PTV (plans 2 and 3), in a fraction of the cases the CTV dose increase is less than planned, yet in all cases the TCP values are higher relative to the uniform dose PTV (plan 1). Doses to critical organs remain within the planning criteria.

Humans↗

PubMedDate not supplied

Intensity-modulated radiotherapy.

Intensity-modulated radiotherapy represents a recent advancement in conformal radiotherapy. It employs specialized computer-driven technology to generate dose distributions that conform to tumor targets with extremely high precision. Treatment planning is based on inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying intensities across the beam section. Combinations of intensity-modulated fields produce custom-tailored conformal dose distributions around the tumor, with steep dose gradients at the transition to adjacent normal tissues. Thus far, data have demonstrated improved precision of tumor targeting in carcinomas of the prostate, head and neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose escalation to previously unattainable levels. This experience indicates that intensity-modulated radiotherapy represents a significant advancement in the ability to deliver the high radiation doses that appear to be required to improve the local cure of several types of tumors. The integration of new methods of biologically based imaging into treatment planning is being explored to identify tumor foci with phenotypic expressions of radiation resistance, which would likely require high-dose treatments. Intensity-modulated radiotherapy provides an approach for differential dose painting to selectively increase the dose to specific tumor-bearing regions. The implementation of biologic evaluation of tumor sensitivity, in addition to methods that improve target delineation and dose delivery, represents a new dimension in intensity-modulated radiotherapy research.

Abdominal Neoplasms↗