Higher Tumor Control Probability Research Articles

Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses (≤22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.

Choline PET based dose-painting in prostate cancer--modelling of dose effects.

BackgroundSeveral randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed.MethodsBased on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed.ResultsUsing schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition).DiscussionAlthough a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the assumption of high detection rates and low initial TCP values the TCP gain has been shown to be relevant.ConclusionsBased on the employed assumptions, specific dose escalation to choline PET positive areas within the prostate may increase the local control rates. Due to the lack of exact PET sensitivity and prostate α/β parameter, no firm conclusions can be made. Small variations may completely abrogate the clinical benefit of a SIB based on choline PET imaging.

Design of an accelerator-based neutron source for neutron capture therapy

The boron neutron capture therapy is mainly suited in the treatment of some tumor kinds which revealed ineffective to the traditional radiotherapy. In order to take advantage of such a therapeutic modality in hospital environments, neutron beams of suitable energy and flux levels provided by compact size facilities are needed. The advantages and drawbacks of several neutron beams are here analysed in terms of therapeutic gains. In detail the GEANT-3/MICAP simulations show that high tumor control probability, with sub-lethal dose at healthy tissues, can be achieved by using neutron beams of few keV energy having a flux of about 10 9 neutrons/(cm 2 s). To produce such a neutron beam, the feasibility of a proton accelerator is investigated. In particular an appropriate choice of the radiofrequency parameters (modulation, efficiency of acceleration, phase shift, etc.) allows the development of relatively compact accelerators, having a proton beam current of 30 mA and an energy of 2 MeV, which could eventually lead to setting up of hospital-based neutron facilities.

Nuclear reactions induced by deuterons and their applicability to skin tumor treatment through BNCT

In this work the D(d,n) 3He and 9Be(d,n) 10B reactions have been studied in a low-energy regime as neutron sources for skin tumor treatment in the frame of accelerator-based BNCT (AB-BNCT). The total neutron production and the energy and angular distributions for each reaction at different bombarding energies and for the thick targets considered (TiD 2, Be) have been determined using the available data in the literature. From this information, a feasibility study has been performed by means of MCNP simulations. The thermal, epithermal and fast neutron fluxes and doses at skin tumor positions (loaded with 40 ppm 10B) which are located on a whole-body human phantom have been simulated for different D 2O moderator depths. The best-case performance shows that a high tumor control probability (TCP) of 99% corresponding to a weighted dose in tumor of 40 Gy can be reached at the tumor position keeping the weighted dose in healthy tissue below 12.5 Gy, by means of the 9Be(d,n) 10B reaction at 1.1 MeV for a deuteron current of 20 mA and a 30 cm D 2O moderator in 52 min. The availability of low-energy neutrons in the 9Be(d,n) 10B reaction from the population of excited levels between 5.1 to 5.2 MeV in 10B and the convenience of a thin beryllium target are discussed. As a complement concerning alternatives to the Li(metal) + p reaction, the neutron yield of refractory lithium compounds (LiH, Li 3N and Li 2O) were calculated and compared with a Li metal target.

Definitive radiotherapy in the management of paragangliomas arising in the head and neck: A 35‐year experience

An evaluation of the treatment results for 104 patients with 121 paragangliomas of the temporal bone, carotid body, and/or glomus vagale who were treated with radiation therapy (RT) at the University of Florida between 1968 and 2004. Eighty-nine paragangliomas (86%) were treated with conventional megavoltage techniques, 15 (14%) patients with stereotactic fractionated radiation therapy, 6 (6%) patients with stereotactic radiosurgery (SRS), and 11 (11%) patients with intensity-modulated radiation therapy (IMRT). There were 6 local recurrences. One recurrence was salvaged with additional RT. The actuarial local control and cause-specific survival rates at 10 years were 94% and 95%. The overall local control rate for all 121 lesions was 95%; the ultimate local control rate was 96%. The incidence of treatment-related complications was low. Fractionated RT offers a high probability of tumor control with minimal risks for patients with paragangliomas of the temporal bone and neck.

Assessment of tumor control probability for high-dose-rate interstitial brachytherapy implants

Summary Aim The study was designed to propose a novel concept of biologically effective equivalent uniform dose to calculate tumor control probability for HDR implants. Materials and Methods The expression of biologically effective equivalent uniform dose was derived for non-uniform dose distribution in HDR implants using quality indices and voxel-based tumor control probability. Results The results of this study show that high dose regions of the implant have higher tumor control probability. But these regions may also have a large number of normal cells and consequently may lead to severe normal tissue complications. If tumor coverage was not proper then the overall tumor control probability would be low and might result in tumor recurrence. Higher values of external volume index, dose non-uniformity ratio and overdose volume index were related to higher normal tissue complication rates outside and inside the implants. Conclusion The present concept may provide an alternative approach to calculate tumor control probability for HDR implants.

High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

Paragangliomas of the Head and Neck Treated With External-Beam Radiotherapy

To evaluate the results of treatment for 104 patients with 121 paragangliomas of the temporal bone, carotid body, or glomus vagale who were treated with radiation therapy (RT) alone or after subtotal resection at the University of Florida between 1968 and 2004. Eighty-nine (86%) patients were treated with conventional megavoltage techniques, 15 (14%) patients with stereotactic fractionated radiotherapy (SRT), 6 (6%) patients with stereotactic radiosurgery (SRS), and 11 (11%) patients with IMRT. One hundred four lesions were previously untreated, whereas 17 had undergone prior treatment (surgery, 14 lesions; RT, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All 3 patients who received prior RT had been treated at other institutions. Four (4%) patients had metastatic neck disease at presentation. Patients had minimum follow-up times as follows: 2 years, 104 patients (100%); 5 years, 78 patients (75%); 10 years, 42 patients (40%); 15 years, 21 patients (20%); 20 years, 12 patients (11%); 25 years, 5 patients (5%); and 30 years, 4 patients (4%). There were 6 local recurrences at 0.7 years, 1.4 years, 2.6 years, 4.5 years, 5.2 years, and 8.2 years. Five were in glomus jugulare tumors and one was in a carotid body tumor. Two of the six recurrences had been treated previously at other institutions with RT and/or surgery. A third recurrence occurred after a geographic miss with stereotactic radiosurgery (SRS). Treatment for a fourth recurrence was discontinued against medical advice before receiving the prescribed dose. There were, therefore, only 2 failures in 104 previously untreated lesions receiving the prescribed course of RT. One recurrence was successfully salvaged with additional RT. Salvage attempts in 2 other patients were unsuccessful. The actuarial local-control probability and cause-specific survival at 10 years were 94% and 95%, respectively. The overall crude local-control rate for all 121 lesions was 95%, with an ultimate local-control rate of 96%. The incidence of grade 1 and 2 treatment-related complications was low. There were no severe treatment complications. Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone and neck.

The current status of FDG–PET in tumour volume definition in radiotherapy treatment planning

Positron emission tomography (PET) scan, mainly using 18 F-fluoro-deoxyglucose (FDG) as a tracer, is currently widely accepted as a diagnostic tool in oncology. It may lead to a change in staging and therefore in treatment management. PET can also be used to define the target volume in radiation treatment planning and to evaluate treatment response. In this review, we focused on issues concerning the role of PET in target volume delineation, both for the primary tumour and regional lymph nodes. A literature search was performed using MEDLINE. Furthermore, the following questions were addressed: does PET allow accurate tumour delineation and does it improve the outcome of radiotherapy, in terms of reduced toxicity or a higher tumour control probability? Combined computer tomography (CT) and PET information seems to influence target volume delineation. Using (CT-) PET scan, interobserver variability is being reduced. Only few studies compared delineation based on PET with pathologic examination, showing a complex relation. Preliminary results concerning incorporation of PET information in to target volume delineation varies in different tumour sites. In the field of lung cancer, incorporation of PET seems to improve tumour coverage and spare normal tissues, which may lead to less toxicity or the possibility to escalate dose. In oesophageal cancer and in lymphoma, PET scan can be used to include PET positive lymph nodes in the target volume. In most other tumour sites not enough data are currently available to draw definitive conclusions about the role of PET in radiation treatment planning.

How does performance of ultrasound tissue typing affect design of prostate IMRT dose-painting protocols?

To investigate how the performance characteristics of ultrasound tissue typing (UTT) affect the design of a population-based prostate dose-painting protocol. The performance of UTT is evaluated using the receiver operating characteristic curve. As the imager's sensitivity increases, more tumors are detected, but the specificity worsens, causing more false-positive results. The UTT tumor map, obtained with a specific sensitivity and specificity setup, was used with the patient's CT image to guide intensity-modulated radiotherapy (IMRT) planning. The optimal escalation dose to the UTT positive region, as well as the safe dose to the negative background, was obtained by maximizing the uncomplicated control (i.e., a combination of tumor control probability and weighted normal tissue complication probability). For high- and low-risk tumors, IMRT plans guided by conventional ultrasound or UTT with a one-dimensional or two-dimensional spectrum analysis technique were compared with an IMRT plan in which the whole prostate was dose escalated. For all imaging modalities, the specificity of 0.9 was chosen to reduce complications resulting from high false-positive results. If the primary tumors were low risk, the IMRT plans guided by all imaging modalities achieved high tumor control probability and reduced the normal tissue complication probability significantly compared with the plan with whole gland dose escalation. However, if the primary tumors were high risk, the accuracy of the imaging modality was critical to maintain the tumor control probability and normal tissue complication probability at acceptable levels. The performance characteristics of an imager have important implications in dose painting and should be considered in the design of dose-painting protocols.

How Does the Performance of Ultrasound Tissue Typing Affect the Design of Prostate IMRT Dose Painting Protocols?

Purpose/Objective: Ultrasound Tissue Typing (UTT) can be used to obtain the tumor map in prostate, thus providing guidance in IMRT dose painting. In this study we investigated the implications of the UTT′s performance characteristics on the design of a population based prostate dose painting protocol. Materials/Methods: The performance of UTT is evaluated via the receiver operating characteristic curve, which is a plot of the imaging modality′s sensitivity (TPF) versus false-positive fraction (FPF, i.e., 1-specificity). As sensitivity increases, more tumors are detected, although specificity worsens, causing more false positives. The UTT tumor map obtained with a specific sensitivity and specificity setup is fused with the patient′s CT image to guide IMRT planning. The optimal escalation dose to the tumor positive region identified by UTT, as well as the safe dose to the identified tumor negative background was obtained by maximizing uncomplicated control, which is a combination of tumor control probability (TCP), and weighted normal tissue complication probability (NTCP). IMRT plans guided by B-mode Ultrasound and UTT are compared to the IMRT plan in which the whole prostate gland is dose escalated to the same TCP level. Results: All imaging modalities are configured to have a specificity of 0.9 to reduce complications due to high false positives. As illustrated in the following table, if the primary tumors are at the low-risk stage, IMRT plan guided by all imaging modalities can achieve high TCP while reducing NTCP significantly compared to the plan with whole gland escalation. However, if the primary tumors are at the high-risk stage, accuracy of the imaging modality is the key of maintaining both TCP and NTCP at the acceptable level. Conclusions: Performance characteristics of an imager as described by sensitivity and specificity has important implications in prostate dose painting, and should be considered in the future design of dose painting protocols. Tabled 11 Blind represents the scenario that the whole prostate gland is dose escalated. 2 UTT_1D and UTT_2D represent ultrasound tissue typing using 1D or 2D data analysis technique respectively. 1 Blind represents the scenario that the whole prostate gland is dose escalated. 2 UTT_1D and UTT_2D represent ultrasound tissue typing using 1D or 2D data analysis technique respectively.

Treatment of metastatic tumors of the choroid with proton beam irradiation

To describe the clinical outcomes of patients treated by proton beam irradiation for choroidal metastatic tumors. Noncomparative case series. A retrospective chart review was performed on a series of 63 patients (76 eyes) with choroidal metastases treated with proton beam therapy between December 1989 and September 2000. Patients were treated with 2 fractions of 14 cobalt gray equivalents (CGEs) (CGE = proton Gy x relative biological effectiveness 1.1), each using a nonoperative "light-field" technique. Ophthalmologic follow-up was available for 46 patients (55 eyes), with a mean follow-up time of 10 months. The medical record or the Social Security Death Index was used to obtain survival status, which was available in 94% of cases. Tumor regression, recurrence, treatment-associated complications, and visual acuity were evaluated by ophthalmologic examination and ultrasonography. Eye retention and length of survival also were assessed. At the time of ocular diagnosis, 49 patients reported a history of a primary cancer. Median survival time after ocular diagnosis was 16 months through May 2003. Most choroidal metastases were dome shaped (62%) and located at the posterior pole (95%). Mean tumor height was approximately 3.5 mm, and serous retinal detachment was seen in 63% of cases. Eighty-four percent of treated tumors regressed completely within 5 months of treatment, and none of these recurred. Retinal detachment resolved in 82% of patients within 3.8 months after treatment, and visual acuity was preserved or improved in 47% of the patients. Complications occurred in 56% of cases and included madarosis, keratitis, dry eye syndrome, cataract, neovascular glaucoma, chorioretinal atrophy, radiation papillopathy, and radiation maculopathy. None of the treated eyes required enucleation. Proton beam irradiation is a useful therapeutic approach for choroidal metastases; it allows retention of the globe, achieves a high probability of local tumor control, and helps to avoid pain and visual loss. Although complications occur in most cases, many of these are minor and are not associated with a change in function. This modality is accurate and efficient, because it only entails 2 treatment fractions and does not require surgery for tumor localization.

Zukünftige technische Fortschritte in der Radio-Onkologie

PurposeTo review the current limits on the efficacy of radiotherapy (RT) due to technical factors and to assess the potential for major improvements in technology. Methods and MaterialsThe method of this review was to assess the efficacy of current RT in general terms; strategies for improving RT; historical record of technological advances; rationale for further reductions of treatment volume; and importance of defining and excluding nontarget tissues from the target volume. The basis for the interest in proton beam RT is developed, and the relative dose distributions of intensity-modulated radiotherapy (IMRT) and intensity-modulated proton RT (IMPT) are discussed. The discovery of the proton and the first proposal that protons be used in RT is described. This is followed by a brief mention of the clinical outcome studies of proton RT. Likely technical advances to be integrated into advanced proton RT are considered, specifically, four-dimensional treatment planning and delivery. Finally, the increment in cost of some of these developments is presented. ResultsFor definitive RT, dose limits are set by the tolerance of normal tissues/structures adjacent or near to the target. Using imaging fusion of CT, MRI, positron emission tomography, magnetic resonance spectroscopic imaging, and other studies will result in improved definition of the target margins. Proton beams are likely to replace photon beams because of their physical characteristics. Namely, for each beam path, the dose deep to the target is zero, across the target it is uniform, and proximal to the target it is less. Proton therapy can use as many beams, beam angles, noncoplanar, and dynamic, as well as static, intensity modulation, as can photon plans. The ability for much greater accuracy in defining the target position in space and then maintaining the target in a constant position in the radiation beam despite target movement between and during dose fractions will be possible. The cost of proton RT will be modestly higher than comparable high technology photon therapy. ConclusionThe technology of RT is clearly experiencing intense and rapid technical developments as pertains to treatment planning and dose delivery. It is predicted that radical dose RT will move to proton beam technology and that the treatment will be four dimensional (the fourth dimension is time). The impact will be higher tumor control probability and reduced frequency and severity of treatment-related morbidity.

Enhancing the efficacy of radiation therapy by incorporating spatial distribution of heterogeneous biology

It is well known that the distribution of clonogen (or functional units), radiosensitivity, and cell proliferation rate in most tumors and sensitive structures are heterogeneous. Recent progress in biological imaging is making the mapping of spatial biology distribution increasingly possible. To optimize efficacy of radiotherapy and in particularly intensity modulated radiation therapy (IMRT), it is desirable to take the biological information into account and to produce customized non-uniform dose distributions on a patient specific basis. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data derived from biological images into IMRT inverse optimization and to show its advantage in enhancing the tumor control probability (TCP) and reducing the normal tissue complication probability (NTCP). A linear quadratic (LQ) model was used as a starting point of the study. According to the LQ model, the status of the tumor at a spatial point was characterized by clonogen density (?), radiosensitivity (?), and proliferation rate (?). For sensitive organs, the functional unit density was employed to describe the functional importance at a point within the given structure. We hypothesize that the biological model parameter distributions can be derived from the biological imaging data (to give a few examples, clonogen density in malignant glioma can be obtained based the choline/creatine ratio by using MR spectroscopic imaging, radiosensitivity depends on the local oxygen level, the tumor proliferation rate is proportional to the voxel activity level in the case of DNA proliferation imaging (e.g., FLT-PET), and functional importance distribution can be obtained by perfusion imaging). The desired spatial variation form of the radiation dose (or prescription dose distribution) depends on (?, ?, ?) distributions and is determined by maximizing the TCP under the constraint of constant integral tumor dose. Using the above definition and the LQ model, we deduced a general formula that allows us to prescribe dose to each tumor voxel in an automatic fashion. An objective function with the voxel-dependent prescription described above was then constructed. A group of voxel-dependent important factors were also introduced to consider the functional unit density distribution in sensitive structures. A conjugate-gradient algorithm was implemented for the optimization of the objective function. A brain tumor case and a prostate case with biology information derived from functional imaging were used to test the new inverse planning system. For comparison, conventional IMRT plans with uniform dose prescription were also generated for these two cases. The biological indices, TCP and NTCP, were used to evaluate the proposed technique and to show its superiority over the conventional planning scheme. An IMRT inverse planning framework has been established for dealing with spatially heterogeneous biology distribution. The influence of the model parameters, ?, ?, and ?, on the final plans were studied and the study seems to indicate that the ? and ? play more important role in comparison to the tumor cell density. Our study also demonstrated that it is technically feasible to produce deliberately non-uniform dose distributions with consideration of biological information. The biological model established in this study was found to be useful for determining the prescription dose distribution. Compared with the conventional inverse planning scheme, the new system was capable of generating IMRT plans with much higher TCPs while keeping the NTCPs at their conventional levels. Incorporating patient-specific biological information into IMRT inverse optimization provides a significant opportunity to truly individualize radiation treatment. It allows us to utilize maximally the technical capacity of IMRT and provides us with much improved means for safe and intelligent dose escalation.

The Gray Lecture 2001: coming technical advances in radiation oncology

Purpose: To review the current limits on the efficacy of radiotherapy (RT) due to technical factors and to assess the potential for major improvements in technology.Methods and Materials: The method of this review was to assess the efficacy of current RT in general terms; strategies for improving RT; historical record of technological advances; rationale for further reductions of treatment volume; and importance of defining and excluding nontarget tissues from the target volume. The basis for the interest in proton beam RT is developed, and the relative dose distributions of intensity-modulated radiotherapy (IMRT) and intensity-modulated proton RT (IMPT) are discussed. The discovery of the proton and the first proposal that protons be used in RT is described. This is followed by a brief mention of the clinical outcome studies of proton RT. Likely technical advances to be integrated into advanced proton RT are considered, specifically, four-dimensional treatment planning and delivery. Finally, the increment in cost of some of these developments is presented.Results: For definitive RT, dose limits are set by the tolerance of normal tissues/structures adjacent or near to the target. Using imaging fusion of CT, MRI, positron emission tomography, magnetic resonance spectroscopic imaging, and other studies will result in improved definition of the target margins. Proton beams are likely to replace photon beams because of their physical characteristics. Namely, for each beam path, the dose deep to the target is zero, across the target it is uniform, and proximal to the target it is less. Proton therapy can use as many beams, beam angles, noncoplanar, and dynamic, as well as static, intensity modulation, as can photon plans. The ability for much greater accuracy in defining the target position in space and then maintaining the target in a constant position in the radiation beam despite target movement between and during dose fractions will be possible. The cost of proton RT will be modestly higher than comparable high technology photon therapy.Conclusion: The technology of RT is clearly experiencing intense and rapid technical developments as pertains to treatment planning and dose delivery. It is predicted that radical dose RT will move to proton beam technology and that the treatment will be four dimensional (the fourth dimension is time). The impact will be higher tumor control probability and reduced frequency and severity of treatment-related morbidity.

Definitive radiotherapy in the management of chemodectomas arising in the temporal bone, carotid body, and glomus vagale.

To evaluate the results of treatment for 71 patients with 80 chemodectomas of the temporal bone, carotid body, or glomus vagale who were treated with radiation therapy (RT) alone (72 tumors in 71 patients) or subtotal resection and RT (8 tumors) at the University of Florida between 1968 and 1998. Sixty-six lesions were previously untreated, whereas 14 had undergone prior treatment (surgery, 11 lesions; RT, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All three patients who received prior RT had been treated at other institutions. Patients had minimum follow-up times as follows: 2 years, 66 patients (93%); 5 years, 53 patients (75%); 10 years, 37 patients (52%); 15 years, 29 patients (41%); 20 years, 18 patients (25%); 25 years, 12 patients (17%); and 30 years, 4 patients (6%). There were five local recurrences at 2.6 years, 4.6 years, 5.3 years, 8.3 years, and 18.8 years, respectively. Four were in glomus jugulare tumors and one was a carotid body tumor. Two of the four patients with glomus jugulare failures were salvaged, one with stereotactic radiosurgery and one with surgery and postoperative RT at another institution. Two of the five recurrences had been treated previously at other institutions with RT and/or surgery. Treatment for a third recurrence was discontinued, against medical advice, before receiving the prescribed dose. There were, therefore, only 2 failures in 65 previously untreated lesions receiving the prescribed course of RT. The overall crude local control rate for all 80 lesions was 94%, with an ultimate local control rate of 96% after salvage treatment. The incidence of treatment-related complications was low. Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone and neck. There were no severe treatment complications.

Application of constrained optimization to radiotherapy planning.

Essential for the calculation of photon fluence distributions for intensity modulated radiotherapy (IMRT) is the use of a suitable objective function. The objective function should reflect the clinical aims of tumor control and low side effect probability. Individual radiobiological parameters for patient organs are not yet available with sufficient accuracy. Some of the major drawbacks of some current optimization methods include an inability to converge to a solution for arbitrary input parameters, and/or a need for intensive user input in order to guide the optimization. In this work, a constrained optimization method was implemented and tested. It is closely related to the demanded clinical aims, avoiding the drawbacks mentioned above. In a prototype treatment planning system for IMRT, tumor control was guaranteed by setting a lower boundary for target dose. The aim of low complication is fulfilled by minimizing the dose to organs at risk. If only one type of tissue is involved, there is no absolute need for radiobiological parameters. For different organs, threshold dose, relative seriality of the organs or an upper dose limit could be set. All parameters, however, were optional, and could be omitted. Dose-volume constraints were not used, avoiding the possibility of local minima in the objective function. The approach was benchmarked through the simulation of both a head and neck and a lung case. A cylinder phantom with precalculated dose distributions of individual pencil beams was used. The dose to regions at risk could be significantly reduced using at least seven ports of beam incidence. Increasing the number of ports beyond seven produced only minor further gain. The relative seriality of organs was modeled through the use of an added exponent to the dose. This approach however increased calculation time significantly. The alternative of setting an upper limit is much faster and allows direct control of the maximum dose. Constrained optimization guarantees high tumor control probability, it is computationally more efficient than adding penalty terms to the objective function, and the input parameters are dose limits known in clinical practice.

Radiotherapy in the management of chemodectomas of the carotid body and glomus vagale

Because only limited data are available pertaining to radiotherapy for chemodectomas of the carotid body and glomus vagale, we reviewed our experience. Fifteen patients with 23 chemodectomas of either the carotid body or glomus vagale were treated with radiotherapy at the University of Florida between 1981 and 1995. Eighteen lesions were previously untreated. One patient had received prior radiotherapy at another institution and four patients had received prior surgery. The local control rate at 10 years, calculated by the Kaplan-Meier product-limit method, was 96% for the overall group of 23 lesions and 100% for the subset of 22 lesions without prior radiotherapy. The 10-year cause-specific survival rate was 89% for all 15 patients and 100% for the 14 patients who had received no prior radiotherapy. No patient experienced a significant complication secondary to irradiation. Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the carotid body and glomus vagale.

A little to a lot or a lot to a little: is NTCP always minimized in multiport therapy?

Purpose: We address the question of whether or not, for the same average (or integral) dose, a smaller uniform dose to an entire normal tissue structure always results in a lower normal tissue complication probability (NTCP) than does a proportionally larger dose to a partial volume of the same structure. Methods and Materials: A recent compilation of NTCP data and two theoretical formulations of the dependence of NTCP on dose and partial volume irradiated—the Lyman probit equation and the binomial model—are used to examine this question. Both models fit equally well available NTCP data. Results: Empirical data indicate that for lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating a partial volume fraction rather than the entire normal organ. The binomial model supports this interpretation, whereas the probit model predicts that for all organs uniform irradiation of the whole organ always results in the lowest possible NTCP. Conclusions: In contrast to what is commonly believed, this study suggests that for at least two normal tissues, namely lung and kidney, there may be situations where “a lot to a little” (i.e., fewer treatment ports) will result in higher tumor control probability and better treatment plan than “a little to a lot” (i.e., multifield treatment). This finding, which is independent of the binomial or probit models used here, depends only on the accuracy of the empirical NTCP data. It is also interesting to note that: a) lung and kidney are commonly classified as parallel tissues, while the others have more of a serial architecture; and b) the choice of the NTCP model can have a profound impact on treatment planning decisions.

Radiotherapy in the Management of Temporal Bone Chemodectoma

Forty patients with 42 temporal bone chemodectomas were treated with radiotherapy alone (37 tumors) or subtotal resection and irradiation (5 tumors) at the University of Florida between 1968 and 1992. Thirty-three lesions were previously untreated, whereas 9 had undergone prior treatment (surgery, 6 lesions; radiotherapy, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All 3 patients who received prior radiotherapy had been treated at other institutions. Patients had minimum follow-up times as follows: 2 years, 40 patients (100%); 5 years, 31 patients (78%); 10 years, 21 patients (53%); 15 years, 16 patients (40%); 20 years, 9 patients (23%); and 25 years, 2 patients (5%). The local control rate at 20 years, calculated by the Kaplan-Meier product-limit method for the overall group of 42 lesions, was 89%. The likelihood of cause-specific survival at 20 years was 94%. The incidence of treatment-related complications was acceptable. We conclude that irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone.