Reirradiation with stereotactic body radiotherapy: analysis of human spinal cord tolerance using the generalized linear-quadratic model.

AIM: Using the generalized linear-quadratic (gLQ) model, we reanalyzed published dosimetric data from patients with radiation myelopathy (RM) after reirradiation with spinal stereotactic body radiotherapy (SBRT). MATERIALS & METHODS: Based on a published study, the thecal sac dose of five RM patients and 14 no RM patients were reanalyzed using gLQ model. Maximum point doses (Pmax) in the thecal sac were obtained. The gLQ-based biological effective doses were calculated and normalized (nBEDgLQ) to a 2-Gy equivalent dose (nBEDgLQ = Gy2/2_gLQ). The initial conventional radiotherapy dose, converted to Gy2/2_gLQ, was added. RESULTS: Total (conventional radiotherapy + SBRT) mean Pmax nBEDgLQ was lower in no RM than RM patients: 59.2 Gy2/2_gLQ (range: 37.5-101.9) versus 94.8 Gy2/2_gLQ (range: 70.2-133.4) (p = 0.0016). The proportion of total Pmax nBEDgLQ accounted for by the SBRT Pmax nBEDgLQ was higher for RM patients. No RMs were seen below a total spinal cord nBEDgLQ of 70 Gy2/2_gLQ. CONCLUSION: The gLQ-derived spinal cord tolerance for total nBEDgLQ was 70 Gy2/2_gLQ.

Onset time of tumor repopulation for cervical cancer: first evidence from clinical data.

PURPOSE: Accelerated tumor repopulation has significant implications in low-dose rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer, using clinical data. METHODS AND MATERIALS: The linear quadratic (LQ) model extended for tumor repopulation was used to analyze clinical data and magnetic resonance imaging-based three-dimensional tumor volumetric regression data from 80 cervical cancer patients who received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. Patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least χ(2) method was used to fit the TCP data with two free parameters: onset time (T(k)) of accelerated repopulation and number of clonogens (K), while other LQ model parameters were adopted from the literature, due to the limited patient data. RESULTS: Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated with higher TCP. Using the LQ model, we achieved the best fit with onset time T(k) of 19 days and K of 139, with uncertainty ranges of (11, 22) days for T(k) and (48, 1822) for K, respectively. CONCLUSION: This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from clinical data by using the LQ model. Our study verifies the fact that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.

Direct sagittal image registration and tumor delineation on sagittal magnetic resonance imaging sequences for image-guided brachytherapy of cervical cancer.

AIM: To test and evaluate direct sagittal-plane tumor delineation for MRI-based image-guided brachytherapy (IGBT) planning for patients with cervical cancer. MATERIALS AND METHODS: An image registration method based on the sagittal source MR images was developed and employed in ten patients with an indwelling ring/tandem applicator. The gross tumor volume (GTV) was delineated separately on the sagittal (GTV-S) and axial images (GTV-A). GTV conformity indices and dose-volume histogram analyses were compared among GTV-S and GTV-A (paired t-test). RESULTS: Image quality and delineation in the sagittal images was graded superior to the axial images. The ratio of common volume of the axial and sagittal volumes to that of the axial volume was 0.77 +/- (standard deviation) 0.2. The GTV-S mean volume (19.6 +/- 13.8 mL) was significantly larger than the GTV-A mean volume (10.3 +/- 7.3 mL, p=0.003). The GTV-S mean D99 (5.2 +/- 2.5 Gy) was significantly lower than the GTV-A mean D99 (6.9 +/- 2.7 Gy, p=0.013). The GTV-S mean D90 (6.8 +/- 2.8 Gy) was significantly lower than the GTV-A mean D90 (8.5 +/- 3.1 Gy, p=0.016). CONCLUSIONS: Registration of the sagittal source MRI and contouring the GTV directly on the sagittal images is feasible and practical for IGBT. Consistently larger sagittal GTVs may be explained by the better visualization and more continuous tumor topology in the sagittal plane, compared to the discrete oblique sectioning of the uterus/tumor and partial volume loss in the axial plane.

A generalized linear-quadratic model incorporating reciprocal time pattern of radiation damage repair.

PURPOSE: It has been conventionally assumed that the repair rate for sublethal damage (SLD) remains constant during the entire radiation course. However, increasing evidence from animal studies suggest that this may not the case. Rather, it appears that the repair rate for radiation-induced SLD slows down with increasing time. Such a slowdown in repair would suggest that the exponential repair pattern would not necessarily accurately predict repair process. As a result, the purpose of this study was to investigate a new generalized linear-quadratic (LQ) model incorporating a repair pattern with reciprocal time. The new formulas were tested with published experimental data. METHODS: The LQ model has been widely used in radiation therapy, and the parameter G in the surviving fraction represents the repair process of sublethal damage with T(r) as the repair half-time. When a reciprocal pattern of repair process was adopted, a closed form of G was derived analytically for arbitrary radiation schemes. The published animal data adopted to test the reciprocal formulas. RESULTS: A generalized LQ model to describe the repair process in a reciprocal pattern was obtained. Subsequently, formulas for special cases were derived from this general form. The reciprocal model showed a better fit to the animal data than the exponential model, particularly for the ED50 data (reduced χ(2) (min) of 2.0 vs 4.3, p = 0.11 vs 0.006), with the following gLQ parameters: α/ß = 2.6-4.8 Gy, T(r) = 3.2-3.9 h for rat feet skin, and α/ß = 0.9 Gy, T(r) = 1.1 h for rat spinal cord. CONCLUSIONS: These results of repair process following a reciprocal time suggest that the generalized LQ model incorporating the reciprocal time of sublethal damage repair shows a better fit than the exponential repair model. These formulas can be used to analyze the experimental and clinical data, where a slowing-down repair process appears during the course of radiation therapy.

Characterizing tumor heterogeneity with functional imaging and quantifying high-risk tumor volume for early prediction of treatment outcome: cervical cancer as a model.

PURPOSE: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. METHODS AND MATERIALS: DCE-MRI was performed in 102 stage IB(2)-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). RESULTS: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm(3), respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 × 10(-8), 2.0 × 10(-8)) and disease-specific survival (p = 1.9 × 10(-4), 2.1 × 10(-6), 2.5 × 10(-7), respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. DISCUSSION: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2-5 weeks into treatment.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline.

PURPOSE: To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. METHODS AND MATERIALS: Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. RESULTS: The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. CONCLUSIONS: Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).

Characterizing at-Risk Voxels by Using Perfusion Magnetic Resonance Imaging for Cervical Cancer during Radiotherapy.

The number of voxels with low signal intensity (Low DCE voxels) might be potentially related to treatment failure, which might be associated with the tumor oxygenation status. Our goal was to investigate whether at-risk voxels can be used to predict treatment outcome during radiation therapy for cervical cancer. 80 patients with Stage IB2-IVB cervical cancer were included. Four sequential MRI scans were performed at pre-RT, every 2-2.5 weeks during RT, and post-radiotherapy. 3D volumetric data including tumor regression and tumor perfusion from dynamic contrast enhanced MRI (DCE-MRI) were analyzed. Based on the signal intensity (SI) curves of the DCE-MRI, the low-DCE tumor voxels was obtained for individual patients. The predictive power of low DCE voxels in predicting the treatment outcomes was evaluated by Kaplan-Meier survival analysis. Correlation of low DCE voxels with hemoglobin (Hgb) was checked by Pearson Correlation. The actuarial local control rate and survival rate in the patient group with a small number of low DCE voxels were 89.7% and 76.9%, compared with 75.6% and 51.2% in the patient group with a big number of low DCE voxels for the MRI study #1, and 94.1% and 80.4% compared with 62.1% and 34.5% for the MRI study #2, and 95.7% and 78.7% compared with 63.6% and 42.4% for the MRI study #3, respectively. Low DCE voxels were significantly correlated with Hgb. At-risk voxels can be used to predict the outcomes and help understand tumor heterogeneity of response to RT. The Hgb level and tumor perfusion during RT influence the radioresponsiveness and survival in cervical cancer patients.

Imaging changes after stereotactic body radiation therapy for lung and liver tumors.

Stereotactic body radiation therapy (SBRT) is gaining wide acceptance as a treatment modality for lung and liver tumors, and it is crucial to make an accurate evaluation of the local effects of ablative doses of radiation in terms of local tumor control and normal tissue reaction or damage. The very complex radiation dose distribution of SBRT, the use of a large number of non-opposing and noncoplanar beams, and the delivery of individual ablative doses of radiation may cause substantially different radiographic appearance on diagnostic imaging compared with conventional radiation therapy. Different patterns of radiographic changes have been observed in the lung and liver after SBRT. This article reviews the post-SBRT imaging changes in the lung and liver. Since computed tomography and PET are the most commonly used diagnostic imaging tools for monitoring lung tumor and computed tomography for liver tumors, this article will focus on the changes observed on those imaging modalities.

Stereotactic radiosurgery alone for patients with 1-4 radioresistant brain metastases.

Brain metastases from radioresistant histologies are perceived to be less responsive to WBRT compared to other histologies, and stereotactic radiosurgery (SRS) may provide better local control. The aim of this study was to examine the outcomes of patients with 1-4 brain metastasis from radioresistant histologies (renal cell carcinoma and melanoma) treated with SRS alone. Thirty-eight patients with 1-4 radioresistant brain metastases (66 lesions) were treated with SRS alone. The median age was 55 years. Fourteen and 24 patients had renal cell carcinoma (RCC) and melanoma brain metastases, respectively. Distribution of number of lesions was as follows: one lesion, 22 patients; 2 lesions, 8 patients; 3 lesions, 5 patients; and 4 lesions, 3 patients. Distribution of RTOG recursive partitioning analysis (RPA) classes was as follows: II, 37 patients and III, 1 patient. The median marginal dose was 20 Gy. The median follow-up was 6.1 months. The 3-, 6-, 9-, 12-, and 18-month local control (LC) rates were 87.9, 81.4, 67.9, 67.9, and 60.3%, respectively. The corresponding free-from-distant-brain failure (FFDBF) rates were 71.3, 58.1, 49.8, 40.2, and 27.6%. The corresponding progression-free survival (PFS) rates were 55.3, 41.9, 33, 23.3, and 13.3%. RCC histology was associated with better LC (P = 0.0055). Although SRS alone could yield reasonable LC in patients with 1-4 radioresistant brain metastases, the risk of distant brain failure was substantial. The approach of routine omission of WBRT outside of a trial setting should be used judiciously.

Stereotactic body radiation therapy for oligometastases.

There are data in the literature to suggest the presence of an oligometastatic state, and local aggressive therapy of the oligometastases may improve outcomes including survival. Stereotactic body radiation therapy has emerged as one of the local therapy options for oligometastases in various body sites, most commonly in the lung and the liver. Retrospective studies and clinical trials have demonstrated promising results with the use of stereotactic body radiation therapy for oligometastases. However, most of the studies have relatively short follow-up intervals. Longer follow-up is necessary to better define the role of stereotactic body radiation therapy in the management of patients with oligometastases. Given the high propensity for distant progression, the combination of novel systemic therapy and stereotactic body radiation therapy is to be explored.

When tumor repopulation starts? The onset time of prostate cancer during radiation therapy.

PURPOSE: To analyze published clinical data and provide a preliminary estimate of tumor repopulation rate and its onset time during radiation therapy for prostate cancer. METHODS: Data on prostate cancer treated with external beam radiotherapy (EBRT) by Perez et al. (2004), Amdur et al. (1990) and Lai et al. (1991) were analyzed in this study. The stage-combined pelvic control rate from Perez et al. was calculated to be 0.95±0.01, 0.87±0.02, and 0.72±0.04 for patients treated ≤7 weeks, 7.1-9 weeks, and >9 weeks respectively. Based on the Linear-Quadratic model, extended to account for tumor repopulation, the least χ² method was used to fit the clinical data and derive the onset time (T(k)) and effective doubling time (T(d)) for prostate cancer. Similar analysis was performed for the other two datasets. RESULTS: Best fit was achieved with onset time T(k)=34±7 days and doubling time T(d)=12±2 days. These parameters were independent of the choice of the α/ß values currently published in the literature. Analyses of the other two datasets showed T(k)=42±7 days with T(d)=9 ± 3 days, and T(k)=34±6 days with T(d)=34±5 days, respectively. T(k) was found to be dependent on tumor stage. CONCLUSIONS: Consistent values for onset time T(k) were obtained from different datasets, while the range of doubling time T(d) was large. Tumor repopulation starts no later than 58 days (at 90% confidence level) in the course of EBRT for prostate cancer.

Sequential magnetic resonance imaging of cervical cancer: the predictive value of absolute tumor volume and regression ratio measured before, during, and after radiation therapy.

BACKGROUND: The objectives of this study were to investigate outcome prediction by measuring absolute tumor volume and regression ratios using serial magnetic resonance imaging (MRI) during radiation therapy (RT) for cervical cancer and to develop algorithms capable of identifying patients at risk of a poor therapeutic outcome. METHODS: Eighty patients with stage IB2 through IVA cervical cancer underwent 4 MRI scans: before RT (MRI1), during RT at 2 to 2.5 weeks (MRI2) at 4 to 5 weeks (MRI3), and 1 to 2 months after RT (MRI4). The median follow-up was 6.2 years (range, 0.2-9.4 years). Tumor volumes at MRI1, MRI2, MRI3, and MRI4 (V1, V2, V3, and V4, respectively) and tumor regression ratios (V2/V1, V3/V1, and V4/V1) were measured by 3-dimensional volumetry. Predictive metrics based on tumor volume/regression parameters were correlated with ultimate clinical outcomes, including tumor local recurrence (LR) and dying of disease (DOD). Predictive power was evaluated using the Mann-Whitney test, sensitivity/specificity analyses, and Kaplan-Meier analyses. RESULTS: Both tumor volume and regression ratio were strongly correlated with LR (P=.06, P = 5×10(-4), P=1×10(-6), and P=2×10(-8) for V1, V2, V3, and V4, respectively; and P=7×10(-5), P=1×10(-6), and P=1×10(-8) for V2/V1, V3/V1, and V4/V1, respectively) and DOD (P=.015, P=.004, P=.001, and P=3×10(-4) for V1, V2, V3, and V4, respectively; and P=.03, P=.009, and P=3×10(-4) for V2/V1, V3/V1, and V4/V1, respectively). Algorithms that combined tumor volumes and regression ratios improved predictive power (sensitivity, 61%-89%; specificity, 79%-100%). The strongest predictor, pre-RT volume and regression ratio at MRI3 (V1>40 cm3 and V3/V1>20%, respectively), achieved 89% sensitivity, 87% specificity, and 88% accuracy for LR and achieved 54% sensitivity, 83% specificity, and 73% accuracy for DOD. CONCLUSIONS: The current results suggested that tumor volume/regression parameters obtained during primary therapy are useful in predicting LR and DOD. Both tumor volume and regression ratio provided important information as early outcome predictors that may guide early intervention for patients with cervical cancer who are at high risk of treatment failure.

A generalized linear-quadratic model for radiosurgery, stereotactic body radiation therapy, and high-dose rate brachytherapy.

Conventional radiation therapy for cancer usually consists of multiple treatments (called fractions) with low doses of radiation. These dose schemes are planned with the guidance of the linear-quadratic (LQ) model, which has been the most prevalent model for designing dose schemes in radiation therapy. The high-dose fractions used in newer advanced radiosurgery, stereotactic radiation therapy, and high-dose rate brachytherapy techniques, however, cannot be accurately calculated with the traditional LQ model. To address this problem, we developed a generalized LQ (gLQ) model that encompasses the entire range of possible dose delivery patterns and derived formulas for special radiotherapy schemes. We show that the gLQ model can naturally derive the traditional LQ model for low-dose and low-dose rate irradiation and the target model for high-dose irradiation as two special cases of gLQ. LQ and gLQ models were compared with published data obtained in vitro from Chinese hamster ovary cells across a wide dose range [0 to approximately 11.5 gray (Gy)] and from animals with dose fractions up to 13.5 Gy. The gLQ model provided consistent interpretation across the full dose range, whereas the LQ model generated parameters that depended on dose range, fitted only data with doses of 3.25 Gy or less, and failed to predict high-dose responses. Therefore, the gLQ model is useful for analyzing experimental radiation response data across wide dose ranges and translating common low-dose clinical experience into high-dose radiotherapy schemes for advanced radiation treatments.

Stereotactic body radiation therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adults and it is frequently associated with cirrhosis. Surgical resection or orthotopic liver transplantation can be curative but only 30-40% of patients may benefit from curative radical treatment. Stereotactic body radiation therapy (SBRT) has emerged as a promising non-invasive therapy for patients with unresectable HCC and it may potentially serve as a bridging therapy for patients awaiting transplantation. There are a limited number of clinical trials examining the use of SBRT in patients with HCC and very good local tumor control and acceptable toxicities have been reported. This article provides an overview on the use of SBRT in the management of HCC.

Stereotactic body radiation therapy (stereotactic ablative radiotherapy) for stage I non-small cell lung cancer--updates of radiobiology, techniques, and clinical outcomes.

Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), has emerged as one of the standard treatment options for stage I non-small cell lung cancer (NSCLC), mainly in medically inoperable patients. Its use has also been explored in operable patients. A large body of experience, either from retrospective studies or clinical trials, has been accumulated over the years and more is known about the radiobiology, cancer biology, technical aspects, clinical outcomes, and toxicities of SBRT. This article provides updates of these aspects of SBRT for stage I NSCLC.

Management of metastatic spinal cord compression.

Spinal cord compression (SCC) from spinal metastasis is a common complication in cancer and if left untreated, permanent paraplegia or quadriplegia will occur. Timely diagnosis is crucial in preventing permanent neurologic damage. Once SCC is suspected, diagnostic imaging of the spine should be obtained to confirm diagnosis. Treatment consists of surgery, radiotherapy or a combination of both. Stereotactic body radiotherapy has also been incorporated into the management of SCC. The treatment decision should be made based on multiple factors, including tumor histology, retropulsion of bony fragments, performance status of the patient and status of extraspinal systemic disease. This review focuses on the pathophysiology, diagnosis and management of SCC.

Stereotactic body radiation therapy for spinal metastases.

Stereotactic body radiation therapy (SBRT) has emerged as a novel treatment modality for spinal metastases. Due to advances in radiation delivery technologies, it is now possible to deliver ablative doses to spinal metastases safely and effectively, and in particular high-dose re-irradiation. Data from the literature has demonstrated high rates of pain and local control with SBRT for spinal metastases, which is an active area of clinical investigation. Although there are potential therapeutic gains with spine SBRT, toxicities rarely seen with conventional radiotherapy, such as radiation-induced myelopathy and vertebral fractures, have been observed after SBRT in a small percentage of patients. Prospective clinical trials are required to define the role of SBRT in the management of spinal metastasis and to determine the appropriateness of using SBRT in various clinical settings. The purpose of this review is to provide an overview of the current state of spine SBRT practice.

Ultra-early predictive assay for treatment failure using functional magnetic resonance imaging and clinical prognostic parameters in cervical cancer.

BACKGROUND: The authors prospectively evaluated magnetic resonance imaging (MRI) parameters quantifying heterogeneous perfusion pattern and residual tumor volume early during treatment in cervical cancer, and compared their predictive power for primary tumor recurrence and cancer death with the standard clinical prognostic factors. A novel approach of augmenting the predictive power of clinical prognostic factors with MRI parameters was assessed. METHODS: Sixty-two cervical cancer patients underwent dynamic contrast-enhanced (DCE) MRI before and during early radiation/chemotherapy (2-2.5 weeks into treatment). Heterogeneous tumor perfusion was analyzed by signal intensity (SI) of each tumor voxel. Poorly perfused tumor regions were quantified as lower 10th percentile of SI (SI[10%]). DCE-MRI and 3-dimensional (3D) tumor volumetry MRI parameters were assessed as predictors of recurrence and cancer death (median follow-up, 4.1 years). Their discriminating capacity was compared with clinical prognostic factors (stage, lymph node status, histology) using sensitivity/specificity and Cox regression analysis. RESULTS: SI(10%) and 3D volume 2-2.5 weeks into therapy independently predicted disease recurrence (hazard ratio [HR], 2.6; 95% confidence interval [95% CI], 1.0-6.5 [P = .04] and HR, 1.9; 95% CI, 1.1-3.5 [P = .03], respectively) and death (HR, 1.9; 95% CI, 1.0-3.5 [P = .03] and HR, 1.9; 95% CI, 1.2-2.9 [P = .01], respectively), and were superior to clinical prognostic factors. The addition of MRI parameters to clinical prognostic factors increased sensitivity and specificity of clinical prognostic factors from 71% and 51%, respectively, to 100% and 71%, respectively, for predicting recurrence, and from 79% and 54%, respectively, to 93% and 60%, respectively, for predicting death. CONCLUSIONS: MRI parameters reflecting heterogeneous tumor perfusion and subtle tumor volume change early during radiation/chemotherapy are independent and better predictors of tumor recurrence and death than clinical prognostic factors. The combination of clinical prognostic factors and MRI parameters further improves early prediction of treatment failure and may enable a window of opportunity to alter treatment strategy.

Predicting outcomes in cervical cancer: a kinetic model of tumor regression during radiation therapy.

Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P < 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S(2) < 0.70 vs. S(2) > or = 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time (T(1/2) < 22 days versus T(1/2) > or = 22 days, P < 0.001). The 6-year disease-specific survival was 73% versus 41% with S(2) < 0.70 versus S(2) > or = 0.70 (P = 0.025), and 87% vs. 52% with T(1/2) < 22 days versus T(1/2) > or = 22 days (P = 0.002). Our approach illustrates the promise of volume-based tumor response modeling to improve early outcome predictions that can be used to enable personalized adaptive therapy.