Impact of biochemical failure classification on clinical outcome: a secondary analysis of Radiation Therapy Oncology Group 9202 and 9413.

BACKGROUND: Biochemical failure (BF) after radiation therapy is defined on the basis of a rising prostate-specific antigen (PSA) level (A1 failure) or any event that prompts the initiation of salvage androgen-deprivation therapy without PSA failure (A2). It was hypothesized that A2 failure may have a different prognosis. METHODS: Data for 2799 eligible patients from Radiation Therapy Oncology Group (RTOG) 9202 and RTOG 9413 were analyzed. BF was defined according to the 1997 American Society for Therapeutic Radiology and Oncology consensus definition as A1 for PSA failure or as A2 for the start of salvage hormone therapy before 3 consecutive PSA rises. RESULTS: Rates of all-cause mortality (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-2.0; P < .0001) and distant metastasis (DM; HR, 1.6; 95% CI, 1.3-2.0; P < .0001) were greater with A2 failure. The 5-year overall survival (OS) rates were 88.2% and 74.6% for A1 and A2, respectively (P < .0001), and the DM rates were 15.7% and 29.0%, respectively (P < .0001). The DM rate was greater at 5 years for A2 patients with DM as the first sign of failure versus patients with other A2 failures (87.3% vs 11.7%, P < .001), and this also correlated with worse OS at 5 years: 81.1% for A2 failure without DM and 52.8% with DM (P < .001). After the removal of patients with DM, the difference between A1 and A2 BF persisted for OS (P = .002) but not for DM (P = .16) CONCLUSIONS: These results suggest that patients with rising PSA levels alone have less risk than those with A2 failures; although DM was the largest contributor of adverse risk to A2 failure, it did not account for all excess risk in A2 failure.

Prediction of liver function by using magnetic resonance-based portal venous perfusion imaging.

PURPOSE: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. METHODS AND MATERIALS: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. RESULTS: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. CONCLUSIONS: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which could aid in individualizing therapy, particularly for patients at risk for liver injury after RT.

Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer.

Introduction This phase II trial investigated chemoradiation followed by surgery and 2 years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60 mg/m(2) (days 1 and 22), paclitaxel 60 mg/m(2) (days 1, 8, 15, and 22), and 45 Gy hyperfractionated radiotherapy for 3 weeks followed by transhiatal esophagectomy. TM 20 mg PO QD was started 4 weeks post-op, and continued for 2 years to maintain the ceruloplasmin level between 5 and 15 mg/dl. Results Sixty-nine patients were enrolled (median age, 60 years). Sixty-six patients underwent surgery and 61 patients had a complete resection. Histologic complete response rate was 10 %. Twenty-one patients did not receive TM (metastases noted in the peri-operative period, prolonged post-operative recovery time, or patient refusal). Forty-eight patients started TM; 14 completed 24 months of treatment, 11 completed 10-18 months, 15 completed 2-8 months, and 8 completed ≤1 month. Twenty-seven patients had disease recurrence. With a median follow-up of 55 months, 25 patients were alive without disease, 1 was alive with disease, and 43 have died. Three-year recurrence-free survival was 44 % (95 % CI, 32-55 %) and the three-year overall survival was 45 % (95 % CI 33-56 %). Conclusions TM is an antiangiogenic agent that is well tolerated in the adjuvant setting. Disease-free survival and overall survival are promising when compared to historical controls treated at our institution with a similar regimen that did not include TM. However, the challenges associated with prolonged administration limit further investigation.

Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy.

BACKGROUND: Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. METHODS: Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3-5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. RESULTS: From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was -0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9-86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. CONCLUSIONS: Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.

Dosimetric analysis of radiation-induced gastric bleeding.

PURPOSE: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. METHODS AND MATERIALS: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of ≥grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. RESULTS: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD50 (normal) = 56 Gy and TD50 (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD50 value for the cirrhosis patients points out their greater sensitivity. CONCLUSIONS: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

A phase I clinical and pharmacology study using amifostine as a radioprotector in dose-escalated whole liver radiation therapy.

PURPOSE: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. METHODS AND MATERIALS: We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed. RESULTS: Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 ± 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 µM with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients. CONCLUSION: These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

Adaptive trial of personalized radiotherapy for intrahepatic cancer.

Primary liver cancer is a major health problem worldwide, with more than 500,000 new cases diagnosed yearly. Preliminary results suggest excellent local control rates of intrahepatic malignancies treated with stereotactic body radiation therapy (SBRT), but some patients have experienced life-threatening toxicity because the current approaches cannot accurately estimate residual liver function after treatment. An early-phase trial of SBRT in hepatocellular carcinoma patients, including those with compromised liver function, is described. Patients are treated with three fractions of SBRT, then treatment is paused for 4 weeks and liver function is evaluated by means of an indocyanine green assay. The size of the final two fractions of SBRT is determined based on the patient's indocyanine green assay after the first three fractions, so that the therapy is personalized to each patient's sensitivity to radiation. The sensitivity to the liver of the final two fractions of SBRT, compared with the first three fractions, is re-estimated using a Bayesian model throughout the trial, so this is an adaptive trial. The operating characteristics of the trial are described by Monte Carlo simulations.

Radiation dose-volume effects in the stomach and small bowel.

Published data suggest that the risk of moderately severe (>or=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely related to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.

Radiation-associated kidney injury.

The kidneys are the dose-limiting organs for radiotherapy to upper abdominal cancers and during total body irradiation. The incidence of radiotherapy-associated kidney injury is likely underreported owing to its long latency and because the toxicity is often attributed to more common causes of kidney injury. The pathophysiology of radiation injury is poorly understood. Its presentation can be acute and irreversible or subtle, with a gradual progressive dysfunction over years. A variety of dose and volume parameters have been associated with renal toxicity and are reviewed to provide treatment guidelines. The available predictive models are suboptimal and require validation. Mitigation of radiation nephropathy with angiotensin-converting enzyme inhibitors and other compounds has been shown in animal models and, more recently, in patients.

Radiation therapy and hearing loss.

A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associated ototoxicity as well as a detailed approach for scoring toxicity is presented.

Radiation-associated liver injury.

The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

Intra and interfraction mediastinal nodal region motion: implications for internal target volume expansions.

The purpose of this study was to determine the intra and interfraction motion of mediastinal lymph node regions. Ten patients with nonsmall-cell lung cancer underwent controlled inhale and exhale computed tomography (CT) scans during two sessions (40 total datasets) and mediastinal nodal stations 1-8 were outlined. Corresponding CT scans from different sessions were registered to remove setup error and, in this reference frame, the centroid of each nodal station was compared for right-left (RL), anterior-posterior (AP), and superior-inferior (SI) displacement. In addition, an anisotropic volume expansion encompassing the change of the nodal region margins in all directions was used. Intrafraction displacement was determined by comparing same session inhale-exhale scans. Interfraction reproducibility of nodal regions was determined by comparing the same respiratory phase scans between two sessions. Intrafraction displacement of centroid varied between nodal stations. All nodal regions moved posteriorly and superiorly with exhalation, and inferior nodal stations showed the most motion. Based on anisotropic expansion, nodal regions expanded mostly in the RL direction from inhale to exhale. The interpatient variations in intrafraction displacement were large compared with the displacements themselves. Moreover, there was substantial interfractional displacement ( approximately 5 mm). Mediastinal lymph node regions clearly move during breathing. In addition, deformation of nodal regions between inhale and exhale occurs. The degree of motion and deformation varies by station and by individual. This study indicates the potential advantage of characterizing individualized nodal region motion to safely maximize conformality of mediastinal nodal targets.

Determining if pretreatment PSA doubling time predicts PSA trajectories after radiation therapy for localized prostate cancer.

INTRODUCTION: To determine if pretreatment PSA doubling time (PSA-DT) can predict post-radiation therapy (RT) PSA trajectories for localized prostate cancer. MATERIALS AND METHODS: Three hundred and seventy-five prostate cancer patients treated with external beam RT without androgen deprivation therapy (ADT) were identified with an adequate number of PSA values. We utilized a linear mixed model (LMM) analysis to model longitudinal PSA data sets after definitive treatment. Post-treatment PSA trajectories were allowed to depend on the pre-RT PSA-DT, pre-RT PSA (iPSA), Gleason score (GS), and T-stage. RESULTS: Pre-RT PSA-DT had a borderline impact on predicting the rate of PSA rise after nadir (p=0.08). For a typical low risk patient (T1, GS6, iPSA 10), the predicted PSA-DT post-nadir was 21% shorter for pre-RT PSA-DT<24month compared to pre-RT PSA-DT>24month (19month vs. 24month). Additional significant predictors of post-RT PSA rate of rise included GS (p<0.0001), iPSA (p<0.0001), and T-stage (p=0.02). CONCLUSIONS: We observed a trend between rapidly rising pre-RT PSA and the post-RT post-nadir PSA rise. This effect appeared to be independent of iPSA, GS, or T-stage. The results presented suggest that pretreatment PSA-DT may help predict post-RT PSA trajectories.

Predicting biochemical failure and overall survival through intratherapy PSA changes during definitive external beam radiotherapy.

PURPOSE: To determine whether intratherapy prostate-specific antigen (itPSA) changes during radiotherapy (RT) predict prostate cancer outcomes. METHODS AND MATERIALS: We retrospectively identified patients treated with definitive external beam RT without hormonal therapy who had at least two itPSA measurements. We calculated the adjusted ratio of rise (ARR) in itPSA relative to the pretreatment baseline PSA for each patient. This was defined as ln(maximal itPSA + 1)/ln(baseline PSA + 1). We stratified patients according to an ARR of <1 vs. >1.1. This corresponded to an approximately <30% vs. >30% increase in PSA during RT. Univariate and multivariate analyses were performed examining for biochemical failure-free survival (BFFS) and overall survival (OS). RESULTS: At a median follow-up of 74 months, we identified 307 patients who met our criteria. Univariate analysis revealed that patients with an ARR of <1.1 (n = 182) had statistically significant inferior BFFS and OS compared with those with an ARR of >1.1 (n = 125). The median BFFS and OS for these two groups was 51 vs. 101 months (p = 0.001) and 96 vs. 128 months (p = 0.01), respectively. On multivariate analysis, the effect of ARR on the risk of biochemical failure for patients with an ARR of <1.1 was significant (p = 0.03) only during the first year after RT. In contrast, the effect of the ARR on OS remained significant for a full 5 years (p = 0.05). CONCLUSION: The results of our study have shown that an ARR of <1.1 predicts for inferior BFFS and OS in patients treated with RT alone. PSA measurement during RT is a novel clinical tool that could be used to identify patients who might warrant more aggressive therapeutic intervention.

In patients experiencing biochemical failure after radiotherapy, pretreatment risk group and PSA velocity predict differences in overall survival and biochemical failure-free interval.

PURPOSE: To characterize the demographics and survival outcomes of localized prostate cancer patients who developed biochemical failure (BF) according to a prostate-specific antigen (PSA) nadir plus 2 ng/mL. METHODS AND MATERIALS: We identified 375 prostate cancer patients who had undergone external beam radiotherapy without androgen deprivation therapy but with sufficient PSA data to study PSA kinetics. Of these patients, we identified 82 with BF. The pretreatment PSA velocity was calculated for each patient. RESULTS: For the BF cohort, 26% were low-risk and 74% were intermediate- or high-risk patients. Of the 82 BF patients, 16 (20%) were noted to have both low-risk disease and a pretreatment low PSA velocity of < or =2 ng/mL/y (termed "low-risk low-velocity" [LRLV]). The remaining BF patients had either intermediate- or high-risk features or a high PSA velocity >2 ng/mL/y (termed "higher risk" [HR]). For patients who had BF, the LRLV group had a delayed median time to BF of 55 months compared with 33 months for the HR patients (p = 0.04). With a median clinical follow-up of 112 months, the 5-year overall survival rate was 100% for the LRLV BF patients vs. 84% for the HR patients (p = 0.02). CONCLUSIONS: We observed that LRLV BF patients represent a sizeable proportion of all patients with treatment failure. However, when comparing LRLV BF with HR BF patients, the former had significantly better overall survival and a longer interval to BF. This suggests that not all BF events are equivalent and emphasizes the challenges associated with using BF alone as a surrogate for a survival endpoint.

Impact of common iliac nodal treatment on radiation outcomes in localized prostate cancer.

OBJECTIVES: The Radiation Therapy Oncology Group 9413 trial has shown an improvement in progression-free survival (PFS) with external beam radiotherapy that included the pelvic nodes. In clinical practice, two pelvic field size designs are in use. We examined the effect of differences in the level of pelvic nodal coverage using three-dimensional conformal radiotherapy on biochemical failure-free survival (BFFS) and PFS in early-stage prostate cancer. METHODS: The patients were identified retrospectively who had undergone whole pelvis (WP) or minipelvis (MP) three-dimensional conformal radiotherapy. Biochemical failure was defined as the nadir prostate-specific antigen (PSA) level plus 2 ng/mL. RESULTS: Of the 669 patients identified, 384 had undergone MP (57%) and 285 WP (42%) treatment, with a median PSA follow-up of 56 months. Of the 669 patients, 11%, 35%, and 54% were at low, intermediate, and high risk, respectively. The median dose was 75 Gy for the MP and 71 Gy for the WP groups. Of the MP and WP groups, 52% and 36% underwent hormonal therapy. The median BFFS and 5-year BFFS rate was 128 months and 73% for the MP group and 96 months and 58% for the WP group. The median PFS and 5-year PFS rate was 128 months and 72% for the MP group and 83 months and 56% for the WP group. Multivariate analysis revealed no difference between MP and WP treatment. However T stage, pretreatment PSA level, and Gleason score were significant predictors of BFFS and PFS. CONCLUSIONS: We observed no difference in outcomes between patients undergoing WP versus MP using three-dimensional conformal radiotherapy. Therefore, the exclusion of the common iliac lymph nodes in the treatment of patients with high-risk prostate cancer might be acceptable.

Liver function after irradiation based on computed tomographic portal vein perfusion imaging.

PURPOSE: To determine whether individual and regional liver sensitivity to radiation could be assessed by measuring liver perfusion during a course of treatment using dynamic contrast-enhanced computed tomography scanning. METHODS AND MATERIALS: Patients with intrahepatic cancer undergoing conformal radiotherapy underwent dynamic contrast-enhanced computed tomography (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) before, during, and 1 month after treatment. We hoped to determine whether the residual functioning liver (i.e., those regions showing portal vein perfusion) could be used to predict overall liver function after irradiation. RESULTS: Radiation doses from 45 to 84 Gy resulted in undetectable regional portal vein perfusion 1 month after treatment. The volume of each liver with undetectable portal vein perfusion ranged from 0 to 39% and depended both on the patient's sensitivity and on dose distribution. There was a significant correlation between indocyanine green clearance and the mean of the estimated portal vein perfusion in the functional liver parenchyma (p < 0.001). CONCLUSION: This study reveals substantial individual variability in the sensitivity of the liver to irradiation. In addition, these findings suggest that hepatic perfusion imaging may be a marker for liver function and has the potential to be a tool for individualizing therapy.

Percent positive biopsy cores as a prognostic factor for prostate cancer treated with external beam radiation.

OBJECTIVES: To examine the prognostic value of percent positive cores (PPC) in prostate cancer patients treated with external beam radiotherapy (RT). METHODS: An institutional review board-approved, retrospective analysis was conducted on 814 patients treated with RT with or without hormonal therapy between 1984 and 2002. Percent positive cores (number of positive cores divided by total number of cores) was calculable for 591 patients with a median follow-up of 65 months. Univariate and multivariable analyses were performed using Kaplan-Meier and Cox proportional hazard methods relating PPC to other risk factors, biochemical/clinical disease-free survival (PSA-DFS), prostate cancer-specific survival (DSS), and overall survival (OS). RESULTS: Percent positive cores was associated with stage, Gleason score (GS), pretreatment serum prostate-specific antigen (PSA) level, and use of adjunctive androgen suppression therapy. The 5-year PSA-DFS, DSS, and OS rates were 80%, 99%, and 91%, respectively, for patients with PPC less than 50%, compared with 56%, 94%, and 87% for patients with PPC 50% or greater (P <0.0001, <0.004, and <0.04, respectively). Multivariable analysis revealed that PPC, stage, GS, PSA, and androgen suppression therapy were all significantly associated with PSA-DFS, whereas only GS was associated with DSS and OS. For high, intermediate, and low-risk patients, 5-year PSA-DFS was 62% versus 39%, 80% versus 59%, and 90% versus 82% for PPC less than 50% versus PPC 50% or greater, respectively. CONCLUSIONS: Percent positive cores predicts outcome of prostate cancer patients treated with RT, independently of other known prognostic factors. Percent positive cores may have particular use for further risk stratification within established clinical risk categories.

Physical models and simpler dosimetric descriptors of radiation late toxicity.

Predicting radiation damage to specific organs is becoming ever more challenging with the use of intensity-modulated beams, nonuniform dose distributions, partial organ irradiation, and interpatient and even intraorgan variations in radiation sensitivity. Data-based physical models can be of use in summarizing complicated dose-volume data to help describe clinical outcomes and ultimately aid in the prediction of clinical toxicity. This article attempts to provide a brief overview of the use of normal tissue complication probability (NTCP) models and other simple dose/volume metrics to describe a few clinically significant complications (either frequent or serious) associated with radiation therapy of the head and neck, thorax, and abdominal-pelvic regions. Specifically, it reviews the application of these methods for late toxicities of the parotid, lung, heart, spinal cord, liver, and rectum. It focuses on organ-specific NTCP parameters as well as simple dosimetric descriptors that might be used to help treatment plan evaluation in clinical practice.