Showing papers in "International Journal of Radiation Oncology Biology Physics in 2010"

Use of normal tissue complication probability models in the clinic.

Abstract: The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included.

Radiation Dose–Volume Effects in the Brain

Abstract: The literature is reviewed to identify the main clinical and dose-volume predictors for acute and late radiation-induced heart disease. A clear quantitative dose and/or volume dependence for most cardiac toxicity has not yet been shown, primarily because of the scarcity of the data. Several clinical factors, such as age, comorbidities and doxorubicin use, appear to increase the risk of injury. The existing dose-volume data is presented, as well as suggestions for future investigations to better define radiation-induced cardiac injury.

Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An Introduction to the Scientific Issues

Abstract: Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed.

Radiation dose-volume effects in the lung.

Abstract: The three-dimensional dose, volume, and outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold "tolerance dose-volume" levels. There are strong volume and fractionation effects.

Radiation Dose–Volume Effects in Radiation-Induced Rectal Injury

Abstract: The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving ≥60Gy is consistently associated with the risk of Grade ≥2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04–0.14); m = 0.13 (0.10–0.17); and TD50 = 76.9 (73.7–80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions.

Radiation-Associated Liver Injury

Abstract: 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.

Radiation-related heart disease: current knowledge and future prospects.

Abstract: INTRODUCTIONIt has been recognized since the 1960s that the heart may bedamaged by substantial doses of radiation [>30 Gray (Gy)],such as used to occur during mantle radiotherapy for Hodg-kin lymphoma. During the last few years, however, evidencethat radiation-related heart disease (RRHD) can occur fol-lowing doses below 20 Gy has emerged from several inde-pendent sources. Those sources include studies of breastcancer patients who received mean cardiac doses of 3 to 17Gy when given radiotherapy following surgery and studiesof survivors of the atomic bombings of Japan who receiveddoses of up to 4 Gy.At doses above 30 Gy, an increased risk of RRHD can be-comes apparent within a year or two of exposure, and the riskincreases with higher radiotherapy dose, younger age at irra-diation, and the presence of conventional risk factors. Atlower doses, the typical latency period is much longer andis often more than a decade. The nature and magnitude ofthe risk following lower doses is not well characterized,and it is not yet clear whether there is a threshold dose belowwhich there is no risk.The evidence regarding RRHD comes from several differ-ent disciplines. The present review brings together informa-tion from pathology, radiobiology, cardiology, radiationoncology, and epidemiology; it summarizes current knowl-edge, identifies gaps in that knowledge, and outlines somepotential strategies for filling them.CURRENT KNOWLEDGEPathologyThe pathological expressions of RRHD documented fol-lowing therapeutic irradiation can be broadly reduced tofour conditions: pericarditis, pericardial fibrosis, diffusemyocardial fibrosis, and coronary artery disease (CAD)(1, 2). Radiation may also cause valvular disease, althoughtheevidence for this isnotasstrong.None of these conditionsis specific to radiation.Radiation-related pericarditis is characterized by an exu-date of a variable amount of protein-rich fluid within thepericardial sac (pericardial effusion). Rapid accumulationof this fluid can, in rare cases, cause potentially fatal cardiactamponade. Almost invariably, fibrin accumulates on the

Radiotherapy dose-volume effects on salivary gland function.

Abstract: Publications relating parotid dose–volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. A lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.

Radiation Dose–Volume Effects in the Stomach and Small Bowel

Abstract: Published data suggest that the risk of moderately severe (≥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 dose-volume effects in the spinal cord.

Abstract: Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (alpha/beta = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen.

Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery

Abstract: Purpose To investigate the correlation between volume of brain irradiated by stereotactic radiosurgery (SRS) and the incidence of symptomatic and asymptomatic brain radionecrosis (RN). Methods and Materials A retrospective analysis was performed of patients treated with single-fraction SRS for brain metastases at our institution. Patients with at least 6-month imaging follow-up were included and diagnosed with RN according to a combination of criteria, including appearance on serial imaging and histology. Univariate and multivariate analyses were performed to determine the predictive value of multiple variables, including volume of brain receiving a specific dose (V8 Gy–V18 Gy). Results Sixty-three patients were reviewed, with a total of 173 lesions. Most patients (63%) had received previous whole-brain irradiation. Mean prescribed SRS dose was 18 Gy. Symptomatic RN was observed in 10% and asymptomatic RN in 4% of lesions treated. Multivariate regression analysis showed V8 Gy–V16 Gy to be most predictive of symptomatic RN (p < 0.0001). Threshold volumes for significant rise in RN rates occurred between the 75th and 90th percentiles, with a midpoint volume of 10.45 cm3 for V10 Gy and 7.85 cm3 for V12 Gy. Conclusions Analysis of patient and treatment variables revealed V8 Gy–V16 Gy to be the best predictors for RN using linear accelerator–based single-fraction SRS for brain metastases. We propose that patients with V10 Gy >10.5 cm3 or V12 Gy >7.9 cm3 be considered for hypofractionated rather than single-fraction treatment, to minimize the risk of symptomatic RN.

Results of a multi-institution deformable registration accuracy study (MIDRAS).

Abstract: Purpose To assess the accuracy, reproducibility, and computational performance of deformable image registration algorithms under development at multiple institutions on common datasets. Methods and Materials Datasets from a lung patient (four-dimensional computed tomography [4D-CT]), a liver patient (4D-CT and magnetic resonance imaging [MRI] at exhale), and a prostate patient (repeat MRI) were obtained. Radiation oncologists localized anatomic structures for accuracy assessment. Algorithm accuracy was determined by comparing the computer-predicted displacement at each bifurcation point with the displacement computed from the oncologists' annotations. Thirty-seven academic institutions and medical device manufacturers with published evidence of active deformable image registration capabilities were invited to participate. Results Twenty-seven groups agreed to participate; 6 did not return results. Sixteen completed the liver 4D-CT, 12 the lung 4D-CT, 3 the prostate MRI, and 3 the liver MRI-CT. The range of average absolute error for the lung 4D-CT was 0.6–1.2 mm (left–right [LR]), 0.5–1.8 mm (anterior–posterior [AP]), and 0.7–2.0 mm (superior–inferior [SI]); the liver 4D-CT was 0.8–1.5 mm (LR), 1.0–5.2 mm (AP), and 1.0–5.9 mm (SI); the liver MRI-CT was 1.1–2.6 mm (LR), 2.0–5.0 mm (AP), and 2.2–2.6 mm (SI); and the repeat prostate MRI prostate datasets was 0.5–6.2 mm (LR), 3.1–3.7 mm (AP), and 0.4–2.0 mm (SI). Conclusions An infrastructure was developed to assess multi-institution deformable registration accuracy. The results indicate large discrepancies in reported shifts, although the majority of deformable registration algorithms performed at an accuracy equivalent to the voxel size, promising to improve treatment planning, delivery, and assessment.

Radiation dose-volume effects of the urinary bladder.

Abstract: An in-depth overview of the normal-tissue radiation tolerance of the urinary bladder is presented. The most informative studies consider whole-organ irradiation. The data on partial-organ/nonuniform irradiation are suspect because the bladder motion is not accounted for, and many studies lack long enough follow-up data. Future studies are needed.

Development of RTOG Consensus Guidelines for the Definition of the Clinical Target Volume for Postoperative Conformal Radiation Therapy for Prostate Cancer

Abstract: Purpose To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer. Methods and Materials An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary “consensus” PF-CTV. Results Starting from the model-derived CTV, consensus was reached for a CT image–based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8–12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1–2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement. Conclusions Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT.

Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22).

Abstract: Purpose To assess the results of a multi-institutional study of intensity-modulated radiation therapy (IMRT) for early oropharyngeal cancer. Patients and Methods Patients with oropharyngeal carcinoma Stage T1–2, N0–1, M0 requiring treatment of the bilateral neck were eligible. Chemotherapy was not permitted. Prescribed planning target volumes (PTVs) doses to primary tumor and involved nodes was 66 Gy at 2.2 Gy/fraction over 6 weeks. Subclinical PTVs received simultaneously 54–60 Gy at 1.8–2.0 Gy/fraction. Participating institutions were preapproved for IMRT, and quality assurance review was performed by the Image-Guided Therapy Center. Results 69 patients were accrued from 14 institutions. At median follow-up for surviving patients (2.8 years), the 2-year estimated local-regional failure (LRF) rate was 9%. 2/4 patients (50%) with major underdose deviations had LRF compared with 3/49 (6%) without such deviations ( p = 0.04). All cases of LRF, metastasis, or second primary cancer occurred among patients who were current/former smokers, and none among patients who never smoked. Maximal late toxicities Grade ≥2 were skin 12%, mucosa 24%, salivary 67%, esophagus 19%, osteoradionecrosis 6%. Longer follow-up revealed reduced late toxicity in all categories. Xerostomia Grade ≥2 was observed in 55% of patients at 6 months but reduced to 25% and 16% at 12 and 24 months, respectively. In contrast, salivary output did not recover over time. Conclusions Moderately accelerated hypofractionatd IMRT without chemotherapy for early oropharyngeal cancer is feasible, achieving high tumor control rates and reduced salivary toxicity compared with similar patients in previous Radiation Therapy Oncology Group studies. Major target underdose deviations were associated with higher LRF rate.

Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

Abstract: Purpose Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)–based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results On average, the hippocampal avoidance volume was 3.3 cm3, occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy2 using helical tomotherapy and by 81% to 0.73 Gy2 using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers

Abstract: The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Volumetric modulated arc therapy improves dosimetry and reduces treatment time compared to conventional intensity-modulated radiotherapy for locoregional radiotherapy of left-sided breast cancer and internal mammary nodes.

Abstract: Purpose Volumetric modulated arc therapy (VMAT) is a novel extension of conventional intensity-modulated radiotherapy (cIMRT), in which an optimized three-dimensional dose distribution may be delivered in a single gantry rotation. VMAT is the predecessor to RapidArc (Varian Medical System). This study compared VMAT with cIMRT and with conventional modified wide-tangent (MWT) techniques for locoregional radiotherapy for left-sided breast cancer, including internal mammary nodes. Methods and Materials Therapy for 5 patients previously treated with 50 Gy/25 fractions using nine-field cIMRT was replanned with VMAT and MWT. Comparative endpoints were planning target volume (PTV) dose homogeneity, doses to surrounding structures, number of monitor units, and treatment delivery time. Results For VMAT, two 190° arcs with 2-cm overlapping jaws were required to optimize over the large treatment volumes. Treatment plans generated using VMAT optimization resulted in PTV homogeneity similar to that of cIMRT and MWT. The average heart volumes receiving >30 Gy for VMAT, cIMRT, and MWT were 2.6% ± 0.7%, 3.5% ± 0.8%, and 16.4% ± 4.3%, respectively, and the average ipsilateral lung volumes receiving >20 Gy were 16.9% ± 1.1%, 17.3% ± 0.9%, and 37.3% ± 7.2%, respectively. The average mean dose to the contralateral medial breast was 3.2 ± 0.6 Gy for VMAT, 4.3 ± 0.4 Gy for cIMRT, and 4.4 ± 4.7 Gy for MWT. The healthy tissue volume percentages receiving 5 Gy were significantly larger with VMAT (33.1% ± 2.1%) and IMRT (45.3% ± 3.1%) than with MWT (19.4% ± 3.7%). VMAT reduced the number of monitor units by 30% and the treatment time by 55% compared with cIMRT. Conclusions VMAT achieved similar PTV coverage and sparing of organs at risk, with fewer monitor units and shorter delivery time than cIMRT.

Radiation associated brainstem injury.

Abstract: Publications relating brainstem radiation toxicity to quantitative dose and dose–volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60–64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose–volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumes of the brainstem (1–10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions ≤2 Gy; however, the risk appears to increase markedly at doses >64 Gy.

Dose-Escalation Study of Single-Fraction Stereotactic Body Radiotherapy for Liver Malignancies

Abstract: Purpose We performed a Phase I dose-escalation study to explore the feasibility and safety of treating primary and metastatic liver tumors with single-fraction stereotactic body radiotherapy (SBRT) Methods and Materials Between February 2004 and February 2008, 26 patients were treated for 40 identifiable lesions Nineteen patients had hepatic metastases, 5 had intrahepatic cholangiocarcinomas, and 2 had recurrent hepatocellular carcinomas The prescribed radiation dose was escalated from 18 to 30 Gy at 4-Gy increments with a planned maximum dose of 30 Gy Cumulative incidence functions accounted for competing risks to estimate local failure (LF) incidence over time under the competing risk of death Results All patients tolerated the single-fraction SBRT well without developing a dose-limiting toxicity Nine acute Grade 1 toxicities, one acute Grade 2 toxicity, and two late Grade 2 gastrointestinal toxicities were observed After a median of 17 months follow-up (range, 2–55 months), the cumulative risk of LF at 12 months was 23% Fifteen patients have died: 11 treated for liver metastases and 4 with primary liver tumors died The median survival was 286 months, and the 2-year actuarial overall survival was 504% Conclusions It is feasible and safe to deliver single-fraction, high-dose SBRT to primary or metastatic liver malignancies measuring ≤5 cm Moreover, single-fraction SBRT for liver lesions demonstrated promising local tumor control with minimal acute and long-term toxicity Single-fraction SBRT appears to be a viable nonsurgical option, but further studies are warranted to evaluate both control rates and impact on quality of life

Quantification of the Relative Biological Effectiveness for Ion Beam Radiotherapy: Direct Experimental Comparison of Proton and Carbon Ion Beams and a Novel Approach for Treatment Planning

Abstract: Purpose: To present the first direct experimental in vitro comparison of the biological effectiveness of rangeequivalent protons and carbon ion beams for Chinese hamsterovary cells exposed in a three-dimensional phantom using a pencil beam scanning technique and to compare the experimental data with a novel biophysical model. Methodsand Materials:Cell survivalwasmeasuredinthe phantomafter irradiation withtwo opposingfields,thus mimicking the typical patient treatment scenario. The novel biophysical model represents a substantial extension of the local effect model, previously used for treatment planning in carbon ion therapy for more than 400 patients, and potentially can be used to predict effectiveness of all ion species relevant for radiotherapy. A key feature of the new approach is the more sophisticated consideration of spatially correlated damage induced by ion irradiation. Results: The experimental data obtained for Chinese hamster ovary cells clearly demonstrate that higher cell killing is achieved in the target region with carbon ions as compared with protons when the effects in the entrance channel are comparable. The model predictions demonstrate agreement with these experimental data and with data obtained with helium ions under similar conditions. Good agreement is also achieved with relative biological effectiveness values reported in the literature for other cell lines for monoenergetic proton, helium, and carbon ions. Conclusion: Both the experimental data and the new modeling approach are supportive of the advantages of carbon ions as compared with protons for treatment-like field configurations. Because the model predicts the effectiveness for several ion species with similar accuracy, it represents a powerful tool for further optimization and utilization of the potential of ion beams in tumor therapy. 2010 Elsevier Inc. Ion beam therapy, Relative biological effectiveness (RBE), Biophysical model, Treatment planning.

Influence of Technologic Advances on Outcomes in Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Receiving Concomitant Chemoradiotherapy

Abstract: Purpose In 2004, our institution began using four-dimensional computed tomography (4DCT) simulation and then intensity-modulated radiotherapy (IMRT) (4DCT/IMRT) instead of three-dimensional conformal radiotherapy (3DCRT) for the standard treatment of non–small-cell lung cancer (NSCLC). This retrospective study compares disease outcomes and toxicity in patients treated with concomitant chemotherapy and either 4DCT/IMRT or 3DCRT. Methods and Materials A total of 496 NSCLC patients have been treated at M. D. Anderson Cancer Center between 1999 and 2006 with concomitant chemoradiotherapy. Among these, 318 were treated with CT/3DCRT and 91 with 4DCT/IMRT. Both groups received a median dose of 63 Gy. Disease end points were locoregional progression (LRP), distant metastasis (DM), and overall survival (OS). Disease covariates were gross tumor volume (GTV), nodal status, and histology. The toxicity end point was Grade ≥3 radiation pneumonitis; toxicity covariates were GTV, smoking status, and dosimetric factors. Data were analyzed using Cox proportional hazards models. Results Mean follow-up times in the 4DCT/IMRT and CT/3DCRT groups were 1.3 (range, 0.1–3.2) and 2.1 (range, 0.1–7.9) years, respectively. The hazard ratios for 4DCT/IMRT were Conclusions Treatment with 4DCT/IMRT was at least as good as that with 3DCRT in terms of the rates of freedom from LRP and DM. There was a significant reduction in toxicity and a significant improvement in OS.

A Prospective Phase III Randomized Trial of Hypofractionation Versus Conventional Fractionation in Patients With High-Risk Prostate Cancer

Abstract: Purpose To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer. Methods and Materials From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients received a 9-month course of total androgen deprivation (TAD), and radiotherapy started 2 months thereafter. Results The median (range) follow-up was 32 (8–66) and 35 (7–64) months in the hypofractionation and conventional fractionation arms, respectively. No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups, respectively. The 3-year freedom from biochemical failure (FFBF) rates were 87% and 79% in the hypofractionation and conventional fractionation groups, respectively ( p = 0.035). The 3-year FFBF rates in patients at a very high risk ( i.e., pretreatment prostate-specific antigen (iPSA) >20 ng/mL, Gleason score ≥8, or T ≥2c), were 88% and 76% ( p = 0.014) in the former and latter arm, respectively. The multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as significant prognostic factors. Conclusions Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF.

Intensity-Modulated Proton Therapy Reduces the Dose to Normal Tissue Compared With Intensity-Modulated Radiation Therapy or Passive Scattering Proton Therapy and Enables Individualized Radical Radiotherapy for Extensive Stage IIIB Non-Small-Cell Lung Cancer: A Virtual Clinical Study

Abstract: Purpose To compare dose volume histograms of intensity-modulated proton therapy (IMPT) with those of intensity-modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT) for the treatment of stage IIIB non-small-cell lung cancer (NSCLC) and to explore the possibility of individualized radical radiotherapy. Methods and Materials Dose volume histograms designed to deliver IMRT at 60 to 63 Gy, PSPT at 74 Gy, and IMPT at the same doses were compared and the use of individualized radical radiotherapy was assessed in patients with extensive stage IIIB NSCLC (n = 10 patients for each approach). These patients were selected based on their extensive disease and were considered to have no or borderline tolerance to IMRT at 60 to 63 Gy, based on the dose to normal tissue volume constraints (lung volume receiving 20 Gy [V20] of Results Compared with IMRT, IMPT spared more lung, heart, spinal cord, and esophagus, even with dose escalation from 63 Gy to 83.5 Gy, with a mean MTD of 74 Gy. Compared with PSPT, IMPT allowed further dose escalation from 74 Gy to a mean MTD of 84.4 Gy (range, 79.4–88.4 Gy) while all parameters of normal tissue sparing were kept at lower or similar levels. In addition, IMPT prevented lower-dose target coverage in patients with complicated tumor anatomies. Conclusions IMPT reduces the dose to normal tissue and allows individualized radical radiotherapy for extensive stage IIIB NSCLC.

Chest wall volume receiving >30 Gy predicts risk of severe pain and/or rib fracture after lung stereotactic body radiotherapy.

Abstract: Purpose To identify the dose–volume parameters that predict the risk of chest wall (CW) pain and/or rib fracture after lung stereotactic body radiotherapy. Methods and Materials From a combined, larger multi-institution experience, 60 consecutive patients treated with three to five fractions of stereotactic body radiotherapy for primary or metastatic peripheral lung lesions were reviewed. CW pain was assessed using the Common Toxicity Criteria for pain. Peripheral lung lesions were defined as those located within 2.5 cm of the CW. A minimal point dose of 20 Gy to the CW was required. The CW volume receiving ≥20, ≥30, ≥40, ≥50, and ≥60 Gy was determined and related to the risk of CW toxicity. Results Of the 60 patients, 17 experienced Grade 3 CW pain and five rib fractures. The median interval to the onset of severe pain and/or fracture was 7.1 months. The risk of CW toxicity was fitted to the median effective concentration dose–response model. The CW volume receiving 30 Gy best predicted the risk of severe CW pain and/or rib fracture (R 2 = 0.9552). A volume threshold of 30 cm 3 was observed before severe pain and/or rib fracture was reported. A 30% risk of developing severe CW toxicity correlated with a CW volume of 35 cm 3 receiving 30 Gy. Conclusion The development of CW toxicity is clinically relevant, and the CW should be considered an organ at risk in treatment planning. The CW volume receiving 30 Gy in three to five fractions should be limited to 3 , if possible, to reduce the risk of toxicity without compromising tumor coverage.

Radiation Dose-Volume Effects in the Esophagus

Abstract: Publications relating esophageal radiation toxicity to clinical variables and to quantitative dose and dose–volume measures derived from three-dimensional conformal radiotherapy for non–small-cell lung cancer are reviewed. A variety of clinical and dosimetric parameters have been associated with acute and late toxicity. Suggestions for future studies are presented.

Radiation-Associated Kidney Injury

Abstract: 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.

Late Side Effects and Quality of Life After Radiotherapy for Rectal Cancer

Abstract: Purpose There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort ( n = 535). Methods and Materials All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Results Median time since surgery was 4.8 years. Radiation-treated (RT+) patients ( n = 199) had increased bowel frequency compared with non–radiation-treated (RT−) patients ( n = 336); 19% vs. 6% had more than eight daily bowel movements ( p n = 69) compared with RT− patients ( n = 240), were incontinent for liquid stools (49% vs. 15%, p p p p = 0.001). Radiation-treated patients had worse social function than RT− patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function ( p Conclusions Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation.

Abstract: Purpose To report interim cosmetic results and toxicity from a prospective study evaluating accelerated partial-breast irradiation (APBI) administered using a highly conformal external beam approach. Methods and Materials We enrolled breast cancer patients in an institutional review board–approved prospective study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep-inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice daily. Dosimetric parameters in patients who maintained acceptable cosmesis were compared with those in patients developing unacceptable cosmesis in follow-up, using t -tests. Results Thirty-four patients were enrolled; 2 were excluded from analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years, new unacceptable cosmesis developed in 7 patients, leading to early study closure. We compared patients with new unacceptable cosmesis with those with consistently acceptable cosmesis. Retrospective analysis demonstrated that all but one plan adhered to the dosimetric requirements of the national APBI trial. The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50) was lower in patients with acceptable cosmesis than in those with unacceptable cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference volume receiving 38.5 Gy (V100) was also lower in patients with acceptable cosmesis (15.5% vs. 23.0%; p = 0.02). Conclusions The hypofractionated schedule and parameters commonly used for external beam APBI and prescribed by the ongoing national trial may be suboptimal, at least when highly conformal techniques such as IMRT with management of breathing motion are used. The V50 and V100 of the breast reference volume seem correlated with cosmetic outcome, and stricter limits may be appropriate in this setting.