Head and neck cancers account for approximately 3% of all cancers in the United States with 62,000 new cases diagnosed annually. The global incidence is approximately 700,000 new cases a year. There ...has also been a recent increase in human papilloma virus–related oropharyngeal cancers. External beam radiation therapy (RT) is commonly used as an effective therapy for head and neck (H&N) cancers. This is used as a definitive treatment (alone or in combination with chemotherapy) or as an adjuvant treatment after surgical resection of the tumors. Because of the complex anatomy of the H&N region, several critical structures in and around the area receive radiation treatment. This includes the neural structures (brainstem, spinal cord, and brachial plexus), salivary glands, mucosa, major blood vessels, and swallowing musculature. Careful RT planning is necessary to avoid or mitigate the side effects of treatment. This review discusses some of the major acute and late side effects of RT for H&N cancers and provides evidence-based guidelines for their management. Patient-reported outcomes and quality-of-life implications are also discussed.
The American College of Chest Physicians (ACCP) produced an evidence-based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to ...American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations.
The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations.
The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements.
Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki.
To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, ...esophagus, spinal cord, ribs, and brachial plexus.
The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy and 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists.
Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed.
We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT.
To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first ...step toward MR-only radiation therapy treatment planning for brain cancer.
Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis.
On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone-air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort.
A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain.
To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer.
Between June ...2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy CIMRT) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT HIMRT); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed.
There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT.
The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.
To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core ...Quality of Life Questionnaire (EORTC QLQ-C30).
Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline.
Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively).
In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.
Recent advances in deep neural networks (DNNs) have unlocked opportunities for their application for automatic image segmentation. We have evaluated a DNN-based algorithm for automatic segmentation ...of the prostate gland on a large cohort of patient images.
Planning-CT data sets for 1114 patients with prostate cancer were retrospectively selected and divided into 2 groups. Group A contained 1104 data sets, with 1 physician-generated prostate gland contour for each data set. Among these image sets, 771 were used for training, 193 for validation, and 140 for testing. Group B contained 10 data sets, each including prostate contours delineated by 5 independent physicians and a consensus contour generated using the STAPLE method in the CERR software package. All images were resampled to a spatial resolution of 1 × 1 × 1.5 mm. A region (128 × 128 × 64 voxels) containing the prostate was selected to train a DNN. The best-performing model on the validation data sets was used to segment the prostate on all testing images. Results were compared between DNN and physician-generated contours using the Dice similarity coefficient, Hausdorff distances, regional contour distances, and center-of-mass distances.
The mean Dice similarity coefficients between DNN-based prostate segmentation and physician-generated contours for test data in Group A, Group B, and Group B-consensus were 0.85 ± 0.06 (range, 0.65-0.93), 0.85 ± 0.04 (range, 0.80-0.91), and 0.88 ± 0.03 (range, 0.82-0.92), respectively. The Hausdorff distance was 7.0 ± 3.5 mm, 7.3 ± 2.0 mm, and 6.3 ± 2.0 mm for Group A, Group B, and Group B-consensus, respectively. The mean center-of-mass distances for all 3 data set groups were within 5 mm.
A DNN-based algorithm was used to automatically segment the prostate for a large cohort of patients with prostate cancer. DNN-based prostate segmentations were compared to the consensus contour for a smaller group of patients; the agreement between DNN segmentations and consensus contour was similar to the agreement reported in a previous study. Clinical use of DNNs is promising, but further investigation is warranted.
The goal of radiation therapy is to reduce or eliminate tumor burden while sparing normal tissues from long-term injury. Thoracic radiation presents a unique challenge because of the inherent ...sensitivity of normal lung tissue to radiation. Damage to normal lung tissue presents a major obstacle in the treatment of individuals. To overcome this problem, a number of strategies are being used, including the modulation of dose volume, the use of image-guided radiotherapy, and the use of agents designed to reduce lung injury from radiation. Herein we discuss our current knowledge of the molecular and cellular events that occur after radiation therapy, the clinical manifestations of radiation-induced lung injury, current strategies to minimize lung injury, and recent experimental methods to reduce lung injury and their potential for translation into the clinic.
To describe and evaluate a method for generating synthetic computed tomography (synCT) images from magnetic resonance simulation (MR-SIM) data for accurate digitally reconstructed radiograph (DRR) ...generation and dose calculations in prostate cancer radiation therapy.
A retrospective evaluation was performed in 9 prostate cancer patients who had undergone MR-SIM in addition to CT simulation (CT-SIM). MR-SIM data were used to generate synCT images by using a novel, voxel-based weighted summation approach. A subset of patients was used for weight optimization, and the number of patients to use during optimization was determined. Hounsfield unit (HU) differences between CT-SIM and synCT images were analyzed via mean absolute error (MAE). Original, CT-based treatment plans were mapped onto synCTs. DRRs were generated, and agreement between CT and synCT-generated DRRs was evaluated via Dice similarity coefficient (DSC). Dose was recalculated, and dose-volume metrics and gamma analysis were used to evaluate resulting treatment plans.
Full field-of-view synCT MAE across all patients was 74.3 ± 10.9 HU with differences from CTs of 2.0 ± 8.1 HU and 11.9 ± 46.7 HU for soft tissue structures (prostate, bladder, and rectum) and femoral bones, respectively. Calculated DSCs for anterior-posterior and lateral DRRs were 0.90 ± 0.04 and 0.92 ± 0.05, respectively. Differences in D99%, mean dose, and maximum dose to the clinical target volume from CT-SIM dose calculations were 0.75% ± 0.35%, 0.63% ± 0.34%, and 0.54% ± 0.33%, respectively, for synCT-generated plans. Gamma analysis (2%/2 mm dose difference/distance to agreement) revealed pass rates of 99.9% ± 0.1% (range, 99.7%-100%).
Generated synCTs enabled accurate DRR generation and dose computation for prostate MR-only simulation. Dose recalculated on synCTs agreed well with original planning distributions. Further validation using a larger patient cohort is warranted.
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