Conformal Avoidance of Normal Organs at Risk by Perfusion-Modulated Dose Sculpting in Tumor Single-Dose Radiation Therapy.

PURPOSE: Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ∼50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTVHD]), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTVPMDS]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTVPMDS may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose. METHODS AND MATERIALS: Dose fall-off within the PTVPMDS penumbra of oligometastatic lesions was planned and delivered by intensity modulated inverse dose painting. SDRT- and SDRT-PMDS-treated lesions were followed with periodic positron emission tomography/computed tomography imaging to assess local tumor control. RESULTS: Cumulative baseline 5-year local relapse rates of oligometastases treated with 24 Gy SDRT alone (8% relapses, n = 292) were similar in moderate PTVPMDS dose-sculpted (23-18 Gy, n = 76, 11% relapses, P = .36) and extreme dose-sculpted (<18 Gy, n = 61, 14% relapses, P = .29) lesions, provided the major 24 Gy PTVHD constituted ≥60% of the total PTV. In contrast, 28% of local relapses occurred in 26 extreme dose-sculpted PTVPMDS lesions when PTVHD constituted <60% of the total PTV (P = .004), suggesting a threshold for the PTVPMDS bystander effect. CONCLUSION: The study provides compelling clinical support for the bystander radiosensitization hypothesis, rendering local cure of tumor lesions despite a ≥25% PTVPMDS dose reduction of the 24 Gy PTVHD dose, adapted to conformally meet OAR dose/volume constraints. The SDRT-PMDS approach thus provides a therapeutic resolution to otherwise radioablation-intractable oligometastatic disease.

Comparison of statistical machine learning models for rectal protocol compliance in prostate external beam radiation therapy.

PURPOSE: Limiting the dose to the rectum can be one of the most challenging aspects of creating a dosimetric external beam radiation therapy (EBRT) plan for prostate cancer treatment. Rectal sparing devices such as hydrogel spacers offer the prospect of increased space between the prostate and rectum, causing reduced rectal dose and potentially reduced injury. This study sought to help identify patients at higher risk of developing rectal injury based on estimated rectal dosimetry compliance prior to the EBRT simulation and planning procedure. Three statistical machine learning methods were compared for their ability to predict rectal dose outcomes with varied classification thresholds applied. METHODS: Prostate cancer patients treated with conventionally fractionated EBRT to a reference dose of 74-78 Gy were invited to participate in the study. The dose volume histogram data from each dosimetric plan was used to quantify planned rectal volume receiving 50%, 83% 96%, and 102% of the reference dose. Patients were classified into two groups for each of these dose levels: either meeting tolerance by having a rectal volume less than a clinically acceptable threshold for the dose level (Y) or violating the tolerance by having a rectal volume greater than the threshold for the dose level (N). Logistic regression, classification and regression tree, and random forest models were compared for their ability to discriminate between class outcomes. Performance metrics included area under the receiver operator characteristic curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. Finally, three classification threshold levels were evaluated for their impact on model performance. RESULTS: A total of 176 eligible participants were recruited. Variable importance differed between model methods. Area under the receiver operator characteristic curve performance varied greatly across the different rectal dose levels and between models. Logistic regression performed best at the 83% reference dose level with an AUC value of 0.844, while random forest demonstrated best discrimination at the 96% reference dose level with an AUC value of 0.733. In addition to the standard classification probability threshold of 50%, the clinically representative threshold of 10%, and the best threshold from each AUC plot was applied to compare metrics. This showed that using a 50% threshold and the best threshold from the AUC plots yields similar results. Conversely, applying the more conservative clinical threshold of 10% maximized the sensitivity at V83_RD and V96_RD for all model types. Based on the combination of the metrics, logistic regression would be the recommendation for rectal protocol compliance prediction at the 83% reference dose level, and random forest for the 96% reference dose level, particularly when using the clinical probability threshold of 10%. CONCLUSIONS: This study demonstrated the efficacy of statistical machine learning models on rectal protocol compliance prediction for prostate cancer EBRT dosimetric planning. Both logistic regression and random forest modeling approaches demonstrated good discriminative ability for predicting class outcomes in the upper dose levels. Application of a conservative clinical classification threshold maximized sensitivity and further confirmed the value of logistic regression and random forest models over classification and regression tree.

Mitigating Respiratory Motion in Radiation Therapy: Rapid, Shallow, Non-invasive Mechanical Ventilation for Internal Thoracic Targets.

PURPOSE: Reducing respiratory motion during the delivery of radiation therapy reduces the volume of healthy tissues irradiated and may decrease radiation-induced toxicity. The purpose of this study was to assess the potential for rapid shallow non-invasive mechanical ventilation to reduce internal anatomy motion for radiation therapy purposes. METHODS AND MATERIALS: Ten healthy volunteers (mean age, 38 years; range, 22-54 years; 6 female and 4 male) were scanned using magnetic resonance imaging during normal breathing and at 2 ventilator-induced frequencies: 20 and 25 breaths per minute for 3 minutes. Sagittal and coronal cinematic data sets, centered over the right diaphragm, were used to measure internal motions across the lung-diaphragm interface. Repeated scans assessed reproducibility. Physiologic parameters and participant experiences were recorded to quantify tolerability and comfort. RESULTS: Physiologic observations and experience questionnaires demonstrated that rapid shallow non-invasive ventilation technique was tolerable and comfortable. Motion analysis of the lung-diaphragm interface demonstrated respiratory amplitudes and variations reduced in all subjects using rapid shallow non-invasive ventilation compared with spontaneous breathing: mean amplitude reductions of 56% and 62% for 20 and 25 breaths per minute, respectively. The largest mean amplitude reductions were found in the posterior of the right lung; 40.0 mm during normal breathing to 15.5 mm (P < .005) and 15.2 mm (P < .005) when ventilated with 20 and 25 breaths per minute, respectively. Motion variations also reduced with ventilation; standard deviations in the posterior lung reduced from 14.8 mm during normal respiration to 4.6 mm and 3.5 mm at 20 and 25 breaths per minute, respectively. CONCLUSIONS: To our knowledge, this study is the first to measure internal anatomic motion using rapid shallow mechanical ventilation to regularize and minimize respiratory motion over a period long enough to image and to deliver radiation therapy. Rapid frequency and shallow, non-invasive ventilation both generate large reductions in internal thoracic and abdominal motions, the clinical application of which could be profound-enabling dose escalation (increasing treatment efficacy) or high-dose ablative radiation therapy.

Effectiveness of robot-assisted training added to conventional rehabilitation in patients with humeral fracture early after surgical treatment: protocol of a randomised, controlled, multicentre trial.

BACKGROUND: The incidence of proximal humeral fractures increases with age. The functional recovery of the upper arm after such fractures is slow, and results are often disappointing. Treatment is associated with long immobilisation periods. Evidence-based exercise guidelines are missing. Loss of muscle mass as well as reduced range of motion and motor performance are common consequences. These losses could be partly counteracted by training interventions using robot-assisted arm support of the affected arm derived from neurorehabilitation. Thus, shorter immobilisation could be reached. Thus far, this approach has been tested in only a few small studies. The aim of the present study is to examine whether assistive robotic training augmenting conventional occupational and physical therapy can improve functional shoulder outcomes. METHODS/DESIGN: Patients aged between 35 and 66 years with proximal humeral fracture and surgical treatment will be recruited at three different clinics in Germany and randomised into an intervention group and a control group. Participants will be assessed before randomisation and followed after completing an intervention period of 3 weeks and additionally after 3, 6 and 12 months. The baseline assessment will include cognition (Short Orientation-Memory-Concentration Test); level of pain in the affected arm; ability to work; gait speed (10-m walk); disability of the arm, shoulder and hand (Disabilities of the Arm, Shoulder and Hand Outcome Measure [DASH]); range of motion of the affected arm (goniometer measurement); visual acuity; and motor function of orthopaedic patients (Wolf Motor Function Test-Orthopaedic version [WMFT-O]). Clinical follow-up directly after the intervention will include assessment of disability of the arm, shoulder and hand (DASH) as well as range of motion and motor function (WMFT-O). The primary outcome parameter will be the DASH, and the secondary outcome parameter will be the WMFT-O. The long-term results will be assessed prospectively by postal follow-up. All patients will receive conventional occupational and physical therapy. The intervention group will receive additional robot-assisted training using the Armeo®Spring robot for 3 weeks. DISCUSSION: This study protocol describes a phase II, randomised, controlled, single-blind, multicentre intervention study. The results will guide and possibly improve methods of rehabilitation after proximal humeral fracture. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03100201 . Registered on 28 March 2017.

Palliative treatment of pelvic bone tumors using radioiodine (125I) brachytherapy.

BACKGROUND: Complete resection of pelvic bone tumors, especially recurrent and metastatic ones, is often impossible to achieve using conventional surgery. This study aimed to assess the benefits and adverse effects of computed tomography (CT)-guided radioiodine (125I) brachytherapy for inoperable recurrent and metastatic bone tumors of the pelvis. METHODS: This was a retrospective study of 22 patients with confirmed pelvic bone tumors (10 females and 12 males; 15-84 years; 21 with primary pelvic tumor and one with pelvic metastasis). CT-guided 125I brachytherapy was performed using 9-21 125I seeds (radioactivity of 0.5-0.7 mCi). Seed implantation was validated by postoperative CT scanning. Complications, pain, survival, and CT-estimated tumor size were carried out to evaluate the therapeutic benefits. RESULTS: Postoperative CT scans revealed satisfactory 125I seed implantation, and the radiation dose delivered to 90% of the target area (D90) was higher than the prescription dose (PD). No obvious complications were observed. Pain was reported by 19 of 22 patients, but 17 reported pain relief after implantation. Follow-up ranged 8-27 (median, 19) months. Tumor size was reduced in 11 patients within 1 month after surgery, nine patients showed no change, and tumor size increased in two patients. Finally, 1- and 2-year survival was 81.8 and 45.5%, respectively; 1- and 2-year local tumor control rates were 59.1 and 36.4%, respectively. CONCLUSIONS: 125I seed implantation significantly reduced bone tumor size and relieved pain, with a low complication rate. These findings suggest that 125I brachytherapy treatment could be a useful palliative approach for pelvic bone tumor treatment.

Concurrent use of strontium-89 with external beam radiotherapy for multiple bone metastases: early experience.

OBJECTIVE: The aim of the present study was to consider the safety and efficacy of concurrent use of strontium-89 (Sr-89) with external beam radiotherapy (EBRT) for multiple bone metastases, including lesions that require urgent therapy. METHODS: A retrospective review was performed of a consecutive series of patients who received Sr-89 for multiple bone metastases. Forty-five patients with multiple bone metastases received Sr-89 injection. Since 17 of the 45 patients had osteolytic bone lesions requiring emergent EBRT, they underwent concurrent use of Sr-89 with EBRT (concurrent group). The remaining 28 patients, none of whom had osteolytic lesions requiring urgent EBRT, were given Sr-89 injection only (singularity group). The injection of Sr-89 was to be given during EBRT, or on the day before the first day of EBRT. The dose of EBRT was 30 Gy in 10 fractions or 40 Gy in 20 fractions. Adverse events were evaluated according to hematological toxicity as measured by the Common Terminology Criteria for Adverse Events (V4.0). To assess efficacy, we checked changes in the pain scale and analgesic drug dosages, and the presence or absence of serious complications from bone metastases. RESULTS: Fifteen of 17 patients (88.2%) in the concurrent group and 17 of 28 patients (60.7%) in the singularity group reported bone pain relief. A statistically significant difference was found between the two groups, and severe complications (spinal cord compression and pathological fracture) from bone metastases could be prevented in all patients in the concurrent group. Severe hematological toxicity (grade 3 or higher) was not observed in the two groups. There was no statistical difference between the two groups. No one required additional intervention. The adverse events were tolerable. CONCLUSIONS: The results of our study suggest that concurrent use of Sr-89 with EBRT for multiple bone metastases can be performed safely if it is carried out with care, and that it may be an effective therapy in cases requiring emergency treatment.

Tolerance and dose-volume relationship of intrathoracic stomach irradiation after esophagectomy for patients with thoracic esophageal squamous cell carcinoma.

PURPOSE: To identify the tolerance of radiation with a high prescribed dose and predictors for the development of intrathoracic stomach toxicity in patients with thoracic esophageal squamous cell carcinoma (SCC) after esophagectomy followed by gastric conduit reconstruction. MATERIALS AND METHODS: From 2011 to 2013, 105 patients after esophagectomy were treated with postoperative radiotherapy. The intrathoracic stomach was outlined with the calculation of a dose-volume histogram (DVH) for the initial intended treatment of 6020 cGy or 6300 cGy. The volume of the intrathoracic stomach receiving each dose was recorded at 10-Gy intervals between 10 and 40 Gy and at 5-Gy intervals between 40 and 60 Gy. The grade of toxicities was defined by the National Cancer Institute Common Toxicity Criteria version 4.0. RESULTS: The mean and maximum doses of the intrathoracic stomach were 2449 ± 986 cGy and 6519 ± 406 cGy, respectively. Sixteen (15.2%) and three (2.9%) experienced Common Toxicity Criteria Grade 2 and Grade 3 acute gastric toxicity. There were no Grade 4 toxicities. Fourteen patients (13.3%) exhibited late gastric complications possibly related to radiation. The volume percent of the intrathoracic stomach receiving at least 50 Gy (V50) was strongly associated with the degree of toxicity (p = 0.024, respectively). Multivariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicities. CONCLUSIONS: The intrathoracic stomach is well tolerated with a high-dose irradiation for patients with esophageal SCC receiving radiotherapy after esophagectomy. A strong dose-volume relationship exists for the development of Grade 2 acute intrathoracic stomach toxicity in our study.

Hypertrophic olivary degeneration resulting from posterior fossa masses and their treatments.

PURPOSE: Characterize hypertrophic olivary degeneration (HOD) that develops from posterior fossa masses and their treatments. METHODS: Retrospectively reviewed MR images and clinical data of 10 patients with posterior fossa masses and HOD. RESULTS: Eight patients had cerebellar lesions, and two patients had pontine lesions. Lesions consisted of tumors, demyelination, and nonspecific necrosis. MRI showed T2 hyperintense signal in the inferior olive a median 86 days after the diagnosis of a posterior fossa lesion. HOD presented prior to surgery (n=2), after surgery (n=3), after surgery/radiation therapy (n=4), or without treatment (n=1). CONCLUSIONS: HOD may develop from posterior fossa masses and surgical and/or radiation therapy.

A Randomized Pilot Trial Comparing Position Emission Tomography (PET)-Guided Dose Escalation Radiotherapy to Conventional Radiotherapy in Chemoradiotherapy Treatment of Locally Advanced Nasopharyngeal Carcinoma.

BACKGROUND: This pilot trial is designed to determine whether PET/CT-guided radiotherapy dose escalation can improve local control while minimizing toxicity for the treatment of locally advanced nasopharyngeal carcinoma. METHODS: 67 patients were randomized into the three treatment arms: conventional chemoradiotherapy (group A), CT-guided dose escalation chemoradiotherapy (group B) and PET/CT-guided dose escalation chemoradiotherapy (group C). Radiotherapy was delivered using the simultaneous modulated accelerated radiation therapy (SMART) technique in the dose-escalation treatment arms. Patients received concurrent and adjuvant chemotherapy. RESULTS: The use of PET/CT significantly changed the treatment volume delineation of the gross tumor volume. 3-year local progression-free (LPF) survival rates of three groups were 83.3%, 90.9% and 100%, respectively. The 3-year regional progression-free survival (RPFS) rates were 95.8%, 95.5% and 100%, respectively. The 3-year disease free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. The 3-year overall survival (OS) rates were 83.3%, 90.9% and 95.2%, respectively. The 3-year disease-free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. No patient had grade 4 late toxicity. CONCLUSIONS: PET/CT-guided dose escalation radiotherapy is well-tolerated and appears to be superior to conventional chemoradiotherapy for locally advanced NPC. TRIAL REGISTRATION: ClinicalTrials.gov NCT02089204.

3D calculation of radiation-induced second cancer risk including dose and tissue response heterogeneities.

PURPOSE: Tools for comparing relative induced second cancer risk, to inform choice of radiotherapy treatment plan, are becoming increasingly necessary as the availability of new treatment modalities expands. Uncertainties, in both radiobiological models and model parameters, limit the confidence of such calculations. The aim of this study was to develop and demonstrate a software tool to produce a malignant induction probability (MIP) calculation which incorporates patient-specific dose and allows for the varying responses of different tissue types to radiation. METHODS: The tool has been used to calculate relative MIPs for four different treatment plans targeting a subtotally resected meningioma: 3D conformal radiotherapy (3DCFRT), volumetric modulated arc therapy (VMAT), intensity-modulated x-ray therapy (IMRT), and scanned protons. RESULTS: Two plausible MIP models, with considerably different dose-response relationships, were considered. A fractionated linear-quadratic induction and cell-kill model gave a mean relative cancer risk (normalized to 3DCFRT) of 113% for VMAT, 16% for protons, and 52% for IMRT. For a linear no-threshold model, these figures were 105%, 42%, and 78%, respectively. The relative MIP between plans was shown to be significantly more robust to radiobiological parameter uncertainties compared to absolute MIP. Both models resulted in the same ranking of modalities, in terms of MIP, for this clinical case. CONCLUSIONS: The results demonstrate that relative MIP is a useful metric with which treatment plans can be ranked, regardless of parameter- and model-based uncertainties. With further validation, this metric could be used to discriminate between plans that are equivalent with respect to other planning priorities.

Automated contouring error detection based on supervised geometric attribute distribution models for radiation therapy: a general strategy.

PURPOSE: One of the most critical steps in radiation therapy treatment is accurate tumor and critical organ-at-risk (OAR) contouring. Both manual and automated contouring processes are prone to errors and to a large degree of inter- and intraobserver variability. These are often due to the limitations of imaging techniques in visualizing human anatomy as well as to inherent anatomical variability among individuals. Physicians/physicists have to reverify all the radiation therapy contours of every patient before using them for treatment planning, which is tedious, laborious, and still not an error-free process. In this study, the authors developed a general strategy based on novel geometric attribute distribution (GAD) models to automatically detect radiation therapy OAR contouring errors and facilitate the current clinical workflow. METHODS: Considering the radiation therapy structures' geometric attributes (centroid, volume, and shape), the spatial relationship of neighboring structures, as well as anatomical similarity of individual contours among patients, the authors established GAD models to characterize the interstructural centroid and volume variations, and the intrastructural shape variations of each individual structure. The GAD models are scalable and deformable, and constrained by their respective principal attribute variations calculated from training sets with verified OAR contours. A new iterative weighted GAD model-fitting algorithm was developed for contouring error detection. Receiver operating characteristic (ROC) analysis was employed in a unique way to optimize the model parameters to satisfy clinical requirements. A total of forty-four head-and-neck patient cases, each of which includes nine critical OAR contours, were utilized to demonstrate the proposed strategy. Twenty-nine out of these forty-four patient cases were utilized to train the inter- and intrastructural GAD models. These training data and the remaining fifteen testing data sets were separately employed to test the effectiveness of the proposed contouring error detection strategy. RESULTS: An evaluation tool was implemented to illustrate how the proposed strategy automatically detects the radiation therapy contouring errors for a given patient and provides 3D graphical visualization of error detection results as well. The contouring error detection results were achieved with an average sensitivity of 0.954/0.906 and an average specificity of 0.901/0.909 on the centroid/volume related contouring errors of all the tested samples. As for the detection results on structural shape related contouring errors, an average sensitivity of 0.816 and an average specificity of 0.94 on all the tested samples were obtained. The promising results indicated the feasibility of the proposed strategy for the detection of contouring errors with low false detection rate. CONCLUSIONS: The proposed strategy can reliably identify contouring errors based upon inter- and intrastructural constraints derived from clinically approved contours. It holds great potential for improving the radiation therapy workflow. ROC and box plot analyses allow for analytically tuning of the system parameters to satisfy clinical requirements. Future work will focus on the improvement of strategy reliability by utilizing more training sets and additional geometric attribute constraints.

Bilateral breast radiation delivered with static angle tomotherapy (TomoDirect): clinical feasibility and dosimetric results of a single patient.

We herein report on a case of synchronous bilateral breast cancer patient undergoing adjuvant intensity-modulated whole breast with static angle tomotherapy (TomoDirect). The patient was treated with a hypofractionated schedule employing a simultaneous integrated boost approach. Radiotherapy schedule was 45 Gy/20 fractions (2.25 Gy daily) to the bilateral whole breast and 50 Gy/20 fractions (2.5 Gy daily) to the 2 lumpectomy cavities. Treatment was delivered over 4 weeks. Dosimetric results were robust with consistent target coverage and adequate normal tissue avoidance. Treatment was generally well-tolerated and acute toxicity profile was mild. The present report highlights the promising clinical feasibility of TomoDirect for bilateral breast irradiation.

Monitoring ABC-assisted deep inspiration breath hold for left-sided breast radiotherapy with an optical tracking system.

PURPOSE: Recent knowledge on the effects of cardiac toxicity warrants greater precision for left-sided breast radiotherapy. Different breath-hold (BH) maneuvers (abdominal vs thoracic breathing) can lead to chest wall positional variations, even though the patient's tidal volume remains consistent. This study aims to investigate the feasibility of using optical tracking for real-time quality control of active breathing coordinator (ABC)-assisted deep inspiration BH (DIBH). METHODS: An in-house optical tracking system (OTS) was used to monitor ABC-assisted DIBH. The stability and localization accuracy of the OTS were assessed with a ball-bearing phantom. Seven patients with left-sided breast cancer were included. A free-breathing (FB) computed tomography (CT) scan and an ABC-assisted BH CT scan were acquired for each patient. The OTS tracked an infrared (IR) marker affixed over the patient's xiphoid process to measure the positional variation of each individual BH. Using the BH within which the CT scan was performed as the reference, the authors quantified intra- and interfraction BH variations for each patient. To estimate the dosimetric impact of BH variations, the authors studied the positional correlation between the marker and the left breast using the FB CT and BH CT scans. The positional variations of 860 BHs as measured by the OTS were retrospectively incorporated into the original treatment plans to evaluate their dosimetric impact on breast and cardiac organs [heart and left anterior descending (LAD) artery]. RESULTS: The stability and localization accuracy of the OTS was within 0.2 mm along each direction. The mean intrafraction variation among treatment BHs was less than 2.8 mm in all directions. Up to 12.6 mm anteroposterior undershoot, where the patient's chest wall displacement of a BH is less than that of a reference BH, was observed with averages of 4.4, 3.6, and 0.1 mm in the anteroposterior, craniocaudal, and mediolateral directions, respectively. A high positional correlation between the marker and the breast was found in the anteroposterior and craniocaudal directions with respective Pearson correlation values of 0.95 and 0.93, but no mediolateral correlation was found. Dosimetric impact of BH variations on breast coverage was negligible. However, the mean heart dose, mean LAD dose, and max LAD dose were estimated to increase from 1.4/7.4/18.6 Gy (planned) to 2.1/15.7/31.0 Gy (delivered), respectively. CONCLUSIONS: In ABC-assisted DIBH, large positional variation can occur in some patients, due to their different BH maneuvers. The authors' study has shown that OTS can be a valuable tool for real-time quality control of ABC-assisted DIBH.

Impact of post-operative radiation on coronary arteries in patients of early breast cancer: A pilot dosimetric study from a tertiary cancer care center from India.

BACKGROUND: The significant impact of postoperative radiotherapy (PORT) on cardiac morbidity in patients of early breast cancer (EBC) undergoing breast-conserving surgery has been shown in different studies. The present study was conducted to assess the impact of surgery and the side of involvement on radiation dose to left anterior descending artery (LAD) and Left circumflex coronary artery (LCx). MATERIALS AND METHODS: Totally, 58 patients of EBC were randomly chosen for this dosimetric study and planned with tangential field technique without intensity modulation (IM). Heart, LAD, and LCx (n = 55) were contoured. Dose volume histograms were analyzed to determine the Dmax (maximum dose) and Dmean (mean dose) of LAD and LCx. Student's t-test was used for comparative analysis of the means. RESULTS: The mean Dmax of LAD for left (L) EBC was 3.17 Gray (Gy) while for right (R) EBC it was 0.86 Gy (P = 0.007; 95% C.I, 1.14-3.48). The mean Dmean of LAD for L-EBC and R-EBC were 1.97 Gy and 0.79 Gy, respectively (P = 0.029; 95% C.I, 0.77-1.60). The mean-Dmax of LCx for patients with L-EBC (2.9 Gy; range: 1.2-4.35 Gy) was statistically higher than that for R-EBC (1.3 Gy; range: 0.7-3.2 Gy) (P = 0.045). The mean-Dmean of LCx for L-EBC (2.1 Gy; range: 0.6-3.6 Gy) was also significantly higher than that of L-EBC (0.9 Gy; range: 0.7-2.1 Gy) (P = 0.03). There was no significant impact of the pattern of surgery on LAD dose, but significance was noted for LCx dose parameters (P = 0.04 and 0.08 for m-Dmax and m-Dmean of LCx). CONCLUSION: This pilot dosimetric study confirms the assumption that patients with left-sided EBC are at higher risk of developing long-term cardiac morbidity when treated with PORT due to increased dose to LAD.

Taste dysfunction and eating behaviors in survivors of head and neck cancer treatment.

Radiation, chemotherapy, and surgery result in eating problems for patients with head and neck cancer. Eating is essential to physical and social functioning. Strategies for head and neck cancer survivors to cope with eating and taste impairments are reported in this study.

Fifty years of progress in radiation therapy for breast cancer.

Fifty years ago, radiation therapy (RT) was only used after mastectomy in patients with high-risk disease. The equipment, treatment planning, and treatment delivery were rudimentary compared to what is available today. In retrospect, the deleterious effects of the RT back then negated its benefits. The strategy of combining lesser surgery with RT (and adjuvant systemic therapy) has been successfully employed in breast-conserving therapy (BCT) and in avoiding axillary lymph node dissection in patients with 1 or 2 involved sentinel nodes. Local recurrence rates at 10 years following BCT are now similar to those following mastectomy. RT after breast-conserving surgery and after mastectomy has been demonstrated to not only decrease local-regional recurrence but also decrease distant metastases and improve long-term survival. The development of effective adjuvant systemic therapy has made RT not only more effective but also arguably more important. If systemic therapy is effective at addressing micro-metastatic disease, then obtaining local tumor control becomes even more important. Moderately hypofractionated RT (2.66 Gy per day) is just as safe and effective as conventional fractionation shortening BCT from 6 weeks to 3-4 weeks. Treatment is now given with multiple-energy linear accelerators, CT-based simulation, 3-dimensional beam modulation for much greater dose homogeneity, on-board imaging for greater daily accuracy, and various techniques to reduce cardiac dose.

Manifestation pattern of early-late vaginal morbidity after definitive radiation (chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: an analysis from the EMBRACE study.

BACKGROUND AND PURPOSE: Brachytherapy in the treatment of locally advanced cervical cancer has changed substantially because of the introduction of combined intracavitary/interstitial applicators and an adaptive target concept, which is the focus of the prospective, multi-institutional EMBRACE study (www.embracestudy.dk) on image-guided adaptive brachytherapy (IGABT). So far, little has been reported about the development of early to late vaginal morbidity in the frame of IGABT. Therefore, the aim of the present EMBRACE analysis was to evaluate the manifestation pattern of vaginal morbidity during the first 2 years of follow-up. METHODS AND MATERIALS: In total, 588 patients with a median follow-up time of 15 months and information on vaginal morbidity were included. Morbidity was prospectively assessed at baseline, every 3 months during the first year, and every 6 months in the second year according to the Common Terminology Criteria for Adverse Events, version 3, regarding vaginal stenosis, dryness, mucositis, bleeding, fistula, and other symptoms. Crude incidence rates, actuarial probabilities, and prevalence rates were analyzed. RESULTS: At 2 years, the actuarial probability of severe vaginal morbidity (grade ≥3) was 3.6%. However, mild and moderate vaginal symptoms were still pronounced (grade ≥1, 89%; grade ≥2, 29%), of which the majority developed within 6 months. Stenosis was most frequently observed, followed by vaginal dryness. Vaginal bleeding and mucositis were mainly mild and infrequently reported. CONCLUSION: Severe vaginal morbidity within the first 2 years after definitive radiation (chemo)therapy including IGABT with intracavitary/interstitial techniques for locally advanced cervical cancer is limited and is significantly less than has been reported from earlier studies. Thus, the new adaptive target concept seems to be a safe treatment with regard to the vagina being an organ at risk. However, mild to moderate vaginal morbidity is still pronounced with currently applied IGABT, and it needs further attention.

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy.

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Focal radiotherapy as focal therapy of prostate cancer.

PURPOSE OF REVIEW: Focal radiotherapy treatment procedures play an increasingly important role in function-preservation and organ-preservation treatment techniques. As an alternative to traditional whole-gland radiotherapy regimes, focal prostate radiotherapy may be of benefit for both primary tumor as well as locally recurrent disease. This is a review of the current literature on the topic, including patient selection, preliminary toxicity, and outcome data as well as a technical overview on treatment delivery techniques. RECENT FINDINGS: Partial organ treatment in early prostate cancer (PCa) is now technically feasible with both newer external-beam and brachytherapy technology. To date, only small and generally monoinstitutional series have been published in the literature. Early feasibility and toxicity data are encouraging, and demonstrate potential advantages for the role of focal brachytherapy in early PCa. Although some advanced external-beam techniques can also be used to deliver focal therapy within the prostate, there is no relevant publication in the literature. SUMMARY: Radiotherapy, especially interventional radiotherapy (brachytherapy), is a technically feasible treatment technique to deliver focal radiotherapy for PCa. To date, only preliminary results are available for all forms of interventional radiotherapy (high dose rate, low dose rate, and pulsed dose rate) for focal PCa treatment and no large cohort comparative results are published. As interventional radiotherapy (brachytherapy) as yet lacks any such long-term studies, comparative outcome data are not available to suggest differences in efficacy for one form of brachytherapy or another.