Mechanisms and protective measures for radiation-induced brachial plexus nerve injury.

Radiation therapy is a common treatment modality for patients with malignant tumors of the head and neck, chest and axilla. However, radiotherapy inevitably causes damage to normal tissues at the irradiated site, among which damage to the brachial plexus nerve(BP) is a serious adverse effect in patients receiving radiation therapy in the scapular or axillary regions, with clinical manifestations including abnormal sensation, neuropathic pain, and dyskinesia, etc. These adverse effects seriously reduce the living quality of patients and pose obstacles to their prognosis. Therefore, it is important to elucidate the mechanism of radiation induced brachial plexus injury (RIBP) which remains unclear. Current studies have shown that the pathways of radiation-induced BP injury can be divided into two categories: direct injury and indirect injury, and the indirect injury is closely related to the inflammatory response, microvascular damage, cytokine production and other factors causing radiation-induced fibrosis. In this review, we summarize the underlying mechanisms of RIBP occurrence and possible effective methods to prevent and treat RIBP.

Hypofractionated Stereotactic Radiation Therapy Dosimetric Tolerances for the Inferior Aspect of the Brachial Plexus: A Systematic Review.

We sought to systematically review and summarize dosimetric factors associated with radiation-induced brachial plexopathy (RIBP) after stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT). From published studies identified from searches of PubMed and Embase databases, data quantifying risks of RIBP after 1- to 10-fraction SBRT/HIGRT were extracted and summarized. Published studies have reported <10% risks of RIBP with maximum doses (Dmax) to the inferior aspect of the brachial plexus of 32 Gy in 5 fractions and 25 Gy in 3 fractions. For 10-fraction HIGRT, risks of RIBP appear to be low with Dmax < 40 to 50 Gy. For a given dose value, greater risks are anticipated with point volume-based metrics (ie, D0.03-0.035cc: minimum dose to hottest 0.03-0.035 cc) versus Dmax. With SBRT/HIGRT, there were insufficient published data to predict risks of RIBP relative to brachial plexus dose-volume exposure. Minimizing maximum doses and possibly volume exposure of the brachial plexus can reduce risks of RIBP after SBRT/HIGRT. Further study is needed to better understand the effect of volume exposure on the brachial plexus and whether there are location-specific susceptibilities along or within the brachial plexus structure.

Brachial Plexus Tolerance to Single-Session SABR in a Pig Model.

PURPOSE: The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. METHODS AND MATERIALS: Ten Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiotherapy. A 2.5-cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in 3 groups with prescription doses of 16 (n = 3), 19 (n = 4), and 22 Gy (n = 3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. RESULTS: Seven of the 10 pigs developed motor deficit to the front limb of the irradiated side, with a latency from 5 to 8 weeks after irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3 Gy for neurologic deficit, but the number of animals was insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6 Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histologic lesions to the left-sided plexus consistent with radiation-induced neuropathy. CONCLUSIONS: The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5-cm length of the brachial plexus cords was determined to be 19.3 Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.

Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience.

BACKGROUND: Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. METHODS: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. RESULTS: This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3-4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3-4 fractions. CONCLUSIONS: This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

Mid-position treatment strategy for locally advanced lung cancer: a dosimetric study.

OBJECTIVE: The internal target volume (ITV) strategy generates larger planning target volumes (PTVs) in locally advanced non-small cell lung cancer (LA-NSCLC) than the Mid-position (Mid-p) strategy. We investigated the benefit of the Mid-p strategy regarding PTV reduction and dose to the organs at risk (OARs). METHODS: 44 patients with LA-NSCLC were included in a randomized clinical study to compare ITV and Mid-p strategies. GTV were delineated by a physician on maximum intensity projection images and on Mid-p images from four-dimensional CTs. CTVs were obtained by adding 6 mm uniform margin for microscopic extension. CTV to PTV margins were calculated using the van Herk's recipe for setup and delineation errors. For the Mid-p strategy, the mean target motion amplitude was added as a random error. For both strategies, three-dimensional conformal plans delivering 60-66 Gy to PTV were performed. PTVs, dose-volume parameters for OARs (lung, esophagus, heart, spinal cord) were reported and compared. RESULTS: With the Mid-p strategy, the median of volume reduction was 23.5 cm3 (p = 0.012) and 8.8 cm3 (p = 0.0083) for PTVT and PTVN respectively; the median mean lung dose reduction was 0.51 Gy (p = 0.0057). For 37.1% of the patients, delineation errors led to smaller PTV with the ITV strategy than with the Mid-p strategy. CONCLUSION: PTV and mean lung dose were significantly reduced using the Mid-p strategy. Delineation uncertainty can unfavorably impact the advantage. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first dosimetric comparison study between ITV and Mid-p strategies for LA-NSCLC.

Axillary nodal irradiation practice in the sentinel lymph node biopsy era: Comparison of the contemporary available 3D and IMRT techniques.

OBJECTIVE: Our study aimed to compare regional node coverage and doses to the organ at risk (OAR) using conventional technique (CT) vs "AMAROS" (AT) vs intensity-modulated radiation therapy (IMRT) techniques in patients receiving regional nodal irradiation (RNI) for breast cancer (BC). METHODS: We included 30 consecutive patients with BC who received RNI including axillary nodes. Two independent and blinded dosimetric RNI plans were generated for all patients. For target volume coverage, we analyzed the V95%, the D95%, the mean and the minimal dose within the nodal station. For hotspots within nodal target volume, we used the V105%, the V108% and the maximal doses. For OAR, lung V20, mean lung and heart doses, the maximal dose to the brachial plexus and the axillary-lateral thoracic vessel junction region were compared between the three techniques. RESULTS: Target volume coverage and hotspots: Mean V95% in stations I, II, III and IV were 35.8% and 75% respectively with CV, 22.59 and 59.9% respectively with AT technique and 45.58 and 99.6% respectively with IMRT with statistically significant differences (p < 0.001). Mean V105% (cc) in axillary and supraclavicular stations were 21.3 and 6.4 respectively with CV, 1.2 and 0.02 respectively with AT technique and 0.5 and 0.4 respectively with IMRT with statistically significant differences (p < 0.001)..OARs: The mean ipsilateral lung V20 was 16.9%, 16.4 and 13.3% with CT, AT and IMRT respectively. The mean heart dose (Gy) was 0.3, 0.2 and 0.2 with CT, AT and IMRT respectively. The maximal dose to the plexus brachial (Gy) was 50.3, 46.3 and 47.3 with CT, AT and IMRT respectively. The maximal dose to the axillary-lateral thoracic vessel junction (Gy) was 52.3, 47.3 and 47.6 with CT, AT and IMRT respectively. The differences were statistically significant for all OAR (p < 0.001). CONCLUSION: AT is a valuable technique for RNI including axilla in patients with limited sentinel lymph node biopsy involvement without additional axillary lymph node dissection since it decreases hotspots in the target volume and lowers the radiation exposure of the OAR. For more advanced tumors or patients who did not respond to primary systemic therapy, CT or IMRT should be considered because of their better coverage of the potentially residual nodal disease. IMRT combines several advantages of offering high conformal plans, limited hotspots and protection of main OAR. The clinical impact of these dosimetric differences need to be addressed. ADVANCES IN KNOWLEDGE: This study is to our knowledge the first to compare conventional three-dimensional and IMRT techniques for regional nodal irradiation for each nodal station in breast cancer in a context of increasing utilization of axillary irradiation.

Dosimetric analysis and clinical outcomes of brachial plexus as an organ-at-risk in head-and-neck cancer patients treated with intensity-modulated radiotherapy.

OBJECTIVES: To document the dose received by brachial plexus (BP) in patients treated with intensity-modulated radiotherapy (IMRT) for head-and-neck squamous cell carcinoma (HNSCC) and report the incidence of brachial plexopathy. METHODS: Newly diagnosed patients of HNSCC treated with radical or adjuvant IMRT were included in this retrospective study. No dosimetric constraints were applied for BP maximum dose equivalent dose (EQD2 α/ß = 3). Patients with minimum 6-month follow-up were included and patients with suspicion of plexopathy were evaluated further. RESULTS: Sixty-seven patients were eligible and 127 BP were analyzed. The mean BP maximum dose (BPmax) was 62.4 Gy (+6.9), while mean BP volume was 28.1 cc (+4.1). Proportion of patients receiving BPmax >66 and >70 Gy were 34.7% and 14.2%. The mean BPmax for T4 tumors was significantly higher than T1 tumors (65 vs. 57.5 Gy, P = 0.005) but when adjusted for N-category, T-category was not independently significant in accounting for BPmax >66 or >70 Gy. Mean BPmax for N0 versus N2+ was 59.8 versus 65.6 Gy (P = 0.0001) and N1 versus N2+ was 61.6 versus 65.6 Gy (P = 0.018). After adjusting for T-category, patients with N2+ had a mean 4.2 Gy higher BPmax than N0-N1 (P = 0.0001). Stage III-IV patients had a mean six Gy higher BPmax doses than Stage I-II disease (P = 0.0001). With a median follow-up of 28 months (interquartile range 16-42), no patient had brachial plexopathy. CONCLUSION: Clinically significant plexopathy was not seen in spite of majority having over 2-years follow-up and a third of patients having dose above the recommended tolerance. Only nodal category independently influenced dose to the brachial plexii.

Radiation-induced brachial plexus toxicity after SBRT of apically located lung lesions.

Purpose: To evaluate the rate and dose response of brachial plexus toxicity post stereotactic body radiation therapy (SBRT) of apically situated lung lesions. Material/methods: We retrospectively identified all patients with apically located tumors, defined by the epicenter of the tumor being located superiorly to the aortic arch, and treated with SBRT between 2008 and 2013. Patients with a shorter follow-up than 6 months were excluded. Primary aim was to evaluate radiation-induced brachial plexopathy (RIBP). Dose to the plexus was assessed by a retrospective delineation of the brachial plexus on the CT used for treatment planning. Then, Dmax, D0.1cc, D1cc and D3.0cc of the brachial plexus were collected from the dose-volume histograms (DVH) and recalculated to the biologically effective dose (BED) using α/ß = 3 Gy. A normal tissue complication probability (NTCP) model, based on four different dose-volume parameters (BED3,max, BED3,0.1cc, BED3,1.0cc, BED3,3.0cc) was fitted to the data. Results: Fifty-two patients with 56 apically located tumors were identified. Median prescription dose per fraction was 15 Gy (range 6-17) and median number of fractions was 3 (3-10). With a median follow-up of 30 months (6.1-72) seven patients experienced maximum grade 2 (scored 3 times) or 3 (scored 4 times) RIBP after a median of 8.7 months (range 4.0-31). Three patients had combined symptoms with pain, sensory and motor affection and four patients had isolated pain. Median BED3,max for the patients experiencing RIBP was 381 Gy (range 30-524) versus BED3,max of 34 Gy (range 0.10-483) for the patients without RIBP. The NTCP models showed a very high predictive ability (area under the receiver operating characteristic curve (AUC) 0.80-0.88). Conclusion: SBRT of apically located lung lesions may cause severe neurological symptoms; for a three-fraction treatment, we suggest that the maximum dose to the plexus should be kept ≤30 Gy (130 Gy BED3).

A dosimetric evaluation on applying RTOG-based and CT/MRI-based delineation methods to brachial plexus in radiotherapy of nasopharyngeal carcinoma treated with helical tomotherapy.

OBJECTIVE: In radiotherapy of nasopharyngeal carcinoma (NPC) patients, the brachial plexus (BP) situated at both sides of the neck is often irradiated to high dose. This study was to evaluate different BP delineation methods and analyse the dosimetric consequences when applying BP dose constraints in radiotherapy planning of NPC. METHODS: 15 NPC cases radically treated with helical tomotherapy were recruited. Apart from the original treatment plan (Plan A), two new plans (Plans B and C) with additional BP dose constraints were computed using the same planning CT images, structures and planning parameters. Plan B consisted of BP contours based on Radiation Therapy Oncology Group (RTOG)-endorsed atlas; while those in Plan C were based on MR images registered with the planning CT images. RESULTS: The mean BP volume by RTOG method was 19.04 ± 3.50 cm3 vs 10.44 ± 2.00 cm3 by CT/MRI method. The mean BP overlapping volume between the two contouring methods was 1.9 cm3 (0.38-4.03 cm3). There was significant difference between two methods (p < 0.001). The average Dmax, Dmean, D5%, D10% and D15% of both sides of BP in Plan A were significantly higher than those in both Plan B and Plan C. There were no significant dose differences in the targets and organs at risk (OARs) after applying dose constraints in Plan B and Plan C. CONCLUSION: RTOG method was recommended since larger BP volume provided better protection. Applying BP dose constraints during tomotherapy plan optimisation for NPC patients could significantly reduce the BP dose (p < 0.05) without compromising the doses to the targets and other OARs. ADVANCES IN KNOWLEDGE: This is the first study comparing the delineation method based on RTOG-endorsed atlas with the conventional CT/MRI delineation method for BP in tomotherapy of NPC patients. Our results showed that BP dose could be significantly reduced after applying the dose constraints without compromising the doses to the target volumes and other OARs. The RTOG method was more favoured as it gave a relatively larger BP volume and therefore offered better organ sparing.

Different radiation techniques to deliver therapeutic dose to the axilla in patients with sentinel lymph node-positive breast cancer: Doses, techniques challenges and clinical considerations.

PURPOSE: To evaluate the coverage of different levels of axillary lymph nodes and organs at risk according to the field design of AMAROS study (levels I-II-III-IV), breast tangents with supraclavicular and infraclavicular fields (levels II-III-IV) and high tangent fields to the breast after breast-conserving surgery. MATERIALS AND METHODS: We delineated the axillary lymph nodes levels I-IV in 34 patients treated with breast-conserving surgery and sentinel lymph nodes biopsy. Field design according to AMAROS study - levels I-IV in patients without axillary dissection - as well as irradiation of levels II-IV used in N+ patients after axillary dissection, and also high tangent fields was simulated. Mean dose levels and volumes covered by 95% or 80% isodoses were evaluated. Doses to ipsilateral lung, heart and brachial plexus were compared. Paired t test was used. RESULTS: AMAROS study and levels II-IV plans delivered therapeutic dose to high axilla (levels II-IV), but the high tangent fields showed inefficacy to cover these volumes, P<0.001). In terms of organs at risk, especially, ipsilateral lung, AMAROS study plan was found to significantly increase the volume receiving at least 10Gy (I-IV:46.8%, II-IV: 39%), but also the volume receiving at least 20Gy (I-IV: 39.3%, II-IV: 31.3%), and V30Gy (I-IV: 34.2% vs II-IV: 26.1%), as well as the mean dose (I-IV: 18.6Gy, II-IV: 15.2Gy, P<0.001). CONCLUSIONS: The omission of axillary dissection and the axilla irradiation need is associated with high dose irradiation of the lungs, and with higher toxicity. The indication of axillary dissection or irradiation of low axilla could be individualized in relation with individual comorbidities and factors of risk.

Contouring workload in adjuvant breast cancer radiotherapy.

PURPOSE: To measure the impact of contouring on worktime in the adjuvant radiation treatment of breast cancer, and to identify factors that might affect the measurements. MATERIAL AND METHODS: The dates and times of contouring clinical target volumes and organs at risk were recorded by a senior and by two junior radiation oncologists. Outcome measurements were contour times and the time from start to approval. The factors evaluated were patient age, type of surgery, radiation targets and setup, operator, planning station, part of the day and day of the week on which the contouring started. The Welch test was used to comparatively assess the measurements. RESULTS: Two hundred and three cases were included in the analysis. The mean contour time per patient was 34minutes for a mean of 4.72 structures, with a mean of 7.1minutes per structure. The clinical target volume and organs at risk times did not differ significantly. The mean time from start to approval per patient was 29.4hours. Factors significantly associated with longer contour times were breast-conserving surgery (P=0.026), prone setup (P=0.002), junior operator (P<0.0001), Pinnacle planning station (P=0.026), contouring start in the morning (P=0.001), and contouring start by the end of the week (P<0.0001). Factors significantly associated with time from start to approval were age (P=0.038), junior operator (P<0.0001), planning station (P=0.016), and contouring start by the end of the week (P=0.004). CONCLUSION: Contouring is a time-consuming process. Each delineated structure influences worktime, and many factors may be targeted for optimization of the workflow. These preliminary data will serve as basis for future prospective studies to determine how to establish a cost-effective solution.

Management of Radiation Toxicity in Head and Neck Cancers.

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.

Utilidad de la monitorización electrofisiológica transoperatoria en el abordaje de las lesiones de plexo braquial / Usefulness of transoperative electrophysiological monitoring in the treatment of brachial plexus injuries

Antecedentes y Objetivo. Las lesiones del plexo braquial son devastadoras para los pacientes. La baja especificidad y el valor predictivo positivo en los estudios de electrofisiología prequirúrgicos son la principal indicación para la realización de una monitorización electrofiológica intraoperatoria. A pesar de los grandes avances logrados, los resultados del tratamiento quirúrgico en los pacientes con lesión de plexo braquial están lejos de un panorama ideal. Sin embargo, la terapia quirúrgica actual logra mejores resultados que los tratamientos sin reconstrucción nerviosa. El objetivo de este trabajo es analizar los resultados postquirúrgicos de los pacientes sometidos a cirugía de plexo braquial con y sin monitorización electrofiosológica transoperatoria. Material y Método. Evaluamos los expedientes y videos pre y postoperatorios de nuestros pacientes con lesión de plexo braquial entre 2007 y 2014 sometidos a neurolisis, injertos nerviosos y/o transferencias nerviosas. Excluimos a los pacientes con transferencias musculares o artrodesis, y divididos el total en 2 grupos dependiendo de la realización o no de monitorización electrofiológica transoperatoria. Analizamos los videos mediante una escala de evaluación basada en la tabla de valoración de Narakas y Raimondi. Resultados. Obtuvimos 25 pacientes. Todas las evaluaciones postquirúrgicas presentaron mejoría (p <0.05) independientemente de la realización o no de monitorización electrofisiológica transoperatoria. La evaluación postquirúrgica con monitorización transoperatoria de la rotación externa del hombro y el movimiento de los dedos centrales obtuvieron mejoría (p <0.05), en comparación con aquellos en los que no se realizó monitorización. En la evaluación postquirúrgica, 53.3% de los pacientes con monitorización presentó ascenso en 1 o más de los rangos de la escala; mientras que en los pacientes sin monitorización solo el 20% presentó incremento. Ninguno presentó menor puntaje en la evaluación postquirúrgica con respecto a la preoperatoria. Conclusiones. A pesar de no lograr reestablecer la función del miembro afectado, todos los pacientes presentaron mejoría clínica en el periodo postoperatorio. Cabe resaltar que los pacientes con monitorización electrofisiológica transoperatoria obtuvieron mejores resultados clínicos en el periodo postquirúrgico (AU)

Background and Objective. Brachial plexus injuries are one of the most devastating lesions for the patient. The presurgical low specificity and positive predicted value in the electrophysiology studies are the main indication to perform an intraoperative nerve recording. Despite the great progress obtained, the surgical treatment results in patients with brachial plexus lesions are fare from an ideal scenario. Nevertheless, the surgical management obtains better results than nonsurgical treatment. The aim of this study is to analyze the postoperative results of patients with brachial plexus surgery with and without transoperative electrophysiological monitoring. Methods. From 2007 to 2014 medical files and preoperative and postoperative videos of our patients with brachial plexus injury were evaluated, those patients underwent neurolysis, nerve grafts and/or nerve transfer. Patients with muscle transfer or arthrodesis were excluded. Two groups were formed, depending on the performance or absence of intraoperative nerve recording. Their pre and post-surgery videos were reviewed and rated according to a scale based on the Narakas and Raimondi valuation. Results. Twenty five patients were obtained. All postoperative assessments showed a statistically significant improvement (p <0.05) regardless either of the presence or the absence of intraoperative nerve recording. During the postoperative evaluation of the group with intraoperative monitoring, shoulder external rotation and movement of the middle fingers obtained statistically significant improvement (p <0.05), in comparison to the group without nerve recording. In the postoperative evaluation, 53.3% of patients presented with intraoperative nerve recording arose in 1 or more of the ranges of the rating scale; whereas in patients without it only 20% had increased. None of the patients gave a lower score while postoperative assessment. Conclusions. Even though the surgical treatment did not reestablish the complete patient movement, it reached better postsurgical outcomes. Draws attention to intraoperative nerve monitoring studies provide better clinical outcomes in the postoperative period in patients with brachial plexus inju (AU)

Tolerance of the Brachial Plexus to High-Dose Reirradiation.

PURPOSE: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. METHODS AND MATERIALS: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). RESULTS: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus-related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). CONCLUSION: The development of brachial plexus-related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.

[Intensity-modulated radiotherapy of head and neck cancers. Dose constraint for spinal cord and brachial plexus]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures. Dose de tolérance des tissus sains : moelle épinière et plexus brachial.

Given the ballistic opportunities it offers, intensity-modulated radiotherapy has emerged as the gold standard treatment for head and neck cancers. Protection of organs at risk is one of the objectives of optimization during the planning process. The compliance of dose constraints to the nervous system must be prioritized over all others. To avoid complications, it is recommended to respect a maximum dose of 50Gy to the spinal cord, and 60Gy to the brachial plexus using conventional fractionation of 2Gy per fraction. These constraints can be adapted depending on the clinical situation; they will probably be refocused by the follow-up of the IMRT studies.

Normal tissue considerations and dose-volume constraints in the moderately hypofractionated treatment of non-small cell lung cancer.

Hypofractionated radiation therapy (RT) regimes in non-small cell lung cancer (NSCLC) have become increasingly popular with a number of international trials currently underway. The majority of the dose-volume-constraints (DVCs) published in the literature refer to conventional 2Gy per fraction deliveries. Here relevant organs-at-risk (OARs) are identified and available dose-volume constraint data discussed and summarised for moderately hypofractionated NSCLC regimes. The OARs examined include lung, brachial plexus, heart, oesophagus, airway and spinal cord. Where available the toxicity rates are also reported with all data summarised tabulated to aid its use in the clinic.

Optimal number of atlases and label fusion for automatic multi-atlas-based brachial plexus contouring in radiotherapy treatment planning.

BACKGROUND: The present study aimed to define the optimal number of atlases for automatic multi-atlas-based brachial plexus (BP) segmentation and to compare Simultaneous Truth and Performance Level Estimation (STAPLE) label fusion with Patch label fusion using the ADMIRE® software. The accuracy of the autosegmentations was measured by comparing all of the generated autosegmentations with the anatomically validated gold standard segmentations that were developed using cadavers. MATERIALS AND METHODS: Twelve cadaver computed tomography (CT) atlases were used for automatic multi-atlas-based segmentation. To determine the optimal number of atlases, one atlas was selected as a patient and the 11 remaining atlases were registered onto this patient using a deformable image registration algorithm. Next, label fusion was performed by using every possible combination of 2 to 11 atlases, once using STAPLE and once using Patch. This procedure was repeated for every atlas as a patient. The similarity of the generated automatic BP segmentations and the gold standard segmentation was measured by calculating the average Dice similarity (DSC), Jaccard (JI) and True positive rate (TPR) for each number of atlases. These similarity indices were compared for the different number of atlases using an equivalence trial and for the two label fusion groups using an independent sample-t test. RESULTS: DSC's and JI's were highest when using nine atlases with both STAPLE (average DSC = 0,532; JI = 0,369) and Patch (average DSC = 0,530; JI = 0,370). When comparing both label fusion algorithms using 9 atlases for both, DSC and JI values were not significantly different. However, significantly higher TPR values were achieved in favour of STAPLE (p < 0,001). When fewer than four atlases were used, STAPLE produced significantly lower DSC, JI and TPR values than did Patch (p = 0,0048). CONCLUSIONS: Using 9 atlases with STAPLE label fusion resulted in the most accurate BP autosegmentations (average DSC = 0,532; JI = 0,369 and TPR = 0,760). Only when using fewer than four atlases did the Patch label fusion results in a significantly more accurate autosegmentation than STAPLE.

Brachial plexus dose tolerance in head and neck cancer patients treated with sequential intensity modulated radiation therapy.

PURPOSE: We aimed to study the radiation induced brachial plexopathy in patients with head and neck squamous cell carcinoma (HNSCC) treated with Sequential Intensity Modulated Radiation Therapy (S-IMRT). METHODS AND MATERIALS: This IRB approved study included 68 patients with HNSCC treated consecutively. Detailed dose volume histogram data was generated for ipsilateral and contralateral brachial plexus (BP) volumes receiving a specified dose (Vds) i.e. V50-V75 and dose in Gray covering specified percent of BP volume (Dvs) i.e. D5-D30 and maximum point doses (Dmax). To assess BP injury all patients' charts were reviewed in detail for sign and symptoms of BP damage. Post-hoc comparisons were done using Tukey-Kramer method to account for multiple significance testing. RESULTS: The mean and maximum doses to BP were significantly different (p < .05) based on tumor site, nodal status and tumor stage. The mean volume to the ipsilateral BP for V50, V60, V70, and V75 were 7.01 cc, 4.37 cc, 1.47 cc and 0.24 cc, respectively. The mean dose delivered to ≤5% of ipsilateral BP was 68.70 Gy (median 69.5Gy). None of the patients had acute or late brachial plexopathy or any other significant neurological complications, with a minimum follow up of two years (mean 54 months). CONCLUSIONS: In this study cohort, at a minimum of two-years follow up, the mean dose of 68.7Gy, a median dose to 69.5Gy to ≤5% of ipsilateral BP, and a median Dmax of 72.96Gy did not result in BP injury when patients were treated with S-IMRT technique. However, longer follow up is needed.