Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma.

BACKGROUND: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. METHODS: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. RESULTS: The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. CONCLUSION: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.

Repeat reirradiation of the spinal cord: multi-national expert treatment recommendations.

BACKGROUND: Improved survival of patients with spinal bone metastases has resulted in an increased number of referrals for retreatment and repeat reirradiation. METHODS: A consortium of expert radiation oncologists (RO) has been established with the aim of providing treatment recommendations for challenging clinical scenarios for which there are no established guidelines. In this case, a patient developed local progression of a T5 vertebral lesion after two prior courses of palliative radiotherapy (time interval >12 months, assumed cumulative biologically equivalent dose in 2­Gy fractions [EQD2] for spinal cord [alpha/beta 2 Gy] 75 Gy). Expert recommendations were tabulated with the aim of providing guidance. RESULTS: Five of seven RO would offer a third course of radiotherapy, preferably with advanced techniques such as stereotactic radiotherapy. However, the dose-fractionation concepts were heterogeneous (3-20 fractions) and sometimes adjusted to different options for systemic treatment. All five RO would compromise target volume coverage to reduce the dose to the spinal cord. Definition of the spinal cord planning-organ-at-risk volume was heterogeneous. All five RO limited the EQD2 for spinal cord. Two were willing to accept more than 12.5 Gy and the highest EQD2 was 19 Gy. CONCLUSIONS: The increasing body of literature about bone metastases and spinal cord reirradiation has encouraged some expert RO to offer palliative reirradiation with cumulative cord doses above 75 Gy EQD2; however, no consensus was achieved. Strategies for harmonization of clinical practice and development of evidence-based dose constraints are discussed.

Intraoperative radiation exposure in spinal scoliosis surgery for pediatric patients using the O-arm® imaging system.

PURPOSE: The O-arm® navigation system allows intraoperative CT imaging that can facilitate highly accurate instrumentation surgery, but radiation exposure is higher than with X-ray radiography. This is a particular concern in pediatric surgery. The purpose of this study is to examine intraoperative radiation exposure in pediatric spinal scoliosis surgery using O-arm. METHODS: The subjects were 38 consecutive patients (mean age 12.9 years, range 10-17) with scoliosis who underwent spinal surgery with posterior instrumentation using O-arm. The mean number of fused vertebral levels was 11.0 (6-15). O-arm was performed before and after screw insertion, using an original protocol for the cervical, thoracic, and lumbar spine doses. RESULTS: The average scanning range was 6.9 (5-9) intervertebral levels per scan, with 2-7 scans per patient (mean 4.0 scans). Using O-arm, the dose per scan was 92.5 (44-130) mGy, and the mean total dose was 401 (170-826) mGy. This dose was 80.2% of the mean preoperative CT dose of 460 (231-736) mGy (P = 0.11). The total exposure dose and number of scans using intraoperative O-arm correlated strongly and significantly with the number of fused levels; however, there was no correlation with the patient's height. CONCLUSIONS: As the fused range became wider, several scans were required for O-arm, and the total radiation exposure became roughly the same as that in preoperative CT. Use of O-arm in our original protocol can contribute to reduction in radiation exposure.

Radiation-induced camptocormia and dropped head syndrome: Review and case report of radiation-induced movement disorders.

BACKGROUND: In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a "chin to chest position." Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. METHODS: A PubMed search with the keywords "camptocormia," "dropped head syndrome," "radiation-induced myopathy," "radiation-induced neuropathy," and "radiation-induced movement disorder" was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. RESULTS: In total, nine case series of radiation-induced DHS (n = 45 patients) and-including our case-three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. CONCLUSION: The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable.

Clinical curative effect of percutaneous vertebroplasty combined with 125I-seed implantation in treating spinal metastatic tumor.

This paper selected and studied 15 in-hospital patients to analyze and discuss the clinical curative effect of percutaneous vertebroplasty (PVP) combined with (125)I-seed implantation in treating spinal metastatic tumor. The evaluation of clinical curative effects was based on the observation of several factors, namely recovery conditions of vertebral body's leading edge and middle section before and after surgery, improvements of kyphosis Cobb angle, visual analog scale (VAS), and Barthel Index (BI). The paper found significant difference between preoperative VAS and postoperative VAS, and the same situation occurred to BI. However, compared to the loss rate of vertebral body's leading edge and middle section and the improvement of Cobb angle before operative, postoperative loss rate and Cobb angle did not show statistical difference. Thus the conclusion is that PVP combined with (125)I-seed implantation is a minimally invasive surgery for effectively treating spinal metastatic tumor, which does well in rapidly releasing pains, improving patients' daily life activities and life qualities.

Stability of spinal bone metastases in breast cancer after radiotherapy: a retrospective analysis of 157 cases.

PURPOSE: This retrospective analysis was performed to evaluate osteolytic bone lesions of breast cancer in the thoracic and lumbar spine after radiotherapy (RT) in terms of stability using a validated scoring system. METHODS: The stability of 157 osteolytic metastases, treated from January 2000 to January 2012, in 115 patients with breast cancer was evaluated retrospectively using the Taneichi score. Predictive factors for stability were analyzed and survival rates were calculated. RESULTS: Eighty-five (54%) lesions were classified as unstable prior to RT. After 3 and 6 months, 109 (70%) and 124 (79%) lesions, respectively, were classified as stable. Thirty fractures were detected prior to RT, and after RT seven cases (4.5%) with pathologic fractures were found within 6 months. None of the examined predictive factors showed significant correlation with stability 6 months after RT. After a median follow-up of 16.7 months, Kaplan-Meier estimates revealed an overall survival of 83% after 5 years. CONCLUSION: The majority of patients showed an improved or unchanged stability of the involved vertebral bodies after 6 months. The patients showed only minor cancer-related morbidity during follow-up and reached comparably high survival rates.

Early onset recall pneumonitis during targeted therapy with sunitinib.

BACKGROUND: Sunitinib interacts with radiation therapy, leading to synergism of the toxicities of these treatments. Radiation recall pneumonitis is a rare but serious complication of targeted therapy with tyrosine kinase inhibitors. CASE PRESENTATION: The case of a patient with metastatic renal cell cancer (RCC) who developed recall pneumonitis on the first cycle of systemic sunitinib treatment is reported here. A 65-year-old man with RCC and bone metastasis underwent radiation therapy on his thoracic vertebrae (Th5-8) with a total dose of 24 Gy. Sunitinib (37.5 mg) was started 14 days after completing the radiation therapy. On the 14th day of sunitinib treatment, the patient developed progressive fever with worsening of dyspnea and general weakness. Treatment with pulse administration of prednisolone 1,000 mg for 3 days was initiated. Thereafter, the symptoms and the radiological findings regarding the interstitial filtration gradually improved over 7 days. CONCLUSION: To our knowledge, this is the first report of early onset recall pneumonitis during sunitinib therapy. At present, how sunitinib interacts with radiation therapy remains unclear. The possibility that tyrosine kinase inhibitor therapy, including with sunitinib, after radiation therapy may lead to adverse effects should be kept in mind.

Prognostic factors in a series of 504 breast cancer patients with metastatic spinal cord compression.

BACKGROUND: This study was performed to identify new significant prognostic factors in breast cancer patients irradiated for metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: The data of 504 patients with breast cancer patients with MSCC were retrospectively analyzed with respect to posttreatment motor function, local control of MSCC, and survival. The investigated potential prognostic factors included age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, other bone metastases, visceral metastases, pretreatment ambulatory status, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits before radiotherapy, and the radiation schedule. RESULTS: On multivariate analysis, better functional outcome was associated with ambulatory status prior to RT (estimate - 1.29, p < 0.001), no visceral metastases (estimate - 0.52, p = 0.020), and slower development of motor deficits (estimate + 2.47, p < 0.001). Improved local control was significantly associated with no other bone metastases (risk ratio (RR) 4.33, 95% confidence interval (CI) 1.36-14.02, p = 0.013) and no visceral metastases (RR 3.02, 95% CI 1.42-6.40, p = 0.005). Improved survival was significantly associated with involvement of only 1-2 vertebrae (RR 1.27, 95% CI 1.01-1.60, p = 0.044), ambulatory status before radiotherapy (RR 1.75, 95% CI 1.23-2.50, p = 0.002), no other bone metastases (RR 1.93, 95% CI 1.18-3.13, p = 0.009), no visceral metastases (RR 7.60, 95% CI 5.39-10.84, p < 0.001), and time developing motor deficits before radiotherapy (RR 1.55, 95% CI 1.30-1.86, p < 0.001). CONCLUSION: Several new independent prognostic factors were identified for treatment outcomes. These prognostic factors should be considered in future trials and may be used to develop prognostic scores for breast cancer patients with MSCC.

CT-myelography for high-dose irradiation of spinal and paraspinal tumors with helical tomotherapy: revival of an old tool.

BACKGROUND AND PURPOSE: High-dose irradiation or reirradiation of spinal and paraspinal tumors is a challenge particularly in the presence of metal artifacts after surgery. Image-guided advanced intensity-modulated radiotherapy delivers high-dose radiation to the tumor sparing the spinal cord. Precise delineation of the spinal cord is necessary treating para- and intraspinal tumors with a sufficient dose. PATIENTS AND METHODS: The use of myelo-CT was evaluated in 23 patients with spinal and paraspinal tumors. All patients had had previous surgery with metal implants in the radiation area. All patients had an indication for high-dose irradiation. Treatment planning was performed using nonenhanced and contrast-enhanced myelo-CT in the same position and immobilization and both CT scans were matched. Treatment was performed by using a tomotherapy treatment unit. RESULTS: Contouring of the myelon in all slices of the myelo-CT was possible in 20 of 23 patients. All these patients were treated with doses of median 69.4 Gy in 2 Gy/1.8 Gy single doses using daily image guidance. One patient received an integrated boost with a TD/SD of 70/2.3 Gy. No side effects have been observed so far during a median follow-up of 15.5 months. No separation between tumor and myelon could be observed in 3 patients. CONCLUSION: Myelo-CT offers a distinct delineation of the myelon and the paraspinal tumor in case of artifacts due to metal implants after surgery. Using this tool in combination with advanced image guidance and IMRT techniques, patients with relatively radioresistent paraspinal tumors might have the chance of improved local control using higher target doses.

Analysis of local setup errors of sub-regions in cone-beam CT-guided post-mastectomy radiation therapy.

The purpose of the study was to quantify local setup errors and evaluate the planning target volume (PTV) margins for sub-regions in cone-beam computed tomography (CBCT)-guided post-mastectomy radiation therapy (PMRT). The local setup errors of 20 patients undergoing CBCT-guided PMRT were analysed retrospectively. Image registration between CBCT and planning CT was performed using four sub-regions of interest (ROIs): the supraclavicular area (SROI), ipsilateral chest wall region (CROI), ipsilateral chest wall plus supraclavicular region (SROI + CROI) and vertebral region (TROI). Bland-Altman analysis, correlation, local setup errors and PTV margins among these ROIs were evaluated. There was no significant consistency or correlation for registration results between the TROI and the CROI or SROI regions on any translational axis. When using the SROI + CROI as the ROI, the systematic error (Σ) and random error (σ) of the local setup errors for the CROI region were 1.81, 1.19 and 1.76 mm and 1.84, 2.64 and 3.00 mm along the medial-lateral (ML), superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The PTV margins for the CROI region were 5.80, 4.82 and 6.50 mm. The Σ and σ of the local setup errors for the SROI region were 1.29, 1.15 and 0.77 mm and 1.96, 2.65 and 2.2 mm, respectively, and the PTV margins were 4.59, 4.73 and 3.47 mm. Large setup errors and local setup errors occur in PMRT. The vertebral body should not be a position surrogate for the supraclavicular region or chest wall. To compensate for the local setup errors, different PTV margins are required, even with CBCT guidance.

Association of Chemoradiotherapy With Thoracic Vertebral Fractures in Patients With Esophageal Cancer.

Importance: The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown. Objective: To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer. Design, Setting, and Participants: This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020. Exposures: Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group). Main Outcomes and Measures: The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated. Results: A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009). Conclusions and Relevance: This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.

Multimodality image guided total marrow irradiation and verification of the dose delivered to the lung, PTV, and thoracic bone in a patient: a case study.

This work reports our initial experience using multimodality image guidance to improve total marrow irradiation (TMI) using helical tomotherapy. We also monitored the details of the treatment delivery to glean information necessary for the implementation of future adaptive processes. A patient with metastatic Ewing's sarcoma underwent MRI, and bone scan imaging prior to TMI. A whole body kilovoltage CT (kVCT) scan was obtained for intensity modulated TMI treatment planning, including a boost treatment to areas of bony involvement. The delivered dose was estimated by using MVCT images from the helical tomotherapy treatment unit, compared to the expected dose distributions mapped onto the kVCT images. Clinical concerns regarding patient treatment and dosimetric uncertainties were also evaluated. A small fraction of thoracic bone volume received lower radiation dose than the prescribed dose. Reconstructed planned treatment volume (PTV) and the dose delivered to the lung were identical to planned dose. Bone scan imaging had a higher sensitivity for detecting skeletal metastasis compared to MR imaging. However the bone scan lacked sufficient specificity in three dimensions to be useful for planning conformal radiation boost treatments. Inclusion of appropriate imaging modalities improves detection of metastases, which allows the possibility of a radiation dose boost to metastases during TMI. Conformal intensity modulated radiation therapy via helical tomotherapy permitted radiation delivery to metastases in the skull with reduced dose to brain in conjunction with TMI. While TMI reduces irradiation to the lungs, onboard megavoltage computed tomography (MVCT) to verify accurate volumetric dose coverage to marrow-containing thoracic bones may be essential for successful conformal TMI treatment.

PATIENT DOSES IN COMMON DIAGNOSTIC X-RAY EXAMINATIONS.

A local survey was conducted, to evaluate the radiation dose to adult patients who underwent diagnostic X-ray examinations. Patient-related and technical data were recorded, in 1504 patients, for each of the 11 individual projections, of the 7 most common examinations performed in an X-ray room, with 1 digital radiography system. The patient entrance surface air kerma (ESAK) and the effective dose (ED) were calculated based on the X-ray tube output and the exposure parameters, as well as utilisation of suitable conversion coefficients, respectively. The 75th percentiles of the distribution of the ESAK and kerma area product (KAP) values were also established. The mean, median and 75th percentiles were compared with the national reference levels and the most common values reported at the European level through the DOSE DATAMED II project. The corresponding ED values were also compared with the average values reported for all European countries. The mean ESAK, KAP and ED values along with the uncertainty U values for chest PA, chest LAT, cranium AP, cranium LAT, cervical spine AP, cervical spine LAT, lumbar spine AP, lumbar spine LAT, pelvis AP, abdomen AP, kidneys and urinary bladder (KUB) AP were 0.12 (0.001) mGy, 0.66 (0.023) mGy, 1.01 (0.034) mGy, 0.69 (0.098) mGy, 0.72 (0.014) mGy, 0.63 (0.011) mGy, 4.12 (0.050) mGy, 5.74 (0.082) mGy, 2.57 (0.024) mGy, 1.94 (0.017) mGy, 2.47 (0.073) mGy, and 0.09 (0.001) Gy cm2, 0.38 (0.012) Gy cm2, 0.32 (0.009) Gy cm2, 0.27 (0.052) Gy cm2, 0.17 (0.004) Gy cm2, 0.21 (0.006) Gy cm2, 1.18 (0.018) Gy cm2, 1.86 (0.023) Gy cm2, 1.41 (0.012) Gy cm2, 1.27 (0.010) Gy cm2, 1.28 (0.038) Gy cm2, as well as 0.01 (0.0001) mSv, 0.05 (0.0016) mSv, 0.02 (0.0006) mSv, 0.01 (0.0012) mSv, 0.03 (0.0008) mSv, 0.03 (0.0006) mSv, 0.26 (0.0038) mSv, 0.17 (0.0022) mSv, 0.20 (0.0016) mSv, 0.23 (0.0018) mSv, 0.23 (0.0068) mSv, respectively. The 75th percentiles along with the uncertainty U values for chest PA, chest LAT, cranium AP, cranium LAT, cervical spine AP, cervical spine LAT, lumbar spine AP, lumbar spine LAT, pelvis AP, abdomen AP, kidneys and urinary bladder (KUB) AP were 0.14 (0.006) mGy, 0.88 (0.031) mGy, 1.22 (0.049) mGy, 0.94 (0.098) mGy, 0.93 (0.027) mGy, 0.78 (0.013) mGy, 5.16 (0.073) mGy, 7.24 (0.134) mGy, 2.96 (0.047) mGy, 2.59 (0.036) mGy, 3.07 (0.116) mGy, as well as 0.10 (0.0006) Gy cm2, 0.51 (0.017) Gy cm2, 0.37 (0.020) Gy cm2, 0.33 (0.040) Gy cm2, 0.23 (0.007) Gy cm2, 0.26 (0.011) Gy cm2, 1.50 (0.036) Gy cm2, 2.26 (0.035) Gy cm2, 1.61 (0.023) Gy cm2, 1.67 (0.017) Gy cm2, 1.56 (0.069) Gy cm2, in terms of ESAK and KAP values, respectively. The results were significantly lower compared with the national reference levels, the most common DRL values reported at the European level and other previously reported dose values. Patient dose surveys could contribute towards optimising radiation protection for patients, therefore, highlighting the necessity to increase the awareness and knowledge of the radiation dose in conjunction with the required image quality.

Difficulties in Treating Postirradiation Kyphosis in Adults: A Series of Five Cases.

STUDY DESIGN: Clinical case series. OBJECTIVE: To assess objective outcomes of surgical correction of post-external beam radiation therapy (ERBT) kyphosis in a series of five adults. SUMMARY OF BACKGROUND DATA: EBRT is a well-established treatment for many cancers in children and adults. One complication associated with EBRT is postirradiation spine deformity. Scoliosis is the most common deformity, but kyphosis also occurs frequently. Differences in deformity patterns are likely related to the location and intensity of radiation. To our knowledge, no studies have addressed treatment of these deformities in adults, and the most recent case series (of children) was published in 2005. METHODS: We present a series of five adults who underwent surgery for postirradiation kyphosis, with a mean follow-up of 3.8 years (range, 2.5-6.2 years). RESULTS: Surgery improved the kyphotic deformity in all patients. Overall mean kyphotic deformity correction was 56° and was larger for cervical/cervicothoracic deformities (mean, 76°) than for lumbar deformities (mean, 42°) at midterm follow-up. Patients reported significant improvements in pain and self-image. Consistent with prior case series of children, we observed a high rate of complications (mean, 1.4 complications per patient) in adults. Three patients each underwent an unplanned surgical procedure because of a complication. CONCLUSION: The surgical treatment of postirradiation kyphotic spinal deformity is challenging, with common postoperative complications such as infection, instrumentation failure, and pseudarthrosis. However, with modern surgical techniques and spinal instrumentation, excellent deformity correction can be achieved and maintained. We recommend performing a two-stage procedure for cervicothoracic deformity, with anterior release followed by posterior fusion and instrumentation. In thoracolumbar deformities, correction can be achieved through single-stage posterior fusion. Rigid spinopelvic fixation with sacral-alar-iliac screws and second-stage anterior lumbar interbody fusion at L5-S1 is recommended to reduce nonunion risk. Cement augmentation of proximal and distal anchors can help prevent junctional failure. LEVEL OF EVIDENCE: Level IV.

Vertebral body growth after craniospinal irradiation.

PURPOSE: To estimate the effects of radiotherapy and clinical factors on vertebral growth in patients with medulloblastoma and supratentorial primitive neuroectodermal tumors treated with craniospinal irradiation (CSI) and chemotherapy. METHODS AND MATERIALS: The height of eight individual or grouped vertebral bodies (C3, C3-C4, T4, T4-T5, C6-T3, T4-T7, L3, L1-L5) was measured before and after CSI (23.4 or 36-39.6 Gy) in 61 patients. Of the 61 patients, 40 were boys and 21 were girls (median age, 7 years; range, 3-13 years), treated between October 1996 and October 2003. Sagittal T(1)-weighted magnetic resonance images were used for the craniocaudal measurements. The measurements numbered 275 (median, 5/patient; range, 3-7). The median follow-up after CSI was 44.1 months (range, 13.8-74.9 months). RESULTS: Significant growth was observed in all measured vertebrae. Excluding C3-C4, the growth rate of the grouped vertebrae was affected by age, gender, and CSI dose (risk classification). The risk classification alone affected the growth rates of C3 (p = 0.002) and L3 (p = 0.02). Before CSI, the length of all vertebral bodies was an increasing function of age (p <0.0001). The C3 length before CSI was affected by gender and risk classification: C3 was longer for female (p = 0.07) and high-risk (p = 0.07) patients. CONCLUSION: All vertebrae grew significantly after CSI, with the vertebrae of the boys and younger patients growing at a rate greater than that of their counterparts. The effect of age was similar across all vertebrae, and gender had the greatest effect on the growth of the lower cervical and upper thoracic vertebrae. The effect of the risk classification was greatest in the lumbar spine by a factor of < or = 10.

Cortical Thinning and Structural Bone Changes in Non-Human Primates after Single-Fraction Whole-Chest Irradiation.

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

Radiation Dose to the Thoracic Vertebral Bodies Is Associated With Acute Hematologic Toxicities in Patients Receiving Concurrent Chemoradiation for Lung Cancer: Results of a Single-Center Retrospective Analysis.

PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V5-V60) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points. RESULTS: We identified 201 patients, the majority having NSCLC (n=162, 81%) and stage III to IV disease (n=179, 89%). All patients received either cisplatin/etoposide (n=107, 53%) or carboplatin/paclitaxel (n=94, 47%). Median RT dose was 60 Gy (range, 60-70 Gy). The rate of HT3+ was 49% (n=99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004-1.080, P=.032), as were increasing TVB V5 to V20. These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n=1, m=1.79, and TD50=21.4 Gy. Optimal cut-points identified were V5=65%, V10=60%, V20=50%, and mean dose=23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. CONCLUSIONS: We found that mean TVB dose and low-dose parameters (V5-V20) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n=1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.

Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer.

PURPOSE: Radiation therapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumor control in esophageal cancer; however, any increase in acute hematologic toxicity (HT) could limit the predicted improvement in patient outcomes. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy. Therefore, we investigated the potential of bone marrow sparing with protons for esophageal tumors. METHODS AND MATERIALS: Twenty-one patients with mid-esophageal cancer who had undergone conformal radiation therapy (3D50) were selected. Two surrogates for bone marrow were created by outlining the thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse. The percentage of overlap of the TV with the planning treatment volume was recorded for each patient. Additional plans were created retrospectively, including a volumetric modulated arc therapy (VMAT) plan with the same dose as for 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high-risk subregion within the planning treatment volume; a reoptimized TV-sparing VMAT plan; and a proton therapy plan with the same SIB dose prescription. The bone and TV dose metrics were recorded and compared across all plans and variations with respect to PTV and percentage of overlap for each patient. RESULTS: The 3D50 plans showed the highest bone mean dose and TV percentage of volume receiving ≥30 Gy (V30Gy) for each patient. The VMAT plans irradiated a larger bone V10Gy than did the 3D50 plans. The reoptimized VMAT62.5 VT plans showed improved sparing of the TV volume, but only the proton plans showed significant sparing for bone V10Gy and bone mean dose, especially for patients with a larger PTV. CONCLUSIONS: The results of the present study have shown that proton therapy can reduced bone marrow toxicity.