Radiation-induced Rib Fracture Research Articles

Symptomatic radiation-induced rib fractures after stereotactic body radiotherapy for early-stage non-small cell lung cancer

Background and purposeThe present study investigated the relationships between the risk of radiation-induced rib fractures (RIRF) and clinical and dosimetric factors in stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). We also examined dosimetric parameters associated with symptomatic or asymptomatic RIRF and the dosimetric threshold for symptomatic RIRF. Materials and methodsWe reviewed 244 cases of early-stage NSCLC treated with SBRT. Gray’s test and the Fine-Gray model were performed to examine the relationships between clinical and dosimetric factors and grade ≥ 2 (i.e., symptomatic) RIRF. The effects of each dose parameter on grade ≥ 1 and ≥ 2 RIRF were assessed with the Fine-Gray model. The t-test was used to compare each dose parameter between the grade 1 and grade ≥ 2 groups. Optimal thresholds were tested using receiver operating characteristic (ROC) curves. ResultsWith a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥ 1 and grade ≥ 2 RIRF were 26.4 % and 8.0 %, respectively. Regarding clinical factors, only age was associated with the development of grade ≥ 2 RIRF (p = 0.024). Among dosimetric parameters, only V40Gy significantly differed between the grade 1 and grade ≥ 2 groups (p = 0.015). The ROC curve analysis of grade ≥ 2 RIRF showed that the optimal diagnostic thresholds for D3cc, D4cc, D5cc, and V40Gy were 45.86 Gy (area under the curve [AUC], 0.706), 39.02 Gy (AUC, 0.705), 41.62 Gy (AUC, 0.702), and 3.83 cc (AUC, 0.730), respectively. These results showed that V40Gy ≤ 3.83 cc was the best indicator of grade ≥ 2 RIRF. The 4-year incidence of grade ≥ 2 RIRF in the V40Gy ≤ 3.83 cc vs. > 3.83 cc groups was 1.8 % vs. 14.2 % (p = 0.001). ConclusionThe present results recommend V40Gy ≤ 3.83 cc as the threshold for grade ≥ 2 RIRF in SBRT.

Predictive Model for the Radiotherapy Induced Rib Fracture (RIRF) after Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> To identify clinical and dosimetric factors associated with the radiation-induced rib fracture (RIRF) after stereotactic body radiotherapy (SBRT), and to provide more appropriate ribs dose constraints. <h3>Materials/Methods</h3> Patients treated with SBRT for primary or metastatic lung tumors within 1 cm from Ribs, and had no previous overlapping radiation exposure were eligible to this study. Clinical factors, rib bone mineral density (BMD) and dosimetric parameters were evaluated for their associations with RIRFs. All cases were reviewed by experienced radiologists to detect and grade RIRF using the radiological as well as clinical toxicity data, as per CTCAE v5.0. Variable filtering was done through the least absolute shrinkage and selection operator (Lasso). A dose-event curve and predictive model were created. Calibration Curves were used to evaluate model prediction accuracy. <h3>Results</h3> A total of 160 patients with 165 lesions were eligible. After a median follow-up of 26.2 months (range: 10.5 – 62.6), 46 RIRFs were detected (27.9%) , including 20(42.6%) Grade 1 RIRFs, 25(53.2%) Grade 2 RIRFs and only 1 Grade 3 RIRF. The median interval from SBRT to RIRF detection was 16 months (range: 6.33-45.30). Of the 68 fractured ribs, 52 (76.5%) developed in ribs 2-5. 3 optimal dosimetric parameters and 1 optimal rib BMD parameter were filtered from 82 dosimetric parameters and 12 rib BMD parameters. As these three dosimetric parameters were cross-correlated, we selected Rib-BED₃D1.4cc as the representative dosimetric predictor, who's cut-off value (α/β=3, LQ-model, Rib-BED₃D1.4cc=212.16Gy) was extraordinarily higher than the AAPM Task Group 101 dose constrains for ribs (Rib-BED₃D1cc<120.96Gy for 3 fractions, 116.67Gy for 5 fractions). Multivariate analysis showed that the rib location of the maximum dose point (Dmax Rib, odds ratio:21.491, p=0.018), mean density of the rib cortex (Cortex mean, odds ratio: 0.995, p = 0.018) and Rib-BED₃D1.4cc (odds ratio: 1.013, p = 0.004) were all significantly associated with the RIRF. The final predictive logistic model for RIRFs included Dmax Rib, Cortex mean and Rib-BED₃D1.4cc had significantly better predictive ability than any of the dosimetric predictor alone (AUC 0.791 vs 0.701, p = 0.0336). A nomogram was constructed based on the logistic model. <h3>Conclusion</h3> This study developed and validated a comprehensive model integrating rib BMD parameters with dosimetric factors to predict RIRFs. A predictive nomogram of AUC of 0.79 may provide an opportunity to guide clinicians. For the dosimetric predictor alone, we suggest that Rib-BED₃D1.4cc less than 212.16Gy would be more appropriate.

The Effectiveness of Proton Beam Therapy for Liver Metastatic Lesions in Colorectal Cancer Patients

<h3>Purpose/Objective(s)</h3> The purpose of this study was to evaluate the efficacy and safety of proton beam therapy (PBT) for liver metastatic (LM) lesion in colorectal cancer (CRC) patients. <h3>Materials/Methods</h3> Consecutive CRC patients who underwent PBT for ≤3 LM lesions from 2009 to 2018 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. The effectiveness was assessed based on the local control (LC), overall survival (OS) and progression-free survival (PFS) rates. The LC, OS and PFS rates were calculated using the Kaplan–Meier method and log-rank test. Factors that may be related to LC, such as tumor size, fraction size, BED₁₀ and the distance from the lesion to the most recently involved intestinal tract were investigated. The cut-off values were estimated using the ROC curve and AUC. P-values below 0.05 were consider significant. Adverse events were described according to CTCAE ver 5.0. <h3>Results</h3> This study included 23 men and 18 women whose median age was 66 years (24 - 87 years). Sixty-three lesions were enrolled. The most frequent dosage was 72.6 Gy (RBE) /22fr. The median lesion size, fraction size, BED₁₀, the distance between LM lesion and adjacent were 30 mm (9-103 mm), 3.3 Gy(RBE)/fr (2-8 Gy(RBE)/fr),105.6 Gy(RBE) (72-154.7 Gy(RBE)), 42.4mm (0-147mm), respectively. The median follow-up period was 27.6 months (5.2-84.7 months). As of November 2020, 20 patients died (including one of intercurrent disease death). The 3-year LC, OS and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Twenty-three lesions were local recurrence which of five lesions were surgically removed and one lesion was re-irradiated with PBT. Both re-treatments after PBT were performed safely and without complications. Distant metastasis occurred in 24 patients. The most common site of distant metastasis was the lung with 11 patients. Any statistically significant LC related factors were not found. However, the P-value for tumor size was the smallest, P=0.0665. The 2-year LC rates in the group with less than 14.1 mm and the larger group were 100% and 50%, respectively. and 50%, respectively. No grade ≥3 adverse events were observed. No patients experienced liver failure in the acute or late phase. The only acute adverse event was one cases of G2 dermatitis radiation. The only late adverse effect was three cases of G1 radiation-induced rib fracture. <h3>Conclusion</h3> PBT might be a treatment option for patients with liver metastasis of CRC. Tumor size tended to be associated with local control rates.

OA14.04 Chest Wall Toxicity after Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Chest wall toxicity (CWT), comprising chest wall (CW) pain and radiation-induced rib fracture, is a common adverse effect of lung stereotactic ablative radiotherapy (SABR) for treatments near the CW. However, there is currently no clear consensus on dosimetric constraints or fractionation schemes (single versus multiple) to mitigate this toxicity. The goal of this analysis is to identify predictive dosimetric parameters for CWT and to compare outcomes for patients undergoing single- vs. multi-fraction SABR.

Effects of Tumor-Rib Distance and Dose-Dependent Rib Volume on Radiation-Induced Rib Fractures in Patients with Breast Cancer.

This study aimed to investigate the effects of tumor-rib distance and dose-dependent rib volume on radiation-induced rib fractures (RIRFs) in patients with breast cancer. We retrospectively included 510 women with breast cancer who underwent surgical resection with adjuvant radiotherapy. The tumor-rib distance was measured using preoperative computed tomography (CT) images. Postoperative chest wall thickness and dose-dependent rib volumes, which are absolute rib volumes receiving >20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 45 Gy (V45), and 50 Gy (V50), were measured from the stimulation CT images for radiation treatment planning. We assessed the relationship of RIRF with tumor-rib distance, postoperative chest wall thickness, and dose-dependent rib volumes. Patients with high values of tumor-rib distance and postoperative chest wall thickness had significantly lower risks of RIRF than those with low values. Patients with high values of V20, V30, V40, V45, and V50 had significantly higher risks of RIRF than those with low values. In a multivariate analysis, tumor-rib distance and all five dose-dependent rib volumes, as well as osteoporosis and radiation field, were independent risk factors for RIRF. Tumor-rib distance and dose-dependent rib volume were independent risk factors for RIRF in patients with breast cancer.

Delivered dose–effect analysis of radiation induced rib fractures after thoracic SBRT

Background and purposeAnatomical changes during the stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC) may cause the delivered dose to deviate from the planned dose. We investigate if normal tissue complication probability (NTCP) models based on the delivered dose predict radiation-induced rib fractures better than models based on the planned dose. Material and methods437 NSCLC patients treated to a median dose of 3x18 Gy were included. Delivered dose was estimated by accumulating EQD2-corrected fraction doses after being deformed with daily CBCT-to-planning CT deformable image registration.Dosimetric parameters Dx (dose to a relative volume x) were extracted for each rib included in the CBCTs field-of-view. An NTCP model was constructed for both planned and delivered dose, optimizing the parameters TD50 (dose with 50% toxicity risk), m (steepness of the curve) and x, using maximum likelihood estimation. Best NTCP model was determined using Akaike weights (Aw). Differences between the models were tested for significance using the Vuong’s test. ResultsMedian time to fracture of 110 fractured ribs was 22.5 months. The maximum rib dose, D0, best predicted fractures for both planned and delivered dose. The average delivered D0 was significantly lower than planned (p < 0.001). NTCP model based on the delivered D0 was the best, with Aw = 0.95. The models were not significantly different. ConclusionDelivered maximum dose to the ribs was significantly lower than planned. The NTCP model based on delivered dose improved predictions of radiation-induced rib fractures but did not reach statistical significance.

Radiomic Features Predict Rib Fracture after Stereotactic Body Radiotherapy for Early Stage Non-Small Cell Lung Cancer

Dose to the chest wall is a well-established predictor of rib fracture after stereotactic body radiation therapy (SBRT), but even with a high dose to the chest wall most patients will not develop a fracture. Discovering other predictors that are independent from dose will improve our ability to predict which patients will develop a rib fracture. Radiomic analysis of the chest wall can provide an opportunity to find such features on imaging. A retrospective analysis was conducted of 73 patients with early stage NSCLC who were treated with SBRT. Quantitative radiomic feature extraction using PyRadiomics was performed on the 4D treatment planning scans of all patients. A total of 236 radiomic features were extracted, all of which were based on a Boolean overlap of the 20 Gy isodose volume and the chest wall. A 10-fold cross validation based Elastic Net Cox regression was completed for variable selection and used to identify the lambda (regularization parameter) value that produced the lowest cross-validated error. Variables that remained in the final model were then evaluated independently with univariate Cox regression hazard ratios and in a multivariate model built with and without the radiomic features and compared based on concordance indexes that were averaged across a Monte Carlo cross-validation scheme with 10 resamples. Correlation between predictors was evaluated using Pearson’s correlation coefficient. Twenty-nine patients with radiation induced rib fractures were identified retrospectively and compared to 44 patients with no rib fracture. The Elastic Net Cox regression model with the lowest cross-validated error included 6 predictors: three clinical and three radiomic. The clinical variables included volume of overlap between the PTV and chest wall (HR 2.49, p < 0.01), volume of chest wall receiving 50 Gy (HR 2.23, p < 0.01) and volume of rib receiving 50 Gy (HR 2.14, p < 0.01). Radiomic variables included shape elongation (HR 0.64, p = 0.03), Gray Level Size Zone Matrix (GLSZM) Large Area Low Gray Level Emphasis (LALGLE; HR 2.24, p < 0.01) and Neighboring Gray Tone Difference Matrix (NGTDM) busyness (HR 2.36, p < 0.01). A multivariate model that included only the clinical variables had a concordance index of 0.69 (95% CI 0.61-0.77) while inclusion of the radiomic variables increased the concordance index to 0.79 (95% CI 0.76 to 0.82). Of the 3 identified radiomic features, shape elongation was the least correlated with the clinical variables. The Pearson correlation coefficient comparing shape elongation to chest wall V50 was 0.03 (95% CI -0.20 to 0.25, p = 0.824). Radiomic feature extraction from the chest wall can provide insight into a patient’s risk of a rib fracture after SBRT. Of the radiomic features found to persist in the final multivariate model, shape elongation was the only variable not correlated with chest wall dose. This provides evidence for a predictor of rib fracture after SBRT that is independent of chest wall dose.

Calculating the Individualized Fraction Regime in Stereotactic Body Radiotherapy for Non-Small Cell Lung Cancer Based on Uncomplicated Tumor Control Probability Function

To calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P+) function. 33 patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose was multiplied from 1% to 200% at a resolution of 1%. For each dose fraction, P+ values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P+ values corresponded to the optimal therapeutic gain. IFR in 3 fractions was also calculated with the same method by converted the dose using the linear quadratic (LQ) model. 33 patients attained an IFR using the introduced methods. All the patients achieved TCP value higher than 92.0%. The IFR ranged from 3×10.8 Gy to 3×12.5 Gy for 3 fraction regimes and from 4×9.2 Gy to 4×10.7 Gy for 4 fraction regimes, respectively. Four patients with typical tumor characteristics demonstrated the IFR was patient-specific and could maximize the therapeutic gain. Patients with large tumor were associated with lower TCP, UTCP and smaller fractional dose than patients with small tumor. Patients with tumor adjacent to the organ at risk (OAR) or at high risk of RIP showed lower UTCP and smaller fractional dose compared with patients with tumor away from the OAR. The proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation is required in clinical samples.

Calculating the individualized fraction regime in stereotactic body radiotherapy for non-small cell lung cancer based on uncomplicated tumor control probability function

BackgroundTo calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P+) function.MethodsThirty-three patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose bin was multiplied by a certain percentage of the dose in that bin which ranged from 1 to 200% in steps of 1%. For each dose fraction, P+ values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P+ values corresponded to the optimal therapeutic gain. The IFR in 3 fractions was also calculated with the same method by converting the dose using the linear quadratic (LQ) model.ResultsThirty-three patients attained an IFR using the introduced methods. All the patients achieved a TCP value higher than 92.0%. The IFR ranged from 3 × 10.8 Gy to 3 × 12.5 Gy for 3 fraction regimes and from 4 × 9.2 Gy to 4 × 10.7 Gy for 4 fraction regimes. Four patients with typical tumor characteristics demonstrated that the IFR was patient-specific and could maximize the therapeutic gain. Patients with a large tumor had a lower TCP and UTCP and a smaller fractional dose than patients with a small tumor. Patients with a tumor adjacent to the organ at risk (OAR) or at a high risk of RIP had a lower UTCP and a smaller fractional dose compared with patients with a tumor located distant from the OAR.ConclusionsThe proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation in clinical samples is required.

Efficacy and safety of a simplified SBRT regimen for central and peripheral lung tumours

Evaluate the safety, toxicity and efficacy of an institutional-simplified SBRT protocol with two short SBRT regimens (three or five fractions) for the treatment of lung cancer and oligometastases, according to the volume and localization of tumours. Patients with stage I (T1 or T2) non-small cell lung cancer or lung oligometastases were treated from August 2011 to October 2015. Patients were required to be considered medically inoperable and were discussed in a multidisciplinary team. 100 patients were analysed, 59 had a peripheral location (P), and 41 a central location (C).All patients finished their SBRT course without interruptions related to acute toxicity. The most frequent acute toxicity was grade 1 asthenia, only one patient developed grade 3 toxicity (pneumonitis) and there were no grade 4 or 5 acute toxicities. Three asymptomatic radiation-induced rib fractures were identified, the 1 and 2-year rib fracture-free survival were 97% and 94%, respectively. Two-year progression-free survival and 2-year overall survival of all patients were 52% and 70%, respectively, with a median PFS and OS of 26 and 43months. Survival free of local progression (SFLP) at 2years was 89%. A higher PFS in primary lung cancer compared with metastatic tumours was observed, with a median of 35months with 19months (p = 0.01). However, no statistical difference was observed in terms of OS between both diseases. SBRT in lung cancer with three sessions for peripheral tumours and five sessions for central tumours may be safely delivered, with low morbidity.

Characterization of Chest Wall Toxicity During Long-term Follow Up After Thoracic Stereotactic Body Radiation Therapy

PurposeChest wall (CW) pain and rib fractures are frequently diagnosed after stereotactic body radiation therapy (SBRT) for malignant lung tumors. We hypothesize that multiple risk factors, including bone mineral density (BMD), are associated with CW toxicity, and that CW pain and rib fractures often evolve into chronic clinical problems. Methods and materialsA total of 118 lung tumors treated with SBRT in 100 patients with a minimum follow-up period of 2 years were retrospectively analyzed. The incidence, clinical course, and related demographic, clinical, and dosimetric factors of CW pain and rib fractures were analyzed. In addition, BMD was assessed, and the radiographic appearance of radiation-induced rib fractures and their healing process were characterized. ResultsThe median follow-up was 49 months (range, 24-106 months). CW pain developed in 33 of 118 treatments (28%) after, on average, 12.5 months (range, 0-50 months), and was more common in women (P = .04). The mean duration of CW pain was 25 months (range, 2-63 months), and 36% of patients never had resolution of CW pain. A total of 34 of 118 treatments (29%) resulted in rib fractures at a mean time of 22 months (range, 3-46 months); rib fractures were more common in women, African Americans, upper/middle lobe tumors, and patients with lower BMD (P < .05). The mean duration of rib fractures was 25 months (range, 5-41 months), and only 16 rib fractures (47%) healed. Shorter CW planning target volume distance resulted in a higher risk for both rib fractures and CW pain (P = .01). Sixty-seven percent of fractures developed surrounding soft tissue fibrosis, and 62% (21 of 34 fractures) heterotopic ossification. Diabetes, body mass index, and steroid use were not associated with CW pain or rib fracture. ConclusionsSeveral factors were associated with a higher risk of SBRT-related CW toxicity. Optimal CW sparing (eg, volumetric modulated arc therapy, lower dose per fraction) should be considered in this patient group without compromising tumor control. SBRT-induced rib fractures commonly heal abnormally and result in potential chronic CW pain.

Long Term Radiographic and Clinical Course in Chest Wall Toxicity following Thoracic Stereotactic Body Radiation Therapy

Stereotactic Body Radiotherapy (SBRT) for malignant lung lesions is known to potentially cause chest wall (CW) toxicity, however the long term course of these side effects is not well described. We hypothesize that radiation-induced rib fractures frequently do not radiographically heal fully and are closely associated with prolonged CW pain in areas of high doses. One-hundred ten lung tumors treated with SBRT in 101 patients (61 female, 40 male) were retrospectively analyzed. Only patients with a minimum follow up of 2 years were included. The most common treatment regimen was 48GY/4fx. The incidence, clinical course, and related dosimetric and clinical factors of CW toxicity are analyzed. In addition, the radiographic appearance of radiation induced rib fractures and their healing process are characterized. Statistical results were obtained using Mann-Whitney U-test and Chi-Square test. Mean follow up was 48 months (range 24-100), mean age at treatment of 68 years (range 47-91). Overall, 29% (32/110) of treatments resulted in rib fractures (cumulative 50 fractured ribs) after on average 23 months (range 1-46). Of the 32 treatments resulting in rib fracture, 66% (20/32) developed CW pain and 56% (18/32) fractured more than one rib, including 10 treatments with 3 or more resulting rib fractures. 31% (34/110) treatments resulted in CW pain occurring at a mean time of 12 months (range 1-50) with mean duration of 22 months (range 2-63); 38% (13/34) had ongoing pain at time of last follow up . Interestingly only 62% (20/34) treatments with CW pain had associated rib fractures. Clinically, women and African Americans were more likely to develop rib fractures (p<0.01 and p=0.01 respectively); while older patients and women were more likely to develop CW pain (p=0.02 and p=0.006 respectively). CW V20Gy, V30Gy, V40Gy, Dmax and D30cc were higher in patients with rib fractures (p<0.05 in all). The PTV was abutting CW in all but 1 patient who developed rib fractures while the mean distance to CW in patients without rib fracture was 1cm (range 0-4.4); p=0.016. Radiographically, only 16% (8/50) ribs were fully healed at last imaging, 76% (38/50) displayed soft tissue fibrosis and 20% (10/50) had commuted fractures. Bone Density was measured but no differences were found between patients with or without rib fracture or CW pain (p>0.05). Thoracic SBRT is associated with a non-negligible risk of rib fracture and CW pain which can occur late after RT. Radiation induced rib fractures are unlikely to fully heal radiographically and can subsequently result in CW pain with long duration. High doses to the CW are most likely to put patients at risk and should be minimized as much as possible, particularly in females.

Radiation-induced rib fractures after stereotactic body radiation therapy: Predict to prevent?

Radiation-induced rib fractures after stereotactic body radiation therapy: Predict to prevent?

Clinical outcome of stereotactic body radiotherapy for primary and oligometastatic lung tumors: a single institutional study with almost uniform dose with different five treatment schedules.

BackgroundTo evaluate clinical outcomes of stereotactic body radiotherapy (SBRT) for localized primary and oligometastatic lung tumors by assessing efficacy and safety of 5 regimens of varying fraction size and number.MethodsOne-hundred patients with primary lung cancer (n = 69) or oligometastatic lung tumors (n = 31), who underwent SBRT between May 2003 and August 2010, were included. The median age was 75 years (range, 45–88). Of them, 98 were judged to have medically inoperable disease, predominantly due to chronic illness or advanced age. SBRT was performed using 3 coplanar and 3 non-coplanar fixed beams with a standard linear accelerator. Fraction sizes were escalated by 1 Gy, and number of fractions given was decreased by 1 for every 20 included patients. Total target doses were between 50 and 56 Gy, administered as 5–9 fractions. The prescribed dose was defined at the isocenter, and median overall treatment duration was 10 days (range, 5–22).ResultsThe median follow-up was 51.1 months for survivors. The 3-year local recurrence rates for primary lung cancer and oligometastasis was 6 % and 3 %, respectively. The 3-year local recurrence rates for tumor sizes ≤3 cm and >3 cm were 3 % and 14 %, respectively (p = 0.124). Additionally, other factors (fraction size, total target dose, and BED10) were not significant predictors of local control. Radiation pneumonia (≥ grade 2) was observed in 2 patients. Radiation-induced rib fractures were observed in 22 patients. Other late adverse events of greater than grade 2 were not observed.ConclusionWithin this dataset, we did not observe a dose response in BED10 values between 86.4 and 102.6 Gy. SBRT with doses between 50 and 56 Gy, administered over 5–9 fractions achieved acceptable tumor control without severe complications.

Incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture after carbon ion radiotherapy for lung cancer

Background: The purpose of this study was to assess the incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture (RIRF) after carbon ion radiotherapy for lung cancer.Material and methods: Fifty-seven ribs of 18 patients with peripheral stage I non-small cell lung cancer treated with carbon ion radiotherapy were analyzed on rib fracture. The patients were treated at a total dose of 52.8 Gy [relative biologic effectiveness (RBE)] or 60.0 Gy (RBE) in 4 fractions and were followed at least six months. Patient characteristics and dosimetric parameters were analyzed for associations with RIRF.Results: Eighteen patients and 57 ribs were included in this study. The median length of follow-up was 36.5 months. RIRF was observed in seven (39%) of the 18 patients, and in 11 (19%) of 57 ribs. Only one patient developed symptomatic fracture. The distance from the ribs to the tumor site was significantly shorter in fractured ribs than in non-fractured ribs (1.4 ± 0.3 cm vs. 2.5 ± 0.3 cm). Receiver operating characteristic curve analysis showed that as a cut-off value for discriminating RIRF had the largest area under the curve (AUC =0.78). Comparison of the two-year cumulative incidence of RIRF among two groups as determined by cut-off values, yielded the following result: 53% vs. 4% [, ≥ 38.2 Gy (RBE) or less]. Results from the two groups were significantly different (p < 0.05).Conclusion: The crude incidence of RIRF after carbon ion radiotherapy was 39% but incidence of symptomatic fracture was low. The as cut-off values may be helpful for discriminating the risk of RIRF.

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

BackgroundRadiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor.MethodsDuring 2003–2008, 41 patients with 42 lung tumors were treated with SBRT to 54–56 Gy in 9–7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study.ResultsMedian follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16–48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10–55, age, sex, and planning target volume were not significantly different.ConclusionsThe doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

The Incidence of Radiation Induced Rib Fractures (RIRF) Following Stereotactic Body Radiation Therapy (SBRT) With Fiducial Tracking for Peripheral Stage I Non-small Cell Lung Cancer (NSCLC)

The Incidence of Radiation Induced Rib Fractures (RIRF) Following Stereotactic Body Radiation Therapy (SBRT) With Fiducial Tracking for Peripheral Stage I Non-small Cell Lung Cancer (NSCLC)

Radiation-induced Rib Fracture After Hypofractionated Stereotactic Body Radiation Therapy for Patients With Peripheral Lung Tumor: Impact of the Maximum Dose and the Fraction Size

Radiation-induced Rib Fracture After Hypofractionated Stereotactic Body Radiation Therapy for Patients With Peripheral Lung Tumor: Impact of the Maximum Dose and the Fraction Size

Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma

Background. Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). Material and methods. The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients’ characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. Results. Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p ≥ 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy3 (RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy3] and the AUCs of V30 to V120 (EQD2; 18–72 Gy3) and Dmax to D10cm3 were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. Conclusion. DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and Dmax to D10cm3 were also significant and clinically useful for estimating the risk of rib fracture after hypofractionated PBT.

Radiation-Induced Rib Fractures After Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors and Dose–Volume Relationship

The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose-volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT). One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib-tumor distance, and use of steroid administration, were analyzed. Dose-volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves. One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose,≥42.4 Gy or less), 51.6% vs. 2.0% (V40, ≥0.29 cm(3) or less), 45.8% vs. 2.2% (V30,≥1.35 cm(3) or less), 42.0% vs. 8.5% (V20, ≥3.62 cm(3) or less), or 25.9% vs. 10.5% (V10, ≥5.03 cm(3) or less). The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF.