Dynamics in the expression of programmed death ligand 1 and cluster of differentiation 163 in the tumor microenvironment of uterine cervical cancer: a single-center retrospective study.

BACKGROUND: Radiotherapy (RT) destroys cancer cells and activates the immune system while suppressing the immunity of tumor-associated tissues, including the tumor microenvironment (TME). However, to date, no anti-tumor therapeutic strategy that uses these immune mechanisms has been established. This study investigated changes in the immunity of the TME during standard radical RT for cervical cancer combined with external beam RT and brachytherapy and determined whether these changes affect prognosis. METHODS: Twenty-six patients who had completed radical RT for cervical cancer were categorized into the following two groups according to whether the cancer recurred and/or metastasized within 2 years after the start of treatment: treatment failure (n = 14) and treatment success (n = 12). We assessed the expression of programmed death 1, programmed death ligand 1 (PD-L1), cluster of differentiation (CD) 8, CD68, CD163, Forkhead box protein P3, and hypoxia-inducible factor-1α in the TME of cervical tissues collected periodically during treatment and evaluated the difference in expression rates of each marker between the success and failure groups and assessed its effect on prognosis. RESULTS: The expression levels of PD-L1 and CD163 in the TME in the treatment success group were lower than those in the treatment failure group at the midpoint during brachytherapy (p < 0.01 and p = 0.08, respectively), and the 2-year progression-free-survival (PFS) rate depended on the expression levels of PD-L1 and CD163 (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: The expression rates of CD163 and PD-L1 in the TME during brachytherapy were related to treatment response and the 2-year PFS. This study may increase our understanding of tumor-associated immunity in the TME and aid in the development of therapies targeting PD-L1 or M2 macrophages in the TME in conjunction with RT, especially brachytherapy, for cervical cancer patients.

Phase II study of vinorelbine plus carboplatin with concurrent radiotherapy in elderly patients with non-small cell lung cancer.

OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. PURPOSE: To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. METHODS: This multicenter, phase II study included patients with physiologically or medically unresectable stage I-III NSCLC, who were ≥70 years old. The patients received carboplatin (AUC 2) and vinorelbine (15 mg/m2) both on day 1, 8, 22 and 29 concurrently with radiotherapy (2.0 Gy/day, 30 fractions, total 60 Gy). The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival, overall survival and the incidence of adverse events. RESULTS: 50 patients were accrued (42 men and 8 women). The median age was 77 years (range, 70-89 years) and the clinical stage was I/II/III in 3/7/40, respectively. Forty-seven patients completed the planned treatment. The response was complete remission in 4, partial response in 31, stable disease in 12 and progressive disease in 3, giving an objective response rate of 70% (95% confidence interval: 55.4-82.1). Frequent high Grade 3 or higher adverse events were hematologic, but no treatment deaths were noted. The median and 2-year progression-free survival were 8.4 months and 21.1% (95% confidence interval: 9.5-32.7%), respectively, and the median and 2-year overall survival were 15.4 months and 41.1% (95% confidence interval: 27.0-55.2), respectively. CONCLUSION: Concurrent chemoradiotherapy with carboplatin and vinorelbine showed an acceptable objective response rate and safety in elderly patients.

Possibility of chest wall dose reduction using volumetric-modulated arc therapy (VMAT) in radiation-induced rib fracture cases: comparison with stereotactic body radiation therapy (SBRT).

The present study compares dosimetric parameters between volumetric-modulated arc therapy (VMAT) and 3D conformal radiation therapy (3D-CRT) in lung tumors adjacent to the chest wall treated with stereotactic body radiation therapy (SBRT). The study focused on the radiation dose to the chest wall of 16 patients who had developed radiation-induced rib fractures (RIRF) after SBRT using 3D-CRT. The targets in all patients were partially overlapping with the fractured ribs, and the median overlapping rib-PTV distance was 0.4 cm. Stereotactic body radiation therapy was re-planned for all patients. The prescribed dose was 48 Gy in four fractions to cover at least 95% of the planning target volume (PTV). Evaluated dosimetric factors included D98% and the conformation number (CN) of the PTV, the D2cm3, V40 and V30 of the fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung. A comparison of 3D-CRT with the VMAT plan for PTV revealed that CN was significantly improved in the VMAT plan, whereas D98% did not significantly differ between the two plans. Regarding organs at risk (OARs), the D2cm3, V40 and V30 of fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung, were significantly decreased in the VMAT plan. We concluded that the dose to OARs such as ribs and chest wall could be reduced with improved target conformity using VMAT instead of 3D-CRT for SBRT to treat peripheral lung tumors.

Cardiac and respiratory effects of deep regional hyperthermia using an 8 MHz radiofrequency-capacitive device on patients with cancer.

PURPOSE: Hyperthermia (HT), an adjuvant therapy for variable cancers, may cause physiological changes in the patients, which may lead to cardiovascular problems. Among various HT treatments, the physiological effects of deep regional HT are still unclear. We examined the physiological alterations throughout deep regional HT to improve the HT safety. MATERIALS AND METHODS: Thirty-one patients (age: 61 ± 12 years) with cancer received HT in the thoracic or upper abdominal regions using an 8-MHz radiofrequency-capacitive-device for 50 min. Rectal temperature (Trec), systolic and diastolic blood pressures (SBP and DBP), pulse rate (PR), respiratory rate (RR), percutaneous oxygen saturation (SpO2) and sweating volume were evaluated throughout HT. RESULTS: At 50 min after starting HT, Trec, PR and RR were significantly increased compared with the baseline values (Trec: 38.2 ± 1.4 vs. 36.3 ± 0.8 °C, p < 0.001, PR: 104 ± 15 vs. 85 ± 16 bpm, p < 0.05, RR: 23 ± 3 vs. 21 ± 3/min, p < 0.05). Although the average SBP and DBP were both stable during HT in a recumbent position, these values dropped significantly in a standing position (SBP: 113 ± 16 vs. 127 ± 18 mmHg, p < 0.001, DBP: 70 ± 12 vs. 75 ± 13 mmHg, p < 0.01). The total amount of sweating was 356 ± 173 g/m2 on average. CONCLUSIONS: Deep regional HT increased the deep body temperature and resulted in an increase of sweating with peripheral vasodilatation. Consequently, a significant reduction in BP would be induced on standing after HT. Careful attention is needed for patients receiving HT, especially when standing after HT.

Investigation of whether in-room CT-based adaptive intracavitary brachytherapy for uterine cervical cancer is robust against interfractional location variations of organs and/or applicators.

This study investigates whether in-room computed tomography (CT)-based adaptive treatment planning (ATP) is robust against interfractional location variations, namely, interfractional organ motions and/or applicator displacements, in 3D intracavitary brachytherapy (ICBT) for uterine cervical cancer. In ATP, the radiation treatment plans, which have been designed based on planning CT images (and/or MR images) acquired just before the treatments, are adaptively applied for each fraction, taking into account the interfractional location variations. 2D and 3D plans with ATP for 14 patients were simulated for 56 fractions at a prescribed dose of 600 cGy per fraction. The standard deviations (SDs) of location displacements (interfractional location variations) of the target and organs at risk (OARs) with 3D ATP were significantly smaller than those with 2D ATP (P < 0.05). The homogeneity index (HI), conformity index (CI) and tumor control probability (TCP) in 3D ATP were significantly higher for high-risk clinical target volumes than those in 2D ATP. The SDs of the HI, CI, TCP, bladder and rectum D2cc, and the bladder and rectum normal tissue complication probability (NTCP) in 3D ATP were significantly smaller than those in 2D ATP. The results of this study suggest that the interfractional location variations give smaller impacts on the planning evaluation indices in 3D ATP than in 2D ATP. Therefore, the 3D plans with ATP are expected to be robust against interfractional location variations in each treatment fraction.

[Effect of prostate matching on dose distribution by on board imager kV-CBCT image].

PURPOSE: The purpose of this study was to evaluate the effect of prostate matching on dose distribution using kilovolt cone beam computed tomography (kV-CBCT) with image guided radiation therapy for prostate cancer. MATERIALS AND METHOD: Sixteen prostate cancer patients were treated with intensity modulated radiation therapy to 76 Gy at 2 Gy per fraction in 38 fractions. Daily target localization was performed using "bone matching" and "prostate matching" based on planning CT and kV-CBCT. Prostate dose coverage was assessed by the proportion of the CTV fully encompassed by 95%, 98% isodose lines, and mean dose lines. As for rectal and bladder, dose coverage was assessed by volumes which received 40 Gy, 60 Gy, 70 Gy, 75 Gy and mean dose at treatment. And we calculated the tumor control probability (TCP) and normal tissue complication probability (NTCP), accordingly. They were compared to the bone and prostate matching image. RESULT: Our study found an improvement in dose usage in CTV and bladder which enabled us to compare the bone matching image and the prostate matching image. However, it did not improve dose usage in the rectal. Then we chose patients who were a large shift from bone matching image to prostate matching image. As a result, rectal dose and NTCP were reduced. DISCUSSION: Prostate matching is useful and safe when compared to bone matching because of improving CTV dose usage and reducing dose rectal and bladder.

A computerized framework for monitoring four-dimensional dose distributions during stereotactic body radiation therapy using a portal dose image-based 2D/3D registration approach.

A computerized framework for monitoring four-dimensional (4D) dose distributions during stereotactic body radiation therapy based on a portal dose image (PDI)-based 2D/3D registration approach has been proposed in this study. Using the PDI-based registration approach, simulated 4D "treatment" CT images were derived from the deformation of 3D planning CT images so that a 2D planning PDI could be similar to a 2D dynamic clinical PDI at a breathing phase. The planning PDI was calculated by applying a dose calculation algorithm (a pencil beam convolution algorithm) to the geometry of the planning CT image and a virtual water equivalent phantom. The dynamic clinical PDIs were estimated from electronic portal imaging device (EPID) dynamic images including breathing phase data obtained during a treatment. The parameters of the affine transformation matrix were optimized based on an objective function and a gamma pass rate using a Levenberg-Marquardt (LM) algorithm. The proposed framework was applied to the EPID dynamic images of ten lung cancer patients, which included 183 frames (mean: 18.3 per patient). The 4D dose distributions during the treatment time were successfully obtained by applying the dose calculation algorithm to the simulated 4D "treatment" CT images. The mean±standard deviation (SD) of the percentage errors between the prescribed dose and the estimated dose at an isocenter for all cases was 3.25±4.43%. The maximum error for the ten cases was 14.67% (prescribed dose: 1.50Gy, estimated dose: 1.72Gy), and the minimum error was 0.00%. The proposed framework could be feasible for monitoring the 4D dose distribution and dose errors within a patient's body during treatment.

Feasibility study of automated framework for estimating lung tumor locations for target-based patient positioning in stereotactic body radiotherapy.

OBJECTIVE: To investigate the feasibility of an automated framework for estimating the lung tumor locations for tumor-based patient positioning with megavolt-cone-beam computed tomography (MV-CBCT) during stereotactic body radiotherapy (SBRT). METHODS: A lung screening phantom and ten lung cancer cases with solid lung tumors, who were treated with SBRT, were employed to this study. The locations of tumors in MV-CBCT images were estimated using a tumor-template matching technique between a tumor template and the MV-CBCT. Tumor templates were produced by cropping the gross tumor volume (GTV) regions, which were enhanced by a Sobel filter or a blob structure enhancement (BSE) filter. Reference tumor locations (grand truth) were determined based on a consensus between a radiation oncologist and a medical physicist. RESULTS: According to the results of the phantom study, the average Euclidean distances of the location errors in the original, Sobel-filtered, and BSE-filtered images were 2.0 ± 4.1 mm, 12.8 ± 9.4 mm, and 0.4 ± 0.5 mm, respectively. For clinical cases, these were 3.4 ± 7.1 mm, 7.2 ± 11.6 mm, and 1.6 ± 1.2 mm, respectively. CONCLUSION: The feasibility study suggests that our proposed framework based on the BSE filter may be a useful tool for tumor-based patient positioning in SBRT.

[Development of a new position-recognition system for robotic radiosurgery systems using machine vision].

CyberKnife(®) provides continuous guidance through radiography, allowing instantaneous X-ray images to be obtained; it is also equipped with 6D adjustment for patient setup. Its disadvantage is that registration is carried out just before irradiation, making it impossible to perform stereo-radiography during irradiation. In addition, patient movement cannot be detected during irradiation. In this study, we describe a new registration system that we term "Machine Vision," which subjects the patient to no additional radiation exposure for registration purposes, can be set up promptly, and allows real-time registration during irradiation. Our technique offers distinct advantages over CyberKnife by enabling a safer and more precise mode of treatment. "Machine Vision," which we have designed and fabricated, is an automatic registration system that employs three charge coupled device cameras oriented in different directions that allow us to obtain a characteristic depiction of the shape of both sides of the fetal fissure and external ears in a human head phantom. We examined the degree of precision of this registration system and concluded it to be suitable as an alternative method of registration without radiation exposure when displacement is less than 1.0 mm in radiotherapy. It has potential for application to CyberKnife in clinical treatment.

Acute urinary morbidity after a permanent 125I implantation for localized prostate cancer.

We evaluated the predictive factors of acute urinary morbidity (AUM) after prostate brachytherapy. From November 2005 to January 2007, 62 patients with localized prostate cancer were treated using brachytherapy. The (125)Iodine ((125)I) seed-delivering method was a modified peripheral pattern. The prescribed dose was 144 Gy. Urinary morbidity was scored at 3 months after implantation. The clinical and treatment parameters were analysed for correlation with AUM. In particular, in this study, Du90 (the minimal dose received by 90% of the urethra), Dup90 (the minimal dose received by 90% of the proximal half of the urethra on the bladder side) and Dud90 (the minimal dose received by 90% of the distal half of the urethra on the penile side) were analysed. We found that 43 patients (69.4%) experienced acute urinary symptoms at 3 months after implantation. Of them, 40 patients had Grade 1 AUM, one patient had Grade 2 pain, and two patients had Grade 2 urinary frequency. None of the patients had ≥Grade 3. Univariate and multivariate analysis revealed that Du90 and Dup90 were significantly correlated with AUM. In this study, Du90 and Dup90 were the most significant predictors of AUM after prostate brachytherapy.

Computer-assisted delineation of lung tumor regions in treatment planning CT images with PET/CT image sets based on an optimum contour selection method.

To assist radiation oncologists in the delineation of tumor regions during treatment planning for lung cancer, we have proposed an automated contouring algorithm based on an optimum contour selection (OCS) method for treatment planning computed tomography (CT) images with positron emission tomography (PET)/CT images. The basic concept of the OCS is to select a global optimum object contour based on multiple active delineations with a level set method around tumors. First, the PET images were registered to the planning CT images by using affine transformation matrices. The initial gross tumor volume (GTV) of each lung tumor was identified by thresholding the PET image at a certain standardized uptake value, and then each initial GTV location was corrected in the region of interest of the planning CT image. Finally, the contours of final GTV regions were determined in the planning CT images by using the OCS. The proposed method was evaluated by testing six cases with a Dice similarity coefficient (DSC), which denoted the degree of region similarity between the GTVs contoured by radiation oncologists and the proposed method. The average three-dimensional DSC for the six cases was 0.78 by the proposed method, but only 0.34 by a conventional method based on a simple level set method. The proposed method may be helpful for treatment planners in contouring the GTV regions.

Definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy for primary lung cancer.

AIM: To retrospectively evaluate the efficacy and safety of definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy (SBRT) for primary lung cancer. PATIENTS AND METHODS: Between April 2003 and December 2011, 398 patients with primary lung tumor underwent SBRT at the Kyushu University Hospital, and 46 out of these developed local recurrence after SBRT. Definitive fractionated re-irradiation was performed for 17 out of the 46 patients. The median dose of re-irradiation was 60 Gy/ 30 fractions. Concurrent chemotherapy was given to four patients. RESULTS: The median follow-up duration was 12.6 months. At one year post-re-irradiation, local progression-free survival was 33.8%; progression-free survival, 30.9%; cause-specific survival, 79.3%; and overall survival, 74.7%. No severe adverse events were observed during the follow-up. CONCLUSION: Definitive fractionated re-irradiation is thought to be a safe alternative therapy for local recurrence following SBRT, although its efficacy may be not entirely satisfactory.

Similar-case-based optimization of beam arrangements in stereotactic body radiotherapy for assisting treatment planners.

OBJECTIVE: To develop a similar-case-based optimization method for beam arrangements in lung stereotactic body radiotherapy (SBRT) to assist treatment planners. METHODS: First, cases that are similar to an objective case were automatically selected based on geometrical features related to a planning target volume (PTV) location, PTV shape, lung size, and spinal cord position. Second, initial beam arrangements were determined by registration of similar cases with the objective case using a linear registration technique. Finally, beam directions of the objective case were locally optimized based on the cost function, which takes into account the radiation absorption in normal tissues and organs at risk. The proposed method was evaluated with 10 test cases and a treatment planning database including 81 cases, by using 11 planning evaluation indices such as tumor control probability and normal tissue complication probability (NTCP). RESULTS: The procedure for the local optimization of beam arrangements improved the quality of treatment plans with significant differences (P < 0.05) in the homogeneity index and conformity index for the PTV, V10, V20, mean dose, and NTCP for the lung. CONCLUSION: The proposed method could be usable as a computer-aided treatment planning tool for the determination of beam arrangements in SBRT.

Treatment outcome of high-dose-rate interstitial radiation therapy for patients with stage I and II mobile tongue cancer.

OBJECTIVES: The aim of the study was to investigate the outcomes of high-dose-rate interstitial radiation therapy for patients with Stage I and II mobile tongue cancer retrospectively. METHODS: Sixty-seven patients with Stage I and II mobile tongue cancer were treated with high-dose-rate interstitial radiation therapy, with or without external beam radiation therapy, between 1997 and 2007. The median dose of interstitial radiation therapy was 50 Gy in 10 fractions over 6 days. Thirty-five patients received external beam radiation therapy before interstitial radiation therapy. The median dose of external beam radiation therapy was 20 Gy delivered with single-lateral or bilateral fields, including the primary tumor site and upper jugular lymph nodes. Thirty-seven patients received concurrent chemotherapy, including carboplatin, cisplatin, fluorouracil or tegafur, gimeracil and oteracil (TS-1) systemically or with intra-arterial injection. Thirty-three patients received intratumoral injection of bleomycin before catheter insertion. The median follow-up time was 58.6 months (range 15.1-102.4 months). RESULTS: The 5-year overall, cause-specific, progression-free survival rate and local control rate were 88.7, 92.1, 76.0 and 94.0%, respectively. Fourteen patients developed cervical lymph node recurrence, 11 of which were distributed within the external beam radiation therapy field. We found local failures in four cases within 2 years after the treatment and in three cases after >7 years, even though the latter were difficult to distinguish from second primary cancers. CONCLUSIONS: The treatment results of our institutions were equivalent to previous reports. Most cervical lymph node metastases occurred within the external beam radiation therapy field, which implied that the external beam radiation therapy dose of 20-30 Gy was insufficient to prevent late cervical lymph node metastases.

Postoperative radiotherapy in patients with salivary duct carcinoma: clinical outcomes and prognostic factors.

This study sought to investigate the clinical outcome and the role of postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who had undergone surgery and postoperative radiotherapy. We performed a retrospective analysis of 25 SDC patients treated between 1998 and 2011 with surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy (range, 49.5-61.4 Gy). The clinical target volume (CTV) was defined as the tumor bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the tumor bed and bilateral neck in six patients. Local control (LC), disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The 5-year LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found in 12 patients: seven as local, four as regional and eight as distant failure. Perineural and lymphovascular invasion was a significant prognostic factor for LC (P = 0.03). Local failure was common, and the presence of local recurrence significantly affected the OS (P < 0.05). We conclude that surgery and postoperative radiotherapy is expected to decrease the risk of local failure and contribute to good prognoses for patients with SDC. It might be advisable to have the CTV include the cranial nerves involved and the corresponding parts of the skull base in cases of pathologically positive perineural invasion.

Clinical results of stereotactic body radiotherapy for Stage I small-cell lung cancer: a single institutional experience.

The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for Stage I small-cell lung cancer (SCLC). From April 2003 to September 2009, a total of eight patients with Stage I SCLC were treated with SBRT in our institution. In all patients, the lung tumors were proven as SCLC pathologically. The patients' ages were 58-84 years (median: 74). The T-stage of the primary tumor was T1a in two, T1b in two and T2a in four patients. Six of the patients were inoperable because of poor cardiac and/or pulmonary function, and two patients refused surgery. SBRT was given using 7-8 non-coplanar beams with 48 Gy in four fractions. Six of the eight patients received 3-4 cycles of chemotherapy using carboplatin (CBDCA) + etoposide (VP-16) or cisplatin (CDDP) + irinotecan (CPT-11). The follow-up period for all patients was 6-60 months (median: 32). Six patients were still alive without any recurrence. One patient died from this disease and one died from another disease. The overall and disease-specific survival rate at three years was 72% and 86%, respectively. There were no patients with local progression of the lesion targeted by SBRT. Only one patient had nodal recurrence in the mediastinum at 12 months after treatment. The progression-free survival rate was 71%. No Grade 2 or higher SBRT-related toxicities were observed. SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer. However, further investigation is needed using a large series of patients.

Computer-aided beam arrangement based on similar cases in radiation treatment-planning databases for stereotactic lung radiation therapy.

The purpose of this study was to develop a computer-aided method for determination of beam arrangements based on similar cases in a radiotherapy treatment-planning database for stereotactic lung radiation therapy. Similar-case-based beam arrangements were automatically determined based on the following two steps. First, the five most similar cases were searched, based on geometrical features related to the location, size and shape of the planning target volume, lung and spinal cord. Second, five beam arrangements of an objective case were automatically determined by registering five similar cases with the objective case, with respect to lung regions, by means of a linear registration technique. For evaluation of the beam arrangements five treatment plans were manually created by applying the beam arrangements determined in the second step to the objective case. The most usable beam arrangement was selected by sorting the five treatment plans based on eight plan evaluation indices, including the D95, mean lung dose and spinal cord maximum dose. We applied the proposed method to 10 test cases, by using an RTP database of 81 cases with lung cancer, and compared the eight plan evaluation indices between the original treatment plan and the corresponding most usable similar-case-based treatment plan. As a result, the proposed method may provide usable beam arrangements, which have no statistically significant differences from the original beam arrangements (P > 0.05) in terms of the eight plan evaluation indices. Therefore, the proposed method could be employed as an educational tool for less experienced treatment planners.

Computerized estimation of patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy.

We have developed a computerized method for estimating patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy. The patient setup errors were estimated based on a template-matching technique that compared the portal image and a localized pelvic template image with a clinical target volume produced from a digitally reconstructed radiography (DRR) image of each patient. We evaluated the proposed method by calculating the residual error between the patient setup error obtained by the proposed method and the gold standard setup error determined by consensus between two radiation oncologists. Eleven training cases with prostate cancer were used for development of the proposed method, and then we applied the method to 10 test cases as a validation test. As a result, the residual errors in the anterior-posterior, superior-inferior and left-right directions were smaller than 2 mm for the validation test. The mean residual error was 2.65 ± 1.21 mm in the Euclidean distance for training cases, and 3.10 ± 1.49 mm for the validation test. There was no statistically significant difference in the residual error between the test for training cases and the validation test (P = 0.438). The proposed method appears to be robust for detecting patient setup error in the treatment of prostate cancer radiotherapy.

Radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy: risk factors and dose-volume relationship.

PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF.