Evaluation of robustness of optimization methods in breast intensity-modulated radiation therapy using TomoTherapy.

Intensity-modulated radiation therapy (IMRT) has become a popular choice for breast cancer treatment. We aimed to evaluate and compare the robustness of each optimization method used for breast IMRT using TomoTherapy. A retrospective analysis was performed on 10 patients with left breast cancer. For each optimization method (clipping, virtual bolus, and skin flash), a corresponding 50 Gy/25 fr plan was created in the helical and direct TomoTherapy modes. The dose-volume histogram parameters were compared after shifting the patients anteriorly and posteriorly. In the helical mode, when the patient was not shifted, the median D1cc (minimum dose delivered to 1 cc of the organ volume) of the breast skin for the clipping and virtual bolus plans was 52.2 (interquartile range: 51.9-52.6) and 50.4 (50.1-50.8) Gy, respectively. After an anterior shift, D1cc of the breast skin for the clipping and virtual bolus plans was 56.0 (55.6-56.8) and 50.9 (50.5-51.3) Gy, respectively. When the direct mode was used without shifting the patient, D1cc of the breast skin for the clipping, virtual bolus, and skin flash plans was 52.6 (51.9-53.1), 53.4 (52.6-53.9), and 52.3 (51.7-53.0) Gy, respectively. After shifting anteriorly, D1cc of the breast skin for the clipping, virtual bolus, and skin flash plans was 55.6 (54.1-56.4), 52.4 (52.0-53.0), and 53.6 (52.6-54.6) Gy, respectively. The clipping method is not sufficient for breast IMRT. The virtual bolus and skin flash methods were more robust optimization methods according to our analyses.

Respiratory motion tracking of spine stereotactic radiotherapy in prone position.

PURPOSE: The CyberKnife system is a specialized device for non-coplanar irradiation; however, it possesses the geometric restriction that the beam cannot be irradiated from under the treatment couch. Prone positioning is expected to reduce the dose to normal lung tissue in spinal stereotactic body radiotherapy (SBRT) owing to the efficiency of beam arrangement; however, respiratory motion occurs. Therefore, the Xsight spine prone tracking (XSPT) system is used to reduce the effects of respiratory motion. The purpose of this study was to evaluate the motion-tracking error of the spine in the prone position. MATERIALS AND METHODS: Data from all 25 patients who underwent spinal SBRT at our institution between April 2020 and February 2022 using CyberKnife (VSI, version 11.1.0) with the XSPT tracking system were retrospectively analyzed using log files. The tumor motion, correlation, and prediction errors for each patient were examined. Furthermore, to assess the potential relationships between the parameters, the relationships between the tumor-motion amplitudes and correlation or prediction errors were investigated using linear regression. RESULTS: The tumor-motion amplitudes in each direction were as follows: superior-inferior (SI), 0.51 ± 0.39 mm; left-right (LR), 0.37 ± 0.29 mm; and anterior-posterior (AP), 3.43 ± 1.63 mm. The overall mean correlation and prediction errors were 0.66 ± 0.48 mm and 0.06 ± 0.07 mm, respectively. The prediction errors were strongly correlated with the tumor-motion amplitudes, whereas the correlation errors were not. CONCLUSIONS: This study demonstrated that the correlation error of spinal SBRT in the prone position is sufficiently small to be independent of the tumor-motion amplitude. Furthermore, the prediction error is small, contributing only slightly to the tracking error. These findings will improve the understanding of how to compensate for respiratory-motion uncertainty in the prone position.

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

Fiducial marker position affects target volume in stereotactic lung irradiation.

PURPOSE: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage. MATERIALS AND METHODS: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (dex ) and inspiratory (din ) CT, and the ratio of the ITV/V(GTVex ), were investigated. RESULTS: Upon comparing each lobe, although there was no significant difference in the ddiff and the ITV/V(GTVex ) between all lobes for dex  < 10 mm, there was significant difference in the ddiff and the ITV/V(GTVex ) between the lower and upper lobes for dex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the ddiff and the ITV/V(GTVex ) between dex ≥10 mm and dex  < 10 mm in all lung regions (p < 0.05). CONCLUSION: The ITV that had no margin from GTVs increased when dex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage.

Survey of malignant pleural mesothelioma treatment in Japan: Patterns of practice and clinical outcomes in tomotherapy facilities.

We conducted a nationwide survey of tomotherapy for malignant pleural mesothelioma (MPM) in Japan. Fifty-six facilities were surveyed and data on 31 patients treated curatively between 2008 and 2017 were collected from 14 facilities. Twenty patients received hemithorax irradiation after extrapleural pneumonectomy (EPP) (first group). Five patients received irradiation without EPP (second group), while six received salvage radiotherapy for local recurrence (salvage group). Among the seven patients not undergoing EPP, five (four in the second group and one in the salvage group) were treated with lung sparing pleural irradiation (LSPI) and two with irradiation to visible tumors. Two-year overall survival (OS) rates in the first and second groups were 33% and 60%, respectively (median, 13 vs 30 months, P = 0.82). In the first and second groups, 2-year local control (LC) rates were 53 and 67%, respectively (P = 0.54) and 2-year progression-free survival (PFS) rates were 16% and 60%, respectively (P = 0.07). Distant metastases occurred in 15 patients in the first group and three in the second group. In the salvage group, the median OS was 18 months. Recurrence was observed in the irradiated volume in four patients. The contralateral lung dose was higher in LSPI than in hemithorax irradiation plans (mean, 11.0 ± 2.2 vs 6.1 ± 3.1 Gy, P = 0.002). Grade 3 or 5 lung toxicity was observed in two patients receiving EPP and hemithorax irradiation, but not in those undergoing LSPI. In conclusion, outcomes of EPP and hemithorax irradiation were not satisfactory, whereas LSPI appeared promising and encouraging.

Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.

Cytomegalovirus reactivation in esophageal cancer patients receiving chemoradiotherapy: A retrospective analysis.

BACKGROUND: Although rare, cytomegalovirus (CMV) reactivation can be lethal in patients with cancer. However, the criteria for the prevention of cytomegalovirus reactivation during cancer treatment are unclear. This study aimed to identify factors associated with CMV reactivation in patients with esophageal cancer who were receiving chemoradiotherapy. METHODS: This retrospective study included esophageal cancer patients receiving definitive or palliative chemoradiotherapy during April 2013-March 2020. Patients with fever during chemoradiotherapy underwent a systemic work-up to detect the primary focus of infection, and CMV antigenemia was assessed in cases of unidentifiable infection. RESULTS: Among 132 patients (80.3% male, median age 69 years [range, 39-86 years]), 124 received 5-fluorouracil plus cisplatin and 8 received oxaliplatin-5-fluorouracil-levofolinate chemotherapy. Overall, 19 patients had CMV reactivation, 37 had other infections, and 76 had no identified infection (groups 1, 2, and 3, respectively). Median minimum lymphocyte counts were 81.0/µl (interquartile range: 52.0-144.0/µl), 120.0/µl (81.0-162.5/µl), and 185.5/µl (120.5-328.0/µl) in groups 1, 2, and 3, respectively, with counts being significantly lower in groups 1 and 2 than in group 3 (p < 0.001). In multiple logistic regression analysis, the minimum lymphocyte count was associated with CMV reactivation (odds ratio 0.983, 95% confidence interval: 0.973-0.994, p = 0.002). CONCLUSION: CMV reactivation is not rare in patients with esophageal cancer who were receiving chemoradiotherapy and is associated with the minimum lymphocyte counts. CMV reactivation should be considered during differential diagnosis for patients with a severe decline in lymphocyte counts when receiving chemoradiotherapy.

The feasibility of transcatheter arterial chemoembolization following radiation therapy for hepatocellular carcinoma.

BACKGROUND: Technological developments have led to an increased usage of external-body radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) may be required later in patients treated with RT because of the high recurrence rate and multinodular presentation of HCC. However, despite the risk of liver function impairment, the cumulative liver damage correlated with TACE following a hepatic RT has not been adequately assessed. PURPOSE: To evaluate the feasibility of TACE following RT for HCC. MATERIALS AND METHODS: Sixty-seven patients with HCC who underwent TACE after RT were retrospectively evaluated between 2012 and 2018. We assessed increases in Child-Turcotte-Pugh (CTP) by ≥2 points at 1 month, the incidence of major complications, survival duration, and short-term mortality within 6 months after TACE. Furthermore, we evaluated the predictive factors for liver function impairment and short-term mortality. RESULTS: Eight patients experienced a CTP increase ≥2 points at 1 month. There were no cases of liver abscesses or bilomas. Nine patients died within 6 months following TACE. The mean liver dose (MLD) was a significant predictor of liver function impairment at 1 month (p = 0.042). Low liver functional reserve, distant metastasis (p = 0.037), MLD (p = 0.046), TACE type (p = 0.025), and TACE within 3 months following RT (p = 0.007) were significant predictors of short-term mortality. CONCLUSIONS: Despite the feasibility of TACE following RT, clinicians should pay attention to impaired pretreatment liver function, following high dose RT, and the short duration between RT and TACE.

Plan comparison of prostate stereotactic radiotherapy in spacer implant patients.

In prostate stereotactic body radiation therapy (SBRT), hydrogel spacers are increasingly used. This study aimed to perform a dosimetry comparison of treatment plans using CyberKnife (CK), commonly used for prostate SBRT, Helical TomoTherapy (HT), and TrueBeam (TB) in patients with hydrogel spacer implantations. The data of 20 patients who received hydrogel spacer implantation for prostate SBRT were retrospectively analyzed. The prescription dose was 36.25 Gy in five fractions to 95% of the planning target volume (PTV; D95). The conformity index (CI), gradient index (GI), homogeneity index (HI), and dose-volume histogram (DVH) were analyzed for the three modalities, using the same PTV margins. The monitor unit (MU) and the beam-on-time (BOT) values were subsequently compared. The CI of TB (0.93 ± 0.02) was significantly superior to those of CK (0.82 ± 0.03, p < 0.01) and HT (0.86 ± 0.03, p < 0.01). Similarly, the GI value of TB (3.59 ± 0.12) was significantly better than those of CK (4.31 ± 0.43, p < 0.01) and HT (4.52 ± 0.24, p < 0.01). The median doses to the bladder did not differ between the CK and TB (V18.1 Gy: 16.5% ± 4.5% vs. 15.8% ± 4.4%, p = 1.00), but were significantly higher for HT (V18.1 Gy: 33.2% ± 7.3%, p < 0.01 vs. CK, p < 0.01 vs. TB). The median rectal dose was significantly lower for TB (V18.1 Gy: 5.6% ± 4.5%) than for CK (V18.1 Gy: 11.2% ± 6.7%, p < 0.01) and HT (20.2% ± 8.3%, p < 0.01). TB had the shortest BOT (2.6 min; CK: 17.4 min, HT: 6.9 min). TB could create treatment plans dosimetrically comparable to those of CK when using the same margins, in patients with hydrogel spacers.

Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study.

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. MATERIALS AND METHODS: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. RESULTS: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. CONCLUSION: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.

Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours.

AIM: To investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours. BACKGROUND: In the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment. MATERIALS AND METHODS: Data were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment. RESULTS: The mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes. CONCLUSIONS: More caution and an additional safety margins are required when tracking a single fiducial marker.

Pattern of recurrence after CyberKnife stereotactic body radiotherapy for peripheral early non-small cell lung cancer.

BACKGROUND: The treatment efficacy after CyberKnife stereotactic body radiotherapy (SBRT) have not been adequately addressed. The purpose of this study was to investigate pattern of recurrence according to irradiation field after CyberKnife SBRT for early-stage non-small cell lung cancer (NSCLC). METHODS: This retrospective study included patients with peripheral cT1/2N0M0 NSCLC that was treated with SBRT using a CyberKnife between May 2013 and March 2016 at single institute and followed up by more than two imaging examinations. Both operable and inoperable patients were included. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method with 95% confidence intervals (CI). Cumulative incidence curves of recurrence were calculated and compared using the Gray's test. RESULTS: Total 71 patients were included and analyzed in this study. The median follow-up period for surviving patients was 34 months (range, 7-64 months). The 2-year OS and PFS rate were 93% (95% CI: 83-97%) and 77% (95% CI: 65-86%), respectively. The 2-year cumulative incidence rate of infield recurrence and out-of-field recurrence were 6% (95% CI: 2-14%) and 17% (95% CI: 9-27%), respectively. Gross tumor volume (GTV) ≥9 mL and diagnosis-to-treatment interval (DTI) ≥90 days were significantly associated with infield recurrence (P<0.001 and P=0.007), and epidermal growth factor receptor (EGFR) mutation was significantly associated with out-of-field recurrence (P=0.014). CONCLUSIONS: Treatment efficacy after CyberKnife SBRT for peripheral early-stage NSCLC was identical to previous conventional linac-based SBRT reports. With short follow-up period, it was found that GTV and DTI were the significant predictive factor of infield recurrence, and EGFR mutation was the significant predictive factor of out-of-field recurrence.

Additional chemotherapy improved local control and overall survival after stereotactic body radiation therapy for patients with oligo-recurrence.

BACKGROUND: Oligo-recurrence has been considered to confer improved prognosis than other oligometastatic conditions, and stereotactic body radiation therapy (SBRT) is considered as an option of local therapy for lung or liver metastases. The purpose of this study was to investigate the efficacy and safety of SBRT for lung and liver oligo-recurrent lesions and evaluate predictive factors for local control and prognosis. METHODS: This retrospective study included patients who presented with 1-3 matachronous lung or liver metastases, and treated with SBRT between May 2013 and March 2016 at a single institution. All patients harbored a controlled primary lesion. Patients with < 6 months of follow-up were excluded. Local control, progression free survival, and overall survival rates were analyzed according to the Kaplan-Meier product limit method. Univariable log-rank and multivariable Cox regression analyses were performed to clarify predictive factors for local control and prognosis. Toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Seventy-six patients with a total of 70 and 44 lung and liver lesions were included. The median follow-up period was 21 (range, 7-43) months. The 1-year local control, progression-free survival and overall survival rates were 89, 38 and 96%, respectively. Smaller gross tumor volume and additional chemotherapy after SBRT were significant predictive factors for better local control (p = 0.005 and p = 0.047), and the presence of a single metastatic lesion was a significant factor of good progression free survival (p = 0.008). Additional chemotherapy after SBRT was not a significant predictive factor but conferred to better overall survival (p = 0.078). Among colorectal cancer patients, post SBRT chemotherapy was significantly associated with better OS (p = 0.025). Over grade 3 adverse event was seen in only one patient. CONCLUSION: SBRT is a safe and effective treatment for patients with lung and liver oligo-recurrence. Additional chemotherapy after SBRT improved local control, and single metastatic lesion was a significant predictive factor of better PFS in this study. Among colorectal cancer patients, additional chemotherapy after SBRT significantly associated better OS.

Clinical log data analysis for assessing the accuracy of the CyberKnife fiducial-free lung tumor tracking system.

PURPOSE: The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems use a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the target's future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data. METHODS AND MATERIALS: Data from 211 fractions in 42 patients with lung tumors were analyzed. Log files produced by the CyberKnife Synchrony system were acquired after each treatment; the mean correlation and prediction errors for each patient were calculated. Additionally, we examined the tracking tumor-related parameters and analyzed the relationships between the model errors and tracking tumor-related parameters. RESULTS: The overall means ± standard deviations (SDs) of the correlation errors were 0.70 ± 0.43 mm, 0.36 ± 0.16 mm, 0.44 ± 0.22 mm, and 0.95 ± 0.43 mm for the superoinferior (SI), left-right (LR), anteroposterior (AP), and radial directions, respectively. The overall means ± SDs of the prediction errors were 0.13 ± 0.11 mm, 0.03 ± 0.02 mm, 0.03 ± 0.02 mm, and 0.14 ± 0.11 mm for the SI, LR, AP, and radial directions, respectively. There were no significant differences in these errors between the XLT and 1-View tracking methods. The tumor motion amplitude was moderately associated with the correlation error and strongly related to the prediction error in the SI and radial directions. CONCLUSIONS: Clinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination.

Investigation of the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy for brainstem metastases using a new evaluation criterion: 'symptomatic control'.

The treatment of brainstem metastases remains a challenge as the brainstem itself is considered a neurological organ at risk. We aimed to investigate the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy (HFSRT) for brainstem metastases, and to examine the balance between efficacy and safety for the management of neurological symptoms. A total of 26 lesions [pons (n = 18), medulla (n = 4) and midbrain (n = 4)] in 20 patients treated with CyberKnife hypofractionated stereotactic radiotherapy were retrospectively analyzed. The total radiation doses (18-30 Gy) were delivered in 3 or 5 equal fractions. The median follow-up was 6.5 (range, 0.5-38.0) months. The 6- and 12-month local control rates were 100% and 90%, respectively. Symptomatic failures, defined as the worsening and appearance of neurological symptoms due to the brainstem lesion after CyberKnife HFSRT, were observed in 6 patients [local failure (n = 1) and adverse events (n = 5). The symptomatic control and overall survival rates were 90% and 72% (after 6 months), respectively, and 76% and 53% (after 12 months), respectively. Longer symptomatic control was associated with site of lesion origin, and longer overall survival was associated with a graded prognostic assessment score of >2. To our knowledge, this is the second study to investigate the efficacy and safety of CyberKnife HFSRT for brainstem metastases. The local control rate was comparable with that of prior stereotactic radiosurgery studies. We propose a new evaluation criterion-'symptomatic control'-to evaluate the efficacy and safety of brainstem radiotherapy.

Identification of the suitable leaf margin for liver stereotactic body radiotherapy with flattening filter-free beams.

The purpose of this study is to identify the suitable leaf margin for liver stereotactic body radiotherapy (SBRT) with flattening filter-free (FFF) beams, as compared with that with flattening filter (FF) beams. SBRT treatment planning for 10 patients with liver cancer was performed using 10-MV FFF and FF beams obtained from a Varian TrueBeam (Varian Medical Systems, Palo Alto, CA) linear accelerator. Each plan was generated with the leaf margin to the planning target volume (PTV) ranging from -3 to 5 mm. The prescription dose at D95 (dose covering 95% of the volume) was 48 Gy in 4 fractions to the PTV. The following dosimetric parameters were evaluated quantitatively: homogeneity index (HI), conformity index (CI), gradient index (GI), the normal liver receiving a dose greater than or equal to 20 Gy (V20), and the mean normal liver dose. The HI for FFF and FF beams increased as the leaf margin decreased. The leaf margins that achieved the best CI and GI were 0.1 and -0.3 mm for FFF beams, and 0.1 and -0.9 mm for FF beams. The liver V20 and the mean liver dose reached their minimum values at leaf margins of -0.8 and 0.0 mm for FFF beams, and -0.8 and 0.0 mm for FF beams. The suitable leaf margin for SBRT planning did not differ significantly for FFF and FF beams. Our data showed that, for both FFF and FF beams, a leaf margin of 0 or -1 mm was optimal for liver SBRT planning in terms of both target coverage and normal tissue sparing.

Dosimetric factors predicting radiation pneumonitis after CyberKnife stereotactic body radiotherapy for peripheral lung cancer.

OBJECTIVE: The aims of this study were to investigate the frequency of symptomatic radiation pneumonitis (RP) after CyberKnife lung stereotactic body radiotherapy (SBRT) and to evaluate predictive factors of symptomatic RP. METHODS: 56 patients with peripheral non-small-cell lung cancer were treated using the CyberKnife® VSI™ System (Accuracy Inc., Sunnyvale, CA) between May 2013 and September 2015. Total radiation doses ranged from 48 to 56 Gy, as delivered in four equal fractions. Symptomatic RP was defined as a grade of ≥2. Predictive factors for symptomatic RP were evaluated using univariate and multivariate analyses. RESULTS: With a median follow-up duration of 12.5 months (range, 3-27 months), symptomatic RP was observed in 6 (10.7%) of the 56 patients. In the univariate analysis, percent vital capacity (p < 0.05), maximum tumour diameter (p < 0.05), gross tumour volume (p < 0.05), planning target volume (p < 0.01), mean lung dose (p < 0.01) and a normal lung volume receiving 5-50 Gy of radiation (V5-50) (p < 0.01) were identified as significant predictive factors for symptomatic RP. In the multivariate analysis, only a V25 >3.4% (p = 0.011) was identified as a significant predictive factor of symptomatic RP. CONCLUSION: The incidence of symptomatic RP after CyberKnife SBRT was almost identical to the incidences reported in the linear accelerator-based SBRT. A significant association was observed between a V25 >3.4% and the risk of developing symptomatic RP. Advances in knowledge: This is the first report that has investigated prognostic factors for symptomatic RP after CyberKnife SBRT for lung cancer. The newly developed scoring system may help to predict symptomatic RP.

Efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis/inferior vena cava tumor thrombosis: evaluation by comparison with conventional three-dimensional conformal radiotherapy.

This study aimed to evaluate the efficacy of stereotactic body radiotherapy (SBRT) compared with three-dimensional conformal radiotherapy (3DCRT). Forty-three patients with portal vein tumor thrombosis (PVTT)/inferior vena cava tumor thrombosis (IVCTT) treated with SBRT (27 with CyberKnife (CK) and 16 with TrueBeam (TB)) from April 2013 to December 2014, and 54 treated with 3DCRT from June 2008 to March 2013 were evaluated. Dosimetric parameters, response to radiotherapy (RT) and survival outcomes were compared in total SBRT vs. 3DCRT, CK vs. 3DCRT and TB vs. 3DCRT, respectively. The median biologically effective dose 10 (BED10) values in total SBRT, CK, TB and 3DCRT were 73.4 Gy10, 75.0 Gy10, 60.5 Gy10 and 58.5 Gy10, respectively (P < 0.001 in total SBRT vs. 3DCRT, P < 0.001 in CK vs. 3DCRT, P = 0.004 in TB vs. 3DCRT). The tumor response rates were 67%, 70%, 62% and 46%, respectively (P = 0.04, P = 0.04, P = 0.25). The 1-year overall survival rates were 49.3%, 56.7%, 38.1% and 29.3%, respectively (P = 0.02, P = 0.02, P = 0.30), and the 1-year local progression rates were 20.4%, 21.9%, 18.8% and 43.6%, respectively (P = 0.01, P = 0.04, P = 0.10). The use of SBRT made it possible to achieve a higher BED10 compared with the use of 3DCRT. Improvements in local control and survival were achieved in the CK group and the total SBRT group. Our results suggest that SBRT may have the potential to be the standard RT technique for the treatment of PVTT/IVCTT.

Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma.

BACKGROUND: There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. METHODS: The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. RESULTS: There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. CONCLUSION: There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma, especially of diffuse large B-cell lymphoma.

Inverse planning for combination of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V100 achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D100 was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D90 was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D2cm(3): 408 ± 71 cGy vs manual optimization D2cm(3): 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D2cm(3): 452 ± 60 cGy vs manual optimization D2cm(3): 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.