Dislocation is a Leading Cause of Decreased Survival Rate in Primary Total Hip Arthroplasty Performed by Low-Volume Surgeons: Long-Term Retrospective Cohort Study.

BACKGROUND: This study aimed to evaluate the complications and long-term survival of primary total hip arthroplasty (THA) performed by low-volume (LV) surgeons at a LV hospital. We also determined the relationship between complications and revisions. METHODS: This retrospective cohort study included 220 THAs in 194 patients treated at our institution between 1998 and 2008, who received a minimum of a 10-year follow-up. The median annual THA volume at this hospital was 23 procedures (range, 11-32), and the annual volume per surgeon ranged from 1 to 19. We investigated the 90-day mortality and rates of periprosthetic joint infections, dislocations, and periprosthetic fractures up to the last visit (median follow-up, 11.8 years). Kaplan-Meier survival was calculated with revision as the end point. RESULTS: Postoperative infections, dislocations, and fractures at any time during the follow-up period were reported for 1 hip (0.5%), 23 hips (9.8%), and 4 hips (1.8%), respectively. One death occurred within the first 90 days postoperatively. Fifteen hips required revision surgery, and the survival rate was 95.5% at 5 years and 94.1% at 10 years. Of 10 hips that required early revision surgery within 5 years after the index surgery, 9 were revisions to address recurrent dislocation. CONCLUSION: The risk of dislocation was high. A high number of patients who underwent THA by LV surgeons required early revision because of dislocation. To achieve optimal long-term survivorship, LV surgeons should consider measures to reduce the risk of dislocation.

A low-volume surgeon is an independent risk factor for leg length discrepancy after primary total hip arthroplasty: a case-control study.

PURPOSE: Leg length discrepancy (LLD) is one of the bothersome complications that reduce patient satisfaction after total hip arthroplasty (THA). This study aimed to investigate the independent risk factors of LLD after primary THA. METHODS: This is a case-control study of 163 THAs for 163 patients at our institution between April 2015 and March 2018. The relevant data about the general characteristics of the patients (age, sex, body mass index, and diagnosis), surgery (surgical approach, type of femoral stem fixation, and surgeon volume), and radiological findings (Dorr classification and pre-operative LLD) were reviewed to identify the risk factors of ≥ 5 mm post-operative LLD according to radiological measurement and to calculate odds ratios (OR) via logistic regression analysis. RESULTS: The median (interquartile) absolute value of post-operative LLD was 3.9 (2.3-7.4) mm, and 57 (35.0%) patients had LLD of ≥ 5 mm. After controlling for possible confounders, a low-volume surgeon was considered the only independent risk factor of post-operative LLD (adjusted OR: 8.26; 95% confidence interval: 3.48, 19.60; P < 0.001). Among the 103 patients performed by high-volume surgeons, 82 (79.6%) had LLD of < 5 mm, whereas among the 60 patients performed by low-volume surgeons, only 24 (40.0%) achieved LLD of < 5 mm (P < 0.001). CONCLUSION: A low-volume surgeon is associated with an increased risk of a post-operative LLD after primary THA, and the importance of measurements should be recognized to prevent post-operative LLD and achieve optimal outcomes. Moreover, surgeons must inform patients about the risk of developing LLD pre-operatively.

Pretreatment C-reactive protein level predicts outcome and patterns of failure after chemoradiotherapy for locally advanced pancreatic cancer.

OBJECTIVES: In this study we evaluated the predictive value of pretreatment C-reactive protein (CRP) levels on patterns of failure and survival outcomes in patients with locally advanced pancreatic cancer (LAPC) who received chemoradiotherapy (CRT). METHODS: Data from 65 patients who underwent CRT for LAPC from July 2001 to May 2013 were retrospectively collected. Factors, including age, gender, Eastern Cooperative Oncology Group performance status (PS), histological confirmation, tumor size, tumor location, biliary drainage, stage, induction chemotherapy, CRP levels, neutrophil-to-lymphocyte ratio, platelet-lymphocyte ratio, albumin and carbohydrate antigen 19-9, were evaluated with regard to overall survival (OS) and patterns of failure using a Cox proportional hazards model. RESULTS: The 1-year OS and median follow-up for all of the patients were 63.9% and 15.2 months, respectively. The median survival time and 1-year OS were 18.0 months and 72.5%, respectively, in the patients with lower CRP levels (≤3.0 mg/L), whereas 11.0 months and 30.8%, respectively, in the patients with higher CRP levels (>3.0 mg/L). Thirty-seven patients had tumor recurrence after CRT. All of the patients with higher CRP levels developed distant metastases as a primary sign of treatment failure. In a multivariate analysis, higher CRP levels were significantly correlated with distant disease-free survival (p = 0.004, HR = 4.50) and OS (p = 0.004, HR = 3.001). By contrast, local progression-free survival was not significantly different between the CRP subgroups. CONCLUSION: The CRP levels were a significant predictor of survival and distant disease control for the LAPC patients who received CRT.

Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

Acute adverse events of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for early breast cancer in Japan: an interim analysis of the multi-institutional phase II UPBEAT study.

BACKGROUND: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. METHODS: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. RESULTS: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. CONCLUSIONS: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

Postoperative Intensity-Modulated Radiation Therapy for Myoepithelial Carcinoma in the Parotid Gland.

Myoepithelial carcinoma (MC) is an extremely rare form of tumor, with no standard treatment established to date. Although several reports have discussed postoperative radiation therapy (PORT), few have applied intensity-modulated radiation therapy (IMRT), and none has described the dose and radiation field in detail. In this report, we describe a case of MC of the parotid gland that was treated with high-dose IMRT (70 Gy) after partial resection. The patient, a 61-year-old female, underwent excisional surgery and was diagnosed with MC arising from a pleomorphic adenoma (PA). Postoperative irradiation was administered as 70 Gy in 35 fractions of local radiation. The patient had cancer recurrence in the irradiated field. However, no serious adverse events associated with the radiation therapy have been confirmed, implying that postoperative high-dose radiation therapy may be safely administered via IMRT.

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab.

INTRODUCTION: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors. MATERIALS AND METHODS: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP. RESULTS: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007). CONCLUSION: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma.

BACKGROUND: It is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC. METHODS: We retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed. RESULTS: Fifteen patients received treatment during the study period. The median age was 78 years (range 75-86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0-1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3-36.8] and 13.5 (95% CI 6.4-20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50-93.1%) and 66.7% (95% CI 37.5-84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4-36.8) and 14.9 (95% CI 7.0-20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6-89.1%) and 66.7% (95% CI 37.5-84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4-5 non-haematologic acute or late toxicities were not observed. CONCLUSIONS: The OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Study on the generation of perfluorooctane sulfonate from the aqueous film-forming foam.

Perfluorooctane sulfonate (C(8)HF(17)SO(3)) and perfluorooctane acid (C(8)HF(15)O(2)) are artificial chemicals and have been used all over the world, mainly as water repellent agents, fluorochemical surfactants, coating agents, etc. However, perfluorooctane sulfonate and perfluorooctane acid are environmental contaminants because of their stability, bio-accumulativeness, and long-term persistence in the ecological environment. At the present day, they are diffused all over the world. Lately, this diffusion is viewed with suspicion and there is a movement towards their restriction, even if the environmental fate of them is still under investigation. Fluorochemical surfactants are key compounds in the aqueous film-forming foam (AFFF) formulations. AFFFs are used for massive conflagration such as industrial fire and petroleum fire because of their efficient fire control. On the other hand, a lot of AFFFs are used in case of massive conflagration and most of them enter ocean and groundwater. Actually, perfluorooctane sulfonate and perfluorooctane sulfonate related substances were detected from the fire-fighting facility of US forces. Therefore, there is the possibility of generating perfluorooctane sulfonate and perfluorooctane sulfonate related substances from fluorochemical surfactants in the AFFFs. In this study, activated sludge added AFFF were analyzed for perfluorooctane sulfonate and perfluorooctane acid with time. And the perfluorooctane sulfonate was directly detected after 2 days using LC-MS. This shows that AFFF can be decomposed perfluorooctane sulfonate by microorganisms easily. However, perfluorooctane sulfonate would not decompose at all. Additionally, activated sludge added N-polyoxyethylene-N-propyl perfluorooctane sulfonamide which is one of the fluorochemical surfactants used in the AFFF was analyzed for perfluorooctane sulfonate and perfluorooctane acid with time and the perfluorooctane sulfonate was detected too.

Evaluation of Dynamic Tumor-tracking Intensity-modulated Radiotherapy for Locally Advanced Pancreatic Cancer.

Intensity-modulated radiotherapy (IMRT) is now regarded as an important treatment option for patients with locally advanced pancreatic cancer (LAPC). To reduce the underlying tumor motions and dosimetric errors during IMRT as well as the burden of respiratory management for patients, we started to apply a new treatment platform of the dynamic tumor dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT) using the gimbaled linac, which can swing IMRT toward the real-time tumor position under patients' voluntary breathing. Between June 2013 and March 2015, ten patients were treated, and the tumor-tracking accuracy and the practical benefits were evaluated. The mean PTV size in DTT-IMRT was 18% smaller than a conventional ITV-based PTV. The root-mean-squared errors between the predicted and the detected tumor positions were 1.3, 1.2, and 1.5 mm in left-right, anterior-posterior, and cranio-caudal directions, respectively. The mean in-room time was 24.5 min. This high-accuracy of tumor-tracking with reasonable treatment time are promising and beneficial to patients with LAPC.

Comparative evaluation of respiratory-gated and ungated FDG-PET for target volume definition in radiotherapy treatment planning for pancreatic cancer.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of respiratory-gated positron emission tomography (4D-PET) in pancreatic cancer radiotherapy treatment planning (RTTP). MATERIALS AND METHODS: Fourteen patients with 18F-fluorodeoxyglucose (FDG)-avid pancreatic tumours were evaluated between December 2013 and March 2015. Two sets of volumes were contoured for the pancreatic tumour of each patient. The biological target volume in three-dimensional RTTP (BTV3D) was contoured using conventional respiratory un-gated PET. The BTV3D was then expanded using population-based margins to generate a series of internal target volume 3D (ITV3D) values. The ITV 4D (ITV4D) was contoured using 4D-PET. Each of the five phases of 4D-PET was used for 4D contouring, and the ITV4D was constructed by summing the volumes defined on the five individual 4D-PET images. The relative volumes and normalized volumetric overlap were computed between ITV3D and ITV4D. RESULTS: On average, the FDG-avid tumour volumes were 1.6 (range: 0.8-2.3) fold greater in the ITV4D than in the BTV3D. On average, the ITV3D values were 2.0 (range: 1.1-3.4) fold larger than the corresponding ITV4D values. CONCLUSION: The ITV generated from 4D-PET can be used to improve the accuracy or reduce normal tissue irradiation compared with conventional un-gated PET-based ITV.

Initial characterization, dosimetric benchmark and performance validation of Dynamic Wave Arc.

BACKGROUND: Dynamic Wave Arc (DWA) is a clinical approach designed to maximize the versatility of Vero SBRT system by synchronizing the gantry-ring noncoplanar movement with D-MLC optimization. The purpose of this study was to verify the delivery accuracy of DWA approach and to evaluate the potential dosimetric benefits. METHODS: DWA is an extended form of VMAT with a continuous varying ring position. The main difference in the optimization modules of VMAT and DWA is during the angular spacing, where the DWA algorithm does not consider the gantry spacing, but only the Euclidian norm of the ring and gantry angle. A preclinical version of RayStation v4.6 (RaySearch Laboratories, Sweden) was used to create patient specific wave arc trajectories for 31 patients with various anatomical tumor regions (prostate, oligometatstatic cases, centrally-located non-small cell lung cancer (NSCLC) and locally advanced pancreatic cancer-LAPC). DWA was benchmarked against the current clinical approaches and coplanar VMAT. Each plan was evaluated with regards to dose distribution, modulation complexity (MCS), monitor units and treatment time efficiency. The delivery accuracy was evaluated using a 2D diode array that takes in consideration the multi-dimensionality of DWA during dose reconstruction. RESULTS: In centrally-located NSCLC cases, DWA improved the low dose spillage with 20 %, while the target coverage was increased with 17 % compared to 3D CRT. The structures that significantly benefited from using DWA were proximal bronchus and esophagus, with the maximal dose being reduced by 17 % and 24 %, respectively. For prostate and LAPC, neither technique seemed clearly superior to the other; however, DWA reduced with more than 65 % of the delivery time over IMRT. A steeper dose gradient outside the target was observed for all treatment sites (p < 0.01) with DWA. Except the oligometastatic cases, where the DWA-MCSs indicate a higher modulation, both DWA and VMAT modalities provide plans of similar complexity. The average É£ (3 % /3 mm) passing rate for DWA plans was 99.2 ± 1 % (range from 96.8 to 100 %). CONCLUSIONS: DWA proven to be a fully functional treatment technique, allowing additional flexibility in dose shaping, while preserving dosimetrically robust delivery and treatment times comparable with coplanar VMAT.

Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. RESULTS: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). CONCLUSIONS: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

The impact of abdominal compression on outcome in patients treated with stereotactic body radiotherapy for primary lung cancer.

The aim of this study was to evaluate the impact of abdominal compression (AC) on outcome in patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer. We retrospectively reviewed data for 47 patients with histologically proven non-small cell lung cancer and lung tumour motion ≥ 8 mm treated with SBRT. Setup error was corrected based on bony structure. The differences in overall survival (OS), local control (LC) and disease-free survival (DFS) were evaluated to compare patients treated with AC (n = 22) and without AC (n = 25). The median follow-up was 42.6 months (range, 1.4-94.6 months). The differences in the 3-year OS, LC and DFS rate between the two groups were not statistically significant (P = 0.909, 0.209 and 0.639, respectively). However, the largest difference was observed in the LC rate, which was 82.5% (95% CI, 54.9-94.0%) for patients treated without AC and 65.4% (95% CI, 40.2-82.0%) for those treated with AC. After stratifying the patients into prognostic groups based on sex and T-stage, the LC difference increased in the group with an unfavourable prognosis. The present study suggests that AC might be associated with a worse LC rate after SBRT using a bony-structure-based set-up.