Ten years outcomes after SABR in central and ultracentral primary lung tumors.

PURPOSE: SABR performed for central and ultracentral lung tumors is associated with increased toxicity but limited data is available on late toxicities. We studied toxicity in patients followed-up ≥ 2 years post-SABR at a single-institution. METHODS: All patients were treated using VMAT for a primary or recurrent central lung cancer between 2008-2015. 60 Gy was delivered in 8 or 12 fractions. Grade ≥ 3 clinical and radiological bronchial toxicity was scored. Multivariable Cox regression models were used to estimate hazard ratios. RESULTS: Of 127 eligible patients, 63% were treated with 8 fractions. Median tumor diameter was 4.4 cm (range 1.3-12.0). Median overall survival was 25.0 months (95% CI 16.5-33.5); 4% developed isolated local recurrences. The actuarial 5-year rate for severe clinical toxicity was 34.1% (95% CI 21.2-44.9). Both clinical toxicity and fatal lung haemorrhage were most observed when tumors were located ≤ 1 cm from the trachea or main bronchi (46% of all cases). The 5-year actuarial rate of radiological bronchial toxicity was 37.5% (95% CI 21.5-50.2). Multivariable analysis revealed that a performance score of 2 or 3 (HR 3.6; 95% CI 1.7-7.8), and tumor location ≤ 1 cm from the trachea or main bronchi (HR 4.3; 95% CI 1.2-14.9) were significant predictors for severe clinical toxicity. CONCLUSION: The actuarial rates for both severe clinical and radiological bronchial toxicity after central SABR was approximately 35% in patients surviving 5 years. Patients with tumors located ≤ 1 cm from the trachea or main bronchus were at the highest risk for severe clinical toxicity.

Local control and toxicity after magnetic resonance imaging (MR)-guided single fraction lung stereotactic ablative radiotherapy.

PURPOSE: Magnetic resonance imaging (MR)-guided radiotherapy permits continuous intrafraction visualization and use of automatic triggered beam delivery, with use of smaller planning target volumes (PTV). We report on long-term clinical outcomes following MR-guided single fraction (SF) lung SABR on a 0.35 T linac. MATERIALS AND METHODS: Details of patients treated with SF-SABR for lung tumors were accessed from an ethics approved institutional database. A breath-hold 3D MR simulation scan was performed using a true FISP sequence, followed by a breath-hold 3D CT scan. The gross tumor volume (GTV) was first contoured on the breath-hold CT scan, which was then compared with contours on the 3D MR scan, before the GTV was finalized. SABR plans used step-and-shoot IMRT beams to a PTV derived by adding a 5 mm margin to the breath-hold GTV, and a 3 mm gating window was used. SABR was delivered during repeated breath-holds, using automatic beam gating with continuous visualization of the GTV in a sagittal MR plane. RESULTS: Between 2018-2022, 50 consecutive patients were treated, and 69% had a primary non-small cell lung cancer. Median PTV was 11.2 cc (range 3.9-53.5); 80% of GTV's were located ≤2.5 cm from the chest wall. Prescribed doses were 34 Gy (in 58%), 30 Gy (32%), or between 20-28 Gy (10%). After a median follow-up of 18.1 months (95% CI 12.8-23.5), the 2-year survival was 82% (89% for primary NSCLC and 62% for metastases). After a median follow-up of 16.1 months (95% CI 11.2-21.1), local recurrences developed in 2 patients (4%). The 3-year local control rate was 97%, and just 1 patient developed grade ≥3 toxicity (chest wall pain). CONCLUSION: MR-guided SF-SABR delivery to lung tumors on a 0.35 T linac, using repeated breath-holds with automatic beam gating, achieves good tumor control and low toxicity.

Knowledge-Based Planning for Identifying High-Risk Stereotactic Ablative Radiation Therapy Treatment Plans for Lung Tumors Larger Than 5 cm.

PURPOSE: Stereotactic ablative body radiation therapy (SABR) for lung tumors ≥5 cm can be associated with more toxicity than that for smaller tumors. We investigated the relationship between dosimetry and toxicity and used a knowledge-based planning solution to retrospectively perform individualized treatment plan quality assurance (QA) with the aim of identifying where planning could have been improved. METHODS AND MATERIALS: Previous retrospective analysis of 53 patients with primary or recurrent non-small cell lung cancer ≥5 cm, treated with 5- or 8-fraction volumetric modulated arc therapy SABR between 2008 and 2014, showed 30% with grade ≥3 toxicity. During this period, several improvements were made to departmental planning protocols. RapidPlan was used to compare dosimetry of patients with or without grade ≥3 toxicity. A model comprising plans from patients without toxicity and compliant with the current planning protocol was used to provide QA for the plans from patients who had toxicity. RESULTS: Sixteen of 53 patients had grade ≥3 toxicity, including 10 with radiation pneumonitis (RP), 3 with lung hemorrhage (1 of these also had RP), and 1 with airway stenosis/atelectasis. RP was again shown to be significantly correlated with contralateral and total-lung V5 and mean lung dose. The 4 highest contralateral-lung doses belonged to patients with RP. Five of 10 clinical plans in patients with RP had a contralateral-lung mean dose up to 2.5 times higher than that of the knowledge-based plan. For 2 of 3 patients with lung hemorrhage and 1 with airway stenosis/atelectasis, the clinical plans had the highest proximal bronchial tree doses, which was also higher than in plans from the model. In 8 patients with grade ≥3 toxicity, clinical plans had dosimetry similar to that in the predictions from the model. CONCLUSIONS: A "no-toxicity" RapidPlan model identified the potential for dosimetric improvement in nearly 50% of historical treatment plans from patients with grade ≥3 toxicity after SABR for lung tumors ≥5 cm. Model-based QA may be useful for benchmarking treatment planning protocols in routine practice and in clinical studies.

Use of Stereotactic Ablative Radiotherapy (SABR) in Non-Small Cell Lung Cancer Measuring More Than 5 cm.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) is currently not the guideline-recommended treatment for lung tumors measuring more than 5 cm. However, improvements in radiotherapy techniques have led to increasing use of SABR for larger tumors. METHODS: We analyzed the clinical outcomes in patients with a primary or recurrent NSCLC measuring more than 5 cm and treated with five or eight fractions of SABR at our center. Patients who had prior thoracic radiotherapy were excluded. RESULTS: A total of 63 consecutive patients with a median tumor diameter of 5.8 cm (range 5.1-10.4) were identified; 81% had T2N0 disease and 18% had T3N0 disease. The median Charlson comorbidity index was 2 (range 0-6). After a median follow-up of 54.7 months, median survival was 28.3 months. Disease-free survival at 2 years was 82.1%, and the local, regional, and distant control rates at 2 years were 95.8%, 93.7%, and 83.6%, respectively. An out-of-field distant recurrence at one or more sites was the most common pattern of failure (10%). Grade 3 or higher toxicity was recorded in 30% of patients, with radiation pneumonitis being the most common toxicity (19%). A likely (n = 4) or possible (n = 8) treatment-related death was scored in 19% of patients. There was preexisting interstitial lung disease in eight patients (13%), with fatal toxicity developing in five of them (63%). CONCLUSIONS: Lung SABR in tumors larger than 5 cm resulted in high local control rates and acceptable survival outcomes in a patient population with appreciable comorbidity. Patients with interstitial lung disease should be considered a very high-risk population for SABR.

Optimizing SABR delivery for synchronous multiple lung tumors using volumetric-modulated arc therapy.

BACKGROUND: Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. MATERIAL AND METHODS: Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. RESULTS: Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gy of ≥6.5% (in 2Gy/fraction equivalent) (p = .007). CONCLUSION: Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions.

Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cancer.

INTRODUCTION: We defined "ultracentral" lung tumors as centrally located non-small cell lung cancers with planning target volumes overlapping the trachea or main bronchi. Increased toxicity has been reported after both conventional and stereotactic radiotherapy for such lesions. We studied outcomes after 12 fractions of 5 Gy (BED10 = 90 Gy, heterogeneous dose distribution) to ultracentral tumors in patients unfit for surgery or conventional chemoradiotherapy. METHODS: Clinical outcomes and dosimetric details were analyzed in 47 consecutive patients with single primary or recurrent ultracentral non-small cell lung cancer treated between 2010 and 2015. Those irradiated previously or with metastasis to sites other than the brain and adrenal glands were excluded. Treatments were delivered using volumetric modulated arc therapy. RESULTS: The median age was 77.5 years, 49% of patients had a World Health Organization performance score of 2 or higher, and the median planning target volume was 104.5cm(3) (range 17.7-508.5). At a median follow-up of 29.3 months, median overall survival was 15.9 months, and 3-year survival was 20.1%. No isolated local recurrences were observed. Grade 3 or higher toxicity was recorded in 38% of patients, with 21% scored as having a "possible" (n = 2) or "likely" (n = 8) treatment-related death between 5.2 and 18.2 months after treatment. Fatal pulmonary hemorrhage was observed in 15% of patients. CONCLUSIONS: Unfit patients with ultracentral tumors who were treated using this scheme had a high local control and a median survival of 15.9 months. Despite manifestation of rates of a fatal lung bleeding comparable to those seen with conventional radiotherapy for endobronchial tumors, the overall rate of G5 toxicity is of potential concern. Additional work is needed to identify tumor and treatment factors related to hemorrhage.

Use of physical restraints in Dutch intensive care units: a prospective multicenter study.

BACKGROUND: Increasing evidence indicates that harmful effects are associated with the use of physical restraint. OBJECTIVES: To characterize the use of physical restraint in intensive care units. Prevalence, adherence to protocols, and correlates of the use of physical restraint were determined. For comparisons between ICUs, adjustments were made for differences in patients' characteristics. METHODS: A prospective, cross-sectional, observational multicenter study with a representative sample (n = 25) of all Dutch intensive care units, ranging from local hospitals to academic centers. Each unit was visited twice, and all 379 patients admitted during these visits were included and were examined for use of physical restraint. RESULTS: Physical restraint was used in 23% of all patients (range, 0%-56% for different units). Of all 346 nurses interviewed, 31% reported using a protocol when applying physical restraint. When corrections were made for clustering within units, the risk for use of physical restraint was increased in patients with delirium or coma, in patients who could not communicate verbally, and in patients receiving psychoactive or sedative medications. Sex, severity of illness, and nurse to patient ratio were not independently related to use of physical restraint. In 11 units (44%), use of physical restraint was more frequent than expected on the basis of patients' characteristics, although this finding was not significant. CONCLUSIONS: Physical restraint is frequently used in Dutch intensive care units. The differences in frequency between units suggest that opportunities exist to limit the use of physical restraint.

Stereotactic ablative radiotherapy (SABR) for central lung tumors: Plan quality and long-term clinical outcomes.

BACKGROUND AND PURPOSE: Central lung SABR is less established due to toxicity concerns. We describe plan quality and clinical outcomes for patients treated with VMAT SABR using 8×7.5Gy. MATERIALS AND METHODS: We studied 80 consecutive patients with primary NSCLC and PTV ⩽2cm from the proximal bronchial tree (PBT), treated between 2008 and 2013. Dosimetric data were compared with institutional guidelines and study protocols, and long-term clinical outcomes were analyzed. RESULTS: PTV V95% was 60Gy in 96% of patients. Dmax was ⩾60Gy in 40% of patients for PBT, 26.3% for aorta, 55% for heart, and 1.3% for trachea. Esophageal maximum Dmax was 58Gy. Mean lung V5Gy/V20Gy was 21/8%. 54 patients (68%) exceeded RTOG0813 Dmax for ⩾1 organ-at-risk (OAR), with 27 exceeding PBT Dmax. 5 of 78 patients (6.4%) with adequate follow-up information had grade 3 toxicity. Grade 4 toxicity was not observed. Treatment-related death was considered possible (n=3) or likely (n=3) in 6 patients (7.5%). With median follow-up of 47months, 3-year survival was 53%, compared with 57% for 252 peripheral tumors treated with 3/5-fractions SABR in the same period (p=0.369). CONCLUSIONS: Although a substantial proportion of central SABR patients received ⩾60Gy to OARs, the 3-year survival was no different from peripheral SABR.

Mechanism, assessment, and incidence of male infertility after inguinal hernia surgery: a review of the preclinical and clinical literature.

BACKGROUND: The treatment of inguinal hernia has changed considerably over the past 15 years. We reviewed the preclinical and clinical literature to find out the effect of inguinal hernia surgery on male fertility because it has been suggested that hernia surgery may impair testicular function and male fertility. DATA SOURCES: A search on Embase, MEDLINE, and the Cochrane Library was performed to find related articles. CONCLUSIONS: Animal models show substantial effects of hernia repair on the structures in the spermatic cord, which is more pronounced in mesh repairs. Although the number of studies and the included numbers of patients were limited, clinical studies indicate that these potential adverse effects do not seem to have a clinical impact on male fertility in humans with inguinal hernias. Future clinical studies, preferably with bilateral patients, are necessary to investigate the clinical relevance of the effects of inguinal hernia and hernia surgery on male fertility.