Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients

Objective:To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer.Methods:37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS).Results:Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/β ratio 10  Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity.Conclusion:SBRT was effective and safe in lung cancer adrenal metastases. A dose–response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies.Advances in knowledge:SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.     

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Objective:

The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC).

Methods:

21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded.

Results:

The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V_50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V_60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V_20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V_40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: D_max, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6–33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%.

Conclusion:

SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine.

Advances in knowledge:

Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.     

Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas

Objectives:To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients.Methods:We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I–IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit.Results:Among 45 consecutively enrolled patients with a median age of 68 years (range 22–86), 26 (58%) were female. Thirty-one patients (69%) with a stage I–II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect.Conclusions:LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years.Advances in knowledge:This study shows the efficacy of LDRT in the treatment of MALT and MZL.     

Dosimetric benefits of hemigland stereotactic body radiotherapy for prostate cancer: implications for focal therapy

Objective:

Compared with standard, whole-gland (WG) therapies for prostate cancer, focal approaches may provide equivalent oncologic outcomes with fewer adverse effects. The purpose of this study was to compare organ-at-risk (OAR) dosimetry between hemigland (HG) and WG stereotactic body radiotherapy (SBRT) plans.

Methods:

Volumetric-modulated arc radiotherapy-based SBRT plans were designed to treat the left HG, right HG and WG in eight patients, using five fractions of 8 Gy. OARs of interest included the contralateral HG, rectum, urinary bladder, urethra, penile bulb and contralateral neurovascular bundle.

Results:

Rectal V_80% (the percentage of a normal structure receiving a dose of 80%) and V_90% were significantly lower with HG plans than with WG plans (median values of 4.4 vs 2.5 cm³ and 2.1 vs 1.1 cm³, respectively, p < 0.05 by Student''s t-test). Bladder V_50% was also reduced significantly in HG plans (32.3 vs 17.4 cm³, p < 0.05), with a trend towards reduction of V_100% (3.4 vs 1.3 cm³, p = 0.09). Urethral maximum dose and mean doses to the penile bulb and contralateral neurovascular bundle were also reduced significantly (42.0 vs 39.7 Gy, p < 0.00001; 13.3 vs 9.2 Gy, p < 0.05; and 40.2 vs 19.3 Gy, p < 0.00001, respectively).

Conclusion:

Targeting an HG volume rather than a WG volume when delivering SBRT can offer statistically significant reductions for all OARs. Given the large magnitude of the reduction in dose to these OARs, it is anticipated that HG SBRT could offer a superior toxicity profile when compared with WG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.

Advances in knowledge:

The dosimetric feasibility of HG SBRT is demonstrated. When compared with WG SBRT plans, the HG plans demonstrate statistically significant and large magnitude reduction in doses to the rectum, bladder, urethra, penile bulb and contralateral neurovascular bundle, suggesting the possibility of improved toxicity outcomes with HG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.     

Optimizing the flattening filter free beam selection in RapidArc?-based stereotactic body radiotherapy for Stage I lung cancer

Objective:

To optimize the flattening filter-free (FFF) beam selection in stereotactic body radiotherapy (SBRT) treatment for Stage I lung cancer in different fraction schemes.

Methods:

Treatment plans from 12 patients suffering from Stage I lung cancer were designed using the 6XFFF and 10XFFF beams in different fraction schemes of 4 × 12, 3 × 18 and 1 × 34 Gy. Plans were evaluated mainly in terms of organs at risk (OARs) sparing, normal tissue complication probability (NTCP) estimation and treatment efficiency.

Results:

Compared with the 10XFFF beam, 6XFFF beam showed statistically significant lower dose to all the OARs investigated. The percentage of NTCP reduction for both lung and chest wall was about 10% in the fraction schemes of 4 × 12 and 3 × 18 Gy, whereas only 7.4% and 2.6% was obtained in the 1 × 34 Gy scheme. For oesophagus, heart and spinal cord, the reduction was greater with the 6XFFF beam, but their absolute estimates were <10⁻⁶%. The mean beam-on time for 6XFFF and 10XFFF beams at 4 × 12, 3 × 18 and 1 × 34 Gy schemes were 2.2 ± 0.2 vs 1.5 ± 0.1, 3.3 ± 0.9 vs 2.0 ± 0.5 and 6.3 ± 0.9 vs 3.5 ± 0.4 min, respectively.

Conclusion:

The 6XFFF beam obtains better OARs sparing and lower incidence of NTCP in SBRT treatment of Stage I lung cancer, whereas the 10XFFF beam improves the treatment efficiency. To balance the OARs sparing and intrafractional variation owing to the prolonged treatment time, the authors recommend using the 6XFFF beam in the 4 × 12 and 3 × 18 Gy schemes but the 10XFFF beam in the 1 × 34 Gy scheme.

Advances in knowledge:

This study optimizes the FFF beam selection in different fraction schemes in SBRT treatment of Stage I lung cancer.     

Tree-based exploration of the optimization objectives for automatic cervical cancer IMRT treatment planning

Objective:To develop and evaluate a practical automatic treatment planning method for intensity-modulated radiation therapy (IMRT) in cervical cancer cases.Methods:A novel algorithm named as Optimization Objectives Tree Search Algorithm (OOTSA) was proposed to emulate the planning optimization process and achieve a progressively improving IMRT plan, based on the Eclipse Scripting Application Programming Interface (ESAPI). 30 previously treated cervical cancer cases were selected from the clinical database and comparison was made between the OOTSA-generated plans and clinical treated plans and RapidPlan-based (RP) plans.Results:In clinical evaluation, compared with plan scores of the clinical plans and the RP plans, 22 and 26 of the OOTSA plans were considered as clinically improved in terms of plan quality, respectively. The average conformity index (CI) for the PTV in the OOTSA plans was 0.86 ± 0.01 (mean ± 1 standard deviation), better than those in the RP plans (0.83 ± 0.02) and the clinical plans (0.71 ± 0.11). Compared with the clinical plans, the mean doses of femoral head, rectum, spinal cord and right kidney in the OOTSA plans were reduced by 2.34 ± 2.87 Gy, 1.67 ± 2.10 Gy, 4.12 ± 6.44 Gy and 1.15 ± 2.67 Gy. Compared with the RP plans, the mean doses of femoral head, spinal cord, right kidney and small intestine in the OOTSA plans were reduced by 3.31 ± 1.55 Gy, 4.25 ± 3.69 Gy, 1.54 ± 2.23 Gy and 3.33 ± 1.91 Gy, respectively. In the OOTSA plans, the mean dose of bladder was slightly increased, with 2.33 ± 2.55 Gy (versus clinical plans) and 1.37 ± 1.74 Gy (vs RP plans). The average elapsed time of OOTSA and clinical planning were 59.2 ± 3.47 min and 76.53 ± 5.19 min.Conclusion:The plans created by OOTSA have been shown marginally better than the manual plans, especially in preserving OARs. In addition, the time of automatic treatment planning has shown a reduction compared to a manual planning process, and the variation of plan quality was greatly reduced. Although improvement on the algorithm is warranted, this proof-of-concept study has demonstrated that the proposed approach can be a practical solution for automatic planning.Advances in knowledge:The proposed method is novel in the emulation strategy of the physicists’ iterative operation during the planning process. Based on the existing optimizers, this method can be a simple yet effective solution for automated IMRT treatment planning.     

Effect on therapeutic ratio of planning a boosted radiotherapy dose to the dominant intraprostatic tumour lesion within the prostate based on multifunctional MR parameters

Objective:

To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose.

Methods:

The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T₂ maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose–volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan.

Results:

Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p < 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p < 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p < 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p < 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans.

Conclusion:

Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found.

Advances in knowledge:

The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.Phase III trials using conformal external beam radiotherapy have shown that a dose escalation improves biochemical progression-free survival in patients with prostate cancer;^1–5 however, increases in late rectal and urinary morbidity are associated with the dose distributions used to achieve these gains.With the advent of intensity-modulated radiotherapy (IMRT), complex three-dimensional (3D) dose distributions can be delivered to areas of disease whilst reducing the dose to the surrounding tissues and also potentially boosting the dose to encompassed small volumes such as the dominant intraprostatic lesions (DILs). This is potentially advantageous, as local recurrence has been shown to originate within the initial tumour volume.⁶This approach requires reliable and reproducible imaging to identify the DIL. Conventional MR using high spatial resolution T₂ weighted (T2W) contrast has insufficient sensitivity and specificity for defining the tumour within the prostate gland, especially if the lesions are <1 cm in diameter.⁷ A combination of MRI methods whose contrast is determined by tissue physiology and biochemistry rather than anatomy offers improved sensitivity and specificity for delineation of prostate cancers. Functional methods include diffusion-weighted imaging, MR spectroscopic imaging (MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) and together present a multiparametric MRI (mpMRI) data set. We have previously validated a multiparametric model to identify prostate cancer and the location of DILs with histology from prostatectomy specimens.⁸mpMRI data are reliable only if acquired before androgen deprivation (hormone) therapy, as there is profound functional signal degradation after hormone therapy.^9–11 Our standard institutional practice for intermediate- and high-risk localized prostate cancer uses hormone therapy for 3–6 months prior to external beam radiotherapy,^12–14 so modelling a radiation boost to mpMRI-defined tumour nodules requires acquisition of functional data before hormone therapy to be registered with anatomical images obtained post hormone treatment and immediately prior to radiotherapy¹⁵ in order to translate the tumour location to radiotherapy planning CT images. The aim of this planning study therefore was to demonstrate the use of a mpMRI-defined DIL to create a radiotherapy boost volume. IMRT treatment plans were optimized to deliver either a uniform 74 Gy to the whole prostate or to add an 8-Gy simultaneous integrated boost to the DIL, and the potential clinical outcomes compared using dose–volume histograms (DVHs) and radiobiological models for tumour control probability (TCP) and normal tissue complication probabilities (NTCPs).     

Rectal spacer hydrogel in 1.5T MR-guided and daily adapted SBRT for prostate cancer: dosimetric analysis and preliminary patient-reported outcomes

Objective:The main aim of the current analysis was to explore the hypothetical advantages using rectal spacer during 1.5T MR-guided and daily adapted prostate cancer stereotactic body radiotherapy (SBRT) compared to a no-rectal spacer hydrogel cohort of patients.Methods:The SBRT-protocol consisted of a 35 Gy schedule delivered in 5 fractions. Herein, we present a dosimetric analysis between spacer and no-spacer patients. Furthermore, treatment tolerability and feasibility were preliminarily assessed according to clinicians-reported outcomes at the end of treatment and patient-reported outcomes measures (PROMs) in both arms. Toxicity and quality of life were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v. 5.0, International Prostatic Symptoms Score, ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires.Results:120 plans (pre- and daily adaptive SBRT planning) were analyzed in 20 patients (10 patients in spacer group and 10 patients in no-spacer group) treated using 1.5T MR-guided adaptive SBRT. Statistically significant dosimetric advantages were observed in favor of the spacer insertion, improving the planning target volume coverage in terms of V33.2Gy >95% and planning target volume 37.5 Gy <2% mainly during daily-adapted SBRT. Also, rectum V32, V28 and V18Gy and bladder V35Gy <1 cc were significantly reduced in the spacer cohort. Concerning the PROMS, all questionnaires showed no difference between the pre- and post-SBRT evaluation in both arms, excepting the physical functioning item of EORTC QLQ-C30 questionnaire that was declined in the no-spacer group.Conclusion:These preliminary results strongly suggest the adoption of perirectal spacer due to dosimetric advantages not only for rectal sparing but also for target coverage. Longer follow-up is required to validate the clinical impact in terms of clinicians-reported toxicity and PROMs.Advances in knowledge:This the first experience reporting preliminary data concerning the potential dosimetric impact of rectal hydrogel spacer on MR-guided SBRT for prostate cancer.     

Dosimetric feasibility of neurovascular bundle-sparing stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer to preserve erectile function

Objective:We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy.Methods:Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) <60%, V32Gy <70%, V28Gy <90%.Results:Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (p < 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (p < 0.01) and 25% with spacer (p < 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints.Conclusions:NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation.Advances in knowledge:This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.     

Reliability of respiratory-triggered two-dimensional cine k-adaptive-t-autocalibrating reconstruction for Cartesian sampling for the assessment of biventricular volume and function in patients with repaired tetralogy of Fallot

Objective:To compare left ventricular (LV) and right ventricular (RV) volume, function, and image quality of a respiratory-triggered two-dimensional (2D)-cine k-adaptive-t-autocalibrating reconstruction for Cartesian sampling (2D kat-ARC) with those of the standard reference, namely, breath-hold 2D balanced steady-state free precession (2D SSFP), in patients with repaired tetralogy of Fallot (TOF).Methods:30 patients (14 males, mean age 32.2 ± 13.9 years) underwent cardiac magnetic resonance, and 2D kat-ARC and 2D SSFP images were acquired on short-axis view. Biventricular end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and LV mass (LVM) were analysed.Results:The 2D kat-ARC had significantly shorter scan time (35.2 ± 9.1 s vs 80.4 ± 16.7 s; p < 0.0001). Despite an analysis of image quality showed significant impairment using 2D kat-ARC compared to 2D SSFP cine (p < 0.0001), the two sequences demonstrated no significant difference in terms of biventricular EDV, LVESV, LVSV, LVEF, and LVM. However, the RVESV was overestimated for 2D kat-ARC compared with that for 2D SSFP (73.8 ± 43.2 ml vs 70.3 ± 44.5 ml, p = 0.0002) and the RVSV and RVEF were underestimated (RVSV = 46.2±20.5 ml vs 49.4 ± 20.4 ml, p = 0.0024; RVEF = 40.2±12.7% vs. 43.5±14.0%, p = 0.0002).Conclusion:Respiratory-triggered 2D kat-ARC cine is a reliable technique that could be used in the evaluation of LV volumes and function.Advances in knowledge:2D cine kat-ARC is a reliable technique for the assessment LV volume and function in patients with repaired TOF.     

Intensity-modulated radiotherapy increases dose to the brachial plexus compared with conventional radiotherapy for head and neck cancer

Objective

The preferential use of intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in the treatment of head and neck cancer has raised concerns regarding dose to non-target tissue. The purpose of this study was to compare dose-volume characteristics with the brachial plexus between treatment plans generated by IMRT and CRT using several common treatment scenarios.

Method

The brachial plexus was delineated on radiation treatment planning CT scans from 10 patients undergoing IMRT for locally advanced head and neck cancer using a Radiation Therapy Oncology Group-endorsed atlas. No brachial plexus constraint was used. For each patient, a conventional three-g0ield shrinking-g0ield plan was generated and the dose-volume histogram (DVH) for the brachial plexus was compared with that of the IMRT plan.

Results

The mean irradiated volumes of the brachial plexus using the IMRT vs the CRT plan, respectively, were as follows: V50 (18±5 ml) vs (11±6 ml), p = 0.01; V60 (6±4 ml) vs (3±3 ml), p = 0.02; V66 (3±1 ml) vs (1±1 ml), p = 0.04, V70 (0±1 ml) vs (0±1 ml), p = 0.68. The maximum point dose to the brachial plexus was 68.9 Gy (range 62.3–78.7 Gy) and 66.1 Gy (range 60.2–75.6 Gy) for the IMRT and CRT plans, respectively (p = 0.01).

Conclusion

Dose to the brachial plexus is significantly increased among patients undergoing IMRT compared with CRT for head and neck cancer. Preliminary studies on brachial plexus-sparing IMRT are in progress.Although intensity-modulated radiotherapy (IMRT) is widely considered the current standard in the radiotherapeutic management of head and neck cancer, investigators are increasingly recognising that this technology is associated with significant beam path doses to non-target structures that previously received little dose using previous, less conformal techniques [1]. Indeed, since the clinical implementation of IMRT at our institution, we have observed a striking number of patients returning for follow-up with symptoms thought to be related to radiation-induced brachial plexopathy. The purpose of this study was to compare dose-volume characteristics to the brachial plexus between treatment plans generated by IMRT and conventional radiotherapy (CRT) using several common head and neck cancer treatment scenarios.     

Gender is a determinant of carotid artery stiffness independent of age and blood pressure

Objective:To identify the gender-specific differences in carotid artery structural and stiffening parameters by radiofrequency ultrasound (RFU) with an automatic arterial stiffness analyzing system.Methods:Seventy-two consecutive individuals (32 males and 40 females, age range from 36 to 62 years) with no history of significant cardiovascular diseases or carotid artery plaques were enrolled between September and December 2017. Quality intima-media thickness (QIMT) and quality arterial stiffness (QAS) parameters were automatically computed, including pulse wave velocity (PWV), vascular distension, compliance coefficient (CC), distensibility coefficient (DC), stiffness index α and β, augmentation pressure (AP), and augmentation index (AIx). Those parameters were compared between males and females. Multiple linear regression analysis was performed to assess the independent association between gender and RFU parameters.Results:The mean age had no difference between males and females (47.8 ± 3.3 vs 50.0 ± 8.5 years, p = 0.19). Females had higher systolic blood pressure (134.53 ± 9.65 vs 127.78 ± 6.12 mm Hg) and diastolic blood pressure (85.83 ± 3.94 vs 78.03 ± 5.22 mm Hg), greater carotid QIMT (598.73 ± 72.16 vs 550.84 ± 29.37 µm), advanced PWV (8.08 ± 1.60 vs 6.24 ± 0.70 m/s), higher stiffness index α (6.21 ± 1.94 vs 3.95 ± 0.78) and β (9.43 ± 3.17 vs 6.38 ± 0.78), higher AP (6.68 ± 2.24 vs 3.64 ± 1.22 mm Hg) and AIx (7.42 ± 2.08 vs 4.69 ± 1.26%), all p < 0.001. Multiple linear regression analysis demonstrated gender was independently associated with carotid structural and elastic parameters.Conclusion:Gender independently impacts carotid structure and function, with females more vulnerable to the progression of arterial aging. Awareness of the gender differences on the risk stratification of carotid artery disease will benefit reliable assessments and specific management recommendations in clinical practice.Advances in knowledge:(1) RFU provides an μm-unit quality IMT measurement and multiple quality arterial stiffness parameters. (2) Gender is an independent determinant in both the arterial structural and elastic aspects, with females of stiffer arteries in low CVD risk individuals.     

Stent evaluation by coronary computed tomography angiography: a comparison between Iopamidol-370 and Ioversol-320 hypo-osmolar iodine concentration contrasts

Objective:Qualitative and quantitative image analysis between Iopamidol-370 and Ioversol-320 in stents´ evaluation by coronary computed tomography angiography (CTA).Methods:Sixty-five patients with low-risk stable angina undergoing stent follow-up with coronary CTA were assigned to Iopamidol I-370 (n = 33) or Ioversol I-320 (n = 32) in this prospective, double-blind, non-inferiority, randomized trial. Stent lumen image quality was graded by 5-point Likert Scale. Lumen mean attenuation was measured at native coronary segments: pre-stent, post-stent, distal segments and at coronary plaques. Lumen attenuation increase (LAI) ratio was calculated for all stents. Heart rate (HR) variation, premature heart beats (PHB), heat sensation (HS), blooming and beam hardening were also assessed.Results:Image quality was similar between groups, with no significant difference (Likert score 4.48 ± 0.75 vs 4.54 ± 0.65, p = 0.5). There were similarities in LAI ratio between I-370 and I-320 (0.39 ± 0.42 vs 0.48 ± 0.44 HU, p = 0.08). Regarding lumen mean attenuation at native coronary segments, a significant difference was observed, with I-320 presenting lower values, including contrast mean attenuation in distal segments. After statistical multivariate analysis, three variables correlated with stent image quality: 1) stent diameter, 2) HR variation and 3) stent lumen LAI ratio.Conclusions:There was no significant difference between Iopamidol-370 mgI ml⁻¹ and Ioversol-320 mgI ml⁻¹ contrasts regarding overall stent lumen image quality, which was mainly influenced by stent diameter, HR and LAI ratio. Advances in knowledge: Coronary CTA allows adequate stents'' visualization and image quality is influenced by stent diameter, HR variation and LAI ratio.Stents'' image quality showed no difference between different concentration contrasts (I-370 vs. I-320); however, higher concentration contrasts may provide an improved overall visualization, especially regarding coronary distal segments.     

Left anterior descending artery avoidance in patients receiving breast irradiation

PurposeDose to the left anterior descending artery (LAD) may be significant in patients receiving left-sided irradiation for breast cancer. We investigated if prospective contouring and avoidance of the LAD during treatment planning were associated with lower LAD dose.Methods and MaterialsWe reviewed dosimetric plans for 323 patients who received left whole breast or chest wall irradiation with or without internal mammary node (IMLN) coverage between 1/2014 and 1/2019 at a single institution. The LAD was contoured prospectively for 155 cases, and techniques were utilized to minimize LAD dose. Dose-volume-histograms from these patients were compared to those of 168 patients for whom the LAD was contoured retrospectively after treatment completion. EQD2 was calculated to account for fractionation differences.ResultsCompared to cases where the LAD was contoured retrospectively (n = 126), prospective LAD contouring (n = 124) was associated with lower unadjusted median max and mean LAD doses for 250 patients receiving whole-breast irradiation (WBI) without IMLN coverage: 8.5 Gy vs 5.2 Gy (p < 0.0001) and 3.6 Gy vs 2.7 Gy (p < 0.0001), respectively. EQD2 median max and mean LAD doses were also lower with prospective LAD contouring: 5.2 Gy vs 3.0 Gy (p < 0.0001) and 1.9 Gy vs 1.5 Gy (p < 0.0001), respectively. Compared to cases where the LAD was contoured retrospectively (n = 42), prospective LAD contouring (n = 31) was associated with lower max LAD doses for 73 patients with IMLN coverage: 20.4 Gy vs 14.3 Gy (p = 0.042). There was a nonsignificant reduction in median mean LAD dose: 6.2 Gy vs 6.1 Gy (p = 0.33). LAD doses were reduced while maintaining IMLN coverage (mean V90%_Rx >90%).ConclusionsProspective contouring and avoidance of the LAD were associated with lower max and mean LAD doses in patients receiving WBI and with lower max LAD doses in patients receiving IMLN treatment. Further reduction in LAD dose may require stricter optimization weighting or compromise in IMLN coverage.     

CT-guided preoperative localization of ground glass nodule: comparison between the application of embolization microcoil and the locating needle designed for pulmonary nodules

Objectives:To compare the efficacy and safety of pre-operative localization of ground glass nodule (GGN) using embolization microcoils and the locating needles designed for pulmonary nodules.Methods:From June 2019 to December 2020, 429 patients who received CT-guided localization of single GGN before video-assisted thoracoscopic surgery (VATS) were enrolled. The diameter and depth of GGNs were 0.84 ± 0.39 cm and 1.66 ± 1.37 cm. Among 429 cases, the first 221 GGNs were marked with microcoils (the microcoil group), and the remaining 208 GGNs were marked with the locating needles designed for pulmonary nodules (the locating needle group). SPSS 17.0 statistical software was used to compare the marking success rate, marking time, marking-related complications between two groups. p values < 0.05 were considered statistically significant.Results:The marking time in the microcoil group was longer than that in the locating needle group (11.1 ± 3.9 vs 8.2 ± 2.0 min, t = −7.87, p = 0.000). The marking success rate in the microcoil group was lower than that in the locating needle group (91.4% vs 98.6%, χ² = 11.27, p = 0.001). In the microcoil group, marking failures included 16 cases of microcoil dislocation and 3 cases of unsatisfactory microcoil position, while all 3 cases of marking failure in the locating needle group were due to unsatisfactory anchor position. No significant differences in the incidence of total complications (23.1% vs 22.1%), pneumothorax (18.1% vs 19.2%), hemorrhage (9.5% vs 9.1%), and hemoptysis (1.8% vs 1.4%) were observed between the two groups. All the complications were minor and did not need special treatment. Except for one case in the microcoil group, which was converted to thoracotomy, the remaining 428 GGNs were successfully resected by VATS.Conclusions:It is safe and effective to perform pre-operative localization of GGN using either embolization microcoil or the locating needle designed for pulmonary nodules. The locating needle is superior to microcoil for marking GGN in terms of procedure time and the success rate. The complication rate of both methods is similar.Advances in knowledge:The locating needle designed for pulmonary nodules has recently been used to mark pulmonary nodule. Its structure can effectively avoid dislocation after localization, and the marking process is simple and quick. Compared with localization using microcoil, it takes less time and has higher success rate to mark GGNs using the locating needle. The complication rate of both methods is similar.     

Safely achieving single prolonged breath-holds of > 5 minutes for radiotherapy in the prone,front crawl position

Objective:Breast cancer radiotherapy is increasingly delivered supine with multiple, short breath-holds. There may be heart and lung sparing advantages for locoregional breast cancer of both prone treatment and in a single breath-hold. We test here whether single prolonged breath-holds are possible in the prone, front crawl position.Methods:19 healthy volunteers were trained to deliver supine, single prolonged breath-holds with pre-oxygenation and hypocapnia. We tested whether all could achieve the same durations in the prone, front crawl position.Results:19 healthy volunteers achieved supine, single prolonged breath-holds for mean of 6.2 ± 0.3 min. All were able to hold safely for the same duration while prone (6.1 ± 0.2 min ns. by paired ANOVA). With prone, the increased weight on the chest did not impede chest inflation, nor the ability to hold air in the chest. Thus, the rate of chest deflation (mean anteroposterior deflation movement of three craniocaudally arranged surface markers on the spinal cord) was the same (1.2 ± 0.2, 2.0 ± 0.4 and 1.2 ± 0.4 mm/min) as found previously during supine prolonged breath-holds. No leakage of carbon dioxide or air was detectable into the facemask.Conclusion:Single prolonged (>5 min) breath-holds are equally possible in the prone, front crawl position.Advances in knowledge:Prolonged breath-holds in the front crawl position are possible and have the same durations as in the supine position. Such training would therefore be feasible for some patients with breast cancer requiring loco-regional irradiation. It would have obvious advantages for hypofractionation.     

Postmastectomy Radiotherapy of the Chest Wall

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for postmastectomy irradiation. A retrospective analysis of patterns of locoregional failure (LRF) after modified radical mastectomy and axillary lymph node dissection followed by locoregional radiotherapy with or without systemic treatment was performed. Main emphasis was focused on the comparison of two postmastectomy radiotherapy techniques. PATIENTS AND METHODS: 287 evaluable patients with locally advanced disease and/or adverse pathologic features (pT3 17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%) with or without adjuvant chemo-hormonal treatment were included between 1989 and 2000. Median age was 61 years (range 24-88 years). All patients had modified radical mastectomy and axillary lymphonodectomy level I-II(III) for primary breast cancer. Median total dose of conventionally fractionated radiotherapy to the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10 Gy was applied in 72 patients. 80% of the patients received supraclavicular and 60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27% chemotherapy. The median follow-up of patients at risk was 43 months (average 54 months). RESULTS: The 5-year locoregional tumor control (LRC), LRC first event, disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier analysis), respectively. Cox regression analysis showed that stage III (relative risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional failure, while positive estrogen receptor status (RR 0.3) was associated with a reduced risk. No statistically significant differences in LRC were observed for patients treated either with the electron-rotation technique (LRC 92%) or with the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors resected with "close margins" showed a higher LRF rate of 25% after electronbeam-rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed 6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm developed LRF in 29% of patients treated with electron-beam-rotation irradiation and in 17% of patients with photon-based irradiation (p = 0.1). CONCLUSION: In locally advanced breast cancer, the LRC after postmastectomy irradiation with both techniques is comparable with published data from randomized studies. The tangential opposed photon field technique seems to be beneficial after marginal resection (histopathologic "close margins") of the primary tumor.     

Sexual organ-sparing with hydrogel spacer injections for rectal cancer radiotherapy: a feasibility pilot study

Objectives:The aim of this pilot study was to investigate in two rectal cancer patients undergoing neoadjuvant chemo-radiotherapy (nCRT) the implant feasibility and dosimetric benefit in sexual organ-sparing of an injectable, absorbable, radiopaque hydrogel spacer.Methods:Two rectal cancer patients (one male and one female) underwent hydrogel implant between rectum and vagina/prostate before nCRT and curative surgery. A CT scan was performed before and after injection and a comparative dosimetric study was performed testing a standard (45/50 Gy) and a dose escalated (46/55.2 Gy) schedule.Results:In both patients, the spacer implant in the recto-prostatic or recto-vaginal space was feasible and well tolerated. For the male, the dosimetric benefit with spacer was minimal for sexual organs. For the female however, doses delivered to the vagina were significantly reduced with spacer with a mean reduction of more than 5 Gy for both regimens.Conclusions:For organ preservation protocols and selected sexually active female patients, use of hydrogel spacers can be considered to spare sexual organs from the high radiotherapy dose levels.Advances in knowledge:For females with advanced rectal tumor, a spacer implant between the rectum and the vagina before nCRT is feasible and reduces doses delivered to the vagina.     

Reducing contrast medium dose with low photon energy images in renal dual-energy spectral CT angiography and adaptive statistical iterative reconstruction (ASIR)

Objective:To evaluate the value of using low energy (keV) images in renal dual-energy spectral CT angiography (CTA) and adaptive statistical iterative reconstruction (ASIR) to reduce contrast medium dose.Methods:40 patients with renal CTA on a Discovery CT750HD were randomly divided into two groups: 20 cases (Group A) with 600 mgI kg⁻¹ and 20 cases (Group B) with 300 mgI kg⁻¹. The scan protocol for both groups was: dual-energy mode with mA selection for noise index of 10 HU, pitch 1.375:1, rotating speed 0.6 s/r. Images were reconstructed at 0.625 mm thickness with 40%ASIR, Group A used the conventional 70keV monochromatic images, and Group B used monochromatic images from 40 to 70 keV at 5 keV interval for analysis. The CT values and standard deviation (SD) values of the renal artery and erector spine in the plain and arterial phases were measured with the erector spine SD value representing image noise. The enhancement degree of the renal artery (ΔCT = CT(arterial) -CT(plain)), signal-to-noise ratio (SNR=CT_renal-artery/SD_renal-artery) and contrast-to-noise ratio (CNR=(CT_renal-artery-CT_{erector spine})/SD_{erector-spine}) were calculated. The single factor analysis of variance was used to analyze the difference of ΔCT, SNR and CNR among image groups with p < 0.05 being statistically significant. The subjective image scores of the groups were assessed blindly by two experienced physicians using a 5-point system and the score consistency was compared by the κ test.Results:Contrast medium dose in the 300 mgI kg⁻¹ group was reduced by 50% compared with the 600 mgI kg⁻¹ group, while radiation dose was similar between the two groups. The subjective scores were 4.00 ± 0.65, 4.50 ± 0.60 and 3.70 ± 0.80 for images at 70 keV (600 mgI kg⁻¹ group), 40 keV (300 mgI kg⁻¹ group) and 45 keV (300 mgI kg⁻¹ group), respectively with good consistency between the two reviewers (p > 0.05). The 40 keV images in the 300 mgI kg⁻¹ group had similar ΔCT (469.77 ± 86.95 HU vs 398.54 ± 73.68 HU) and CNR (15.52 ± 3.32 vs 18.78 ± 6.71) values as the 70 keV images in the 600 mgI kg⁻¹) group but higher SNR values (30.19 ± 4.41 vs 16.91 ± 11.12, p < 0,05)Conclusion:Contrast dose may be reduced by 50% while maintaining image quality by using lower energy images combined with ASIR in renal dual-energy CTA.Advances in knowledge:Combined with ASIR and energy spectrum, can reduce the amount of contrast dose in renal CTA.     

Intensity-modulated extended-field chemoradiation plus simultaneous integrated boost in the pre-operative treatment of locally advanced cervical cancer: a dose-escalation study

Objective:

To investigate the feasibility and determine the recommended pre-operative intensity-modulated radiotherapy (IMRT) dose of extended-field chemoradiation along with simultaneous integrated boost (SIB) dose escalation.

Methods:

A radiation dose of 40 Gy over 4 weeks, 2 Gy/fraction, was delivered to the tumour and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: Level 1 (PTV3: 40/2 Gy; PTV2: 40/2 Gy; PTV1: 45/2.25 Gy), Level 2 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 45/2.25 Gy) and Level 3 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 50/2.5 Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if two of the six patients in a cohort experienced dose-limiting toxicity within 3 months from treatment.

Results:

19 patients [median age: 46 years; The International Federation of Gynecology and Obstetrics (FIGO) stage IB2: 3, IIB: 10, IIIA–IIIB: 6] were enrolled. Median follow-up was 24 months (9–60 months). The most common grade 3/4 toxicity was gastrointestinal (GI) (diarrhoea, mucous discharge, rectal/abdominal pain). At Levels 1 and 2, only one grade 3 GI toxicity per level was recorded, whereas at Level 3, two grade 3 GI toxicities (diarrhoea, emesis and nausea) were recorded.

Conclusion:

The SIB-IMRT technique was found to be feasible and safe at the recommended doses of 45 Gy to PTV1 and PTV2 and 40 Gy to PTV3 in the pre-operative treatment of patients with locally advanced cervical cancer. Unfortunately, this complex technique was unable to safely escalate dose beyond levels already achieved with three-dimensional conformal radiotherapy technique given acute GI toxicity.

Advances in knowledge:

A Phase I radiotherapy dose-escalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.