Comparison of clinical, tumour-related and dosimetric factors in grade 0-1, grade 2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours

Objective

The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0–1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours.

Methods

Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose–volume histograms (DVHs) were constructed to identify the incidence of RP.

Results

The median follow-up period was 12 months (range, 6–45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5–30 Gy (V5–30) and mean lung dose were significant factors differentiating between grade 0–1 and grade 2 RP, and V15–30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0–1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0–1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0–2 RP.

Conclusions

Grade 0–2 RP was dose–volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0–2 RP. However, incidences of V15–30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.Previously, we investigated the clinical and dosimetric factors that correlate with severe radiation pneumonitis (RP) in patients with lung tumours treated with stereotactic body radiotherapy (SBRT) [1]. We found that, among a variety of factors, only a short latent period was a significant correlate of severe RP.Other reports [2-6] have also analysed the clinical and dosimetric factors correlated with RP after SBRT. Various dosimetric factors were reported to significantly correlate with RP after SBRT, which included the mean dose in the ipsilateral lung, V7 and V10 by Kyas et al [2], normal tissue complication probability (NTCP) by Ricardi et al [3], lung volumes treated with doses higher than 2.5–50 Gy (V2.5–50) by Guckenberger et al [4], mean lung dose by Barriger et al [5] and contralateral V5 by Ong et al [6].We found a discrepancy in the significant clinical and dosimetric factors between the results of these five studies on low-grade RP [2-6] and our study on severe RP [1]. We speculated that the mechanism underlying the development of grade ≥3 RP might be different from that of grade 2 RP. Additionally, the treatment of grade ≥3 RP was much more critical than that of grade 2 RP. Most patients with grade ≥3 RP needed to be admitted to hospital and steroids or oxygen therapy were administered. By contrast, patients with grade 2 RP were simply followed up carefully without administration of medication as outpatients.In the present study, to ascertain this discrepancy, we analysed the clinical and dosimetric factors that correlated with RP after SBRT among patients with grade 0–1, grade 2 and grade 3 RP in the same sample of patients as that included in our previous study [1].     

Prognostic factors associated with a subchondral insufficiency fracture of the femoral head

Objective

The aim of this study was to identify the risk factors associated with the prognosis of a subchondral insufficiency fracture of the femoral head (SIF).

Methods

Between June 2002 and July 2009, 25 patients diagnosed with SIF were included in this study. Sequential radiographs were evaluated for the progression of collapse. Clinical profiles, including age, body mass index, follow-up period and Singh’s index, were documented. The morphological characteristics of the low-intensity band on T₁ weighted MRI were also examined with regards to four factors: band length, band thickness, the length of the weight-bearing portion and the band length ratio (defined as the proportion of the band length to the weight-bearing portion of the femoral head in the slice through the femoral head centre).

Results

Radiographically, a progression of collapse was observed in 15 of 25 (60.0%) patients. The band length in patients with progression of collapse [22.5 mm; 95% confidence interval (CI) 17.7, 27.3] was significantly larger than in patients without a progression of collapse (13.4 mm; 95% CI 7.6, 19.3; p<0.05). The band length ratio in patients with progression of collapse (59.8%; 95% CI 50.8, 68.9) was also significantly higher than in patients without a progression of collapse (40.9%; 95% CI 29.8, 52.0; p<0.05). No significant differences were present in the other values.

Conclusion

These results indicate that the band length and the band length ratio might be predictive for the progression of collapse in SIF.Subchondral insufficiency fractures of the femoral head (SIF) often occur in osteoporotic elderly patients [1-9]. Patients usually suffer from acute hip pain without any obvious antecedent trauma. Radiologically, a subchondral fracture is seen primarily in the superolateral portion of the femoral head [4,5,10]. T₁ weighted MRI reveal a very low-intensity band in the subchondral area of the femoral head, which tends to be irregular, disconnected and convex to the articular surface [2,4,5,7,9,11]. This low-intensity band in SIF was histologically proven to correspond with the fracture line and associated repair tissue [5,9]. Some cases of SIF resolve after conservative treatment [5,11-14]; other cases progress until collapse, thereby requiring surgical treatment [4-10,15]. The prognosis of SIF patients remains unclear.The current study investigated the risk factors that influence the prognosis of SIF based on the progression to collapse.     

Accessory or additional renal arteries show no relevant effects on the width of the upper urinary tract: a 64-slice multidetector CT study in 1072 patients with 2132 kidneys

Objective

The aim of this study was to find out on an unselected patient group whether crossing vessels have an influence on the width of the renal pelvis and what independent predictors of these target variables exist.

Methods

In this cross-sectional study, 1072 patients with arterially contrasted CT scans were included. The 2132 kidneys were supplied by 2736 arteries.

Results

On the right side, there were 293 additional and accessory arteries in 286 patients, and on the left side there were 304 in 271 patients. 154 renal pelves were more than 15 mm wide. The greatest independent factor for hydronephrosis on one side was hydronephrosis on the contralateral side (p<0.0001 each). Independent predictors for the width of the renal pelvis on the right side were the width of the renal pelvis on the left, female gender, increasing age and height; for the left side, predictors were the width of the renal pelvis on the right, concrements, parapelvic cysts and great rotation of the upper pole of the kidney to dorsal. Crossing vessels had no influence on the development of hydronephrosis. Only anterior crossing vessels on the right side are associated with widening of the renal pelvis by 1 mm, without making it possible to identify the vessel as an independent factor in multivariate regression models.

Conclusion

The width of the renal pelvis on the contralateral side is the strongest independent predictor for hydronephrosis and the width of the renal pelvis. There is no link between crossing vessels and the width of the renal pelvis.Obstructions of the ureteropelvic junction (UPJ) can be caused by intrinsic or extrinsic factors [1]. Although there are no studies of this to date, crossing the UPJ by an aberrant crossing vessel is considered the most important [2] of the extrinsic factors [3]. Crossing vessels, which are thought to cause from 40% to over 50% of the extrinsic UPJ obstructions in adults [4, 5], are located ventral more often than dorsal to the UPJ. These are usually normal vessels of the lower pole segment [4, 6–9], which can be divided into additional renal arteries arising from the aorta, and accessoric renal arteries arising from branches of the aorta [10, 11]. The primary surgical therapy of choice is endoscopic endopyelotomy [12]. The success rate of 89–90% [12, 13] is thought to be noticeably poorer in patients with crossing vessels [12, 13]; however, this is not undisputed [14, 15]. Be that as it may, to prevent bleeding complications it is necessary to be familiar with the vascular situation around the UPJ prior to the procedure [3, 16–18]. CT angiography is used for this purpose, as it is highly accurate, quick to perform and shows all relevant anatomical structures in relation to one another [3, 19, 20]. The objective of this study was to determine whether or not there are vascular morphological patterns or other factors that influence the width of the renal collecting system, regardless of the definitions of hydronephrosis.     

Pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy

Objective:

To describe the pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy (IMRT) for oropharyngeal cancer.

Methods:

A cohort of patients undergoing weekly CT scans during dose-painted IMRT was considered. The parotid glands were contoured at the time of treatment planning (baseline) and on all subsequent scans. For a given patient, the parotid glands were labelled as higher (H) and lower (L), based on the mean dose at planning. The volume of each gland was determined for each scan and the percent change from baseline computed. Data were fit to both linear and quadratic functions. The role of selected covariates was assessed with both logistic regression and pair-wise comparison between the sides. The analyses were performed considering the whole treatment duration or each separate half.

Results:

85 patients, 170 glands and 565 scans were analysed. For all parotids except one, the quadratic function provided a better fit than the linear one. Moreover, according to both the logistic regression and pair-wise comparison, the cumulative mean dose of radiation is independently correlated with the parotid shrinkage during the first but not the second half of the treatment. Conversely, age and weight loss are predictors of relative parotid shrinkage during the entire course of the treatment.

Conclusion:

Parotid gland shrinkage during IMRT is not linear. Age, weight loss and radiation dose independently predict parotid shrinkage during a course of IMRT.

Advances in knowledge:

The present study adds to the pathophysiology of parotid shrinkage during radiotherapy.Fractionated radiotherapy is based on the assumption that the dose distribution obtained at planning is delivered during each treatment session. However, both set-up errors and tissue deformation can modify the dose that is administered. Shifts in the location of isodose levels compared with planning become critical for techniques that are highly conformal to the target(s), such as IMRT, justifying the interest in image guidance and adaptive radiotherapy [1]. Because of the sharp dose gradient around the target(s), subtle changes in the relative position or in the volume of organs at risk may alter the planned dose that the volume of an organ receives, as has been shown for the parotid glands [2–6].In a study by Ricchetti et al [7], we found that the parotid glands are the regions of interest that undergo the largest absolute and relative changes in volume during treatments. Although at least 16 articles have documented a significant percent reduction in the volume of the parotid gland during the course of fractionated radiotherapy [2,3,7–20], there are still several unanswered questions. It is unclear why some parotid glands shrink to about 50–60% during treatment, while others show only minimal changes. Studies that have investigated predictors of shrinkage have suggested weight loss during treatment, patient age and dose of radiation to the parotid as potential factors [2,9,16–19]. However, results are inconsistent [3,8,10,14]. Some studies have suggested that dosimetrically spared parotid glands undergo only minimal volume changes during treatment [16,18], whereas others describe a similar behaviour regardless of the radiation dose [7,8,10]. Furthermore, it is unclear whether the daily percent volume change is constant [8,10,16,19] or variable [7,10,13] during the course of treatment. A variable daily percent change in the volume may indicate that there are predictive factors specific to certain portions of the fractionated radiation schedule. In the present article, we attempt to clarify these points.     

Correlation between computerised findings and Newman's scaling on vascularity using power Doppler ultrasonography imaging and its predictive value in patients with plantar fasciitis

Objectives

The purpose of this study was to correlate findings on small vessel vascularity between computerised findings and Newman''s scaling using power Doppler ultrasonography (PDU) imaging and its predictive value in patients with plantar fasciitis.

Methods

PDU was performed on 44 patients (age range 30–66 years; mean age 48 years) with plantar fasciitis and 46 healthy subjects (age range 18–61 years; mean age 36 years). The vascularity was quantified using ultrasound images by a customised software program and graded by Newman''s grading scale. Vascular index (VI) was calculated from the software program as the ratio of the number of colour pixels to the total number of pixels within a standardised selected area of proximal plantar fascia. The 46 healthy subjects were examined on 2 occasions 7–10 days apart, and 18 of them were assessed by 2 examiners. Statistical analyses were performed using intraclass correlation coefficient and linear regression analysis.

Results

Good correlation was found between the averaged VI ratios and Newman''s qualitative scale (ρ = 0.70; p<0.001). Intratester and intertester reliability were 0.89 and 0.61, respectively. Furthermore, higher VI was correlated with less reduction in pain after physiotherapeutic intervention.

Conclusions

The computerised VI not only has a high level of concordance with the Newman grading scale but is also reliable in reflecting the vascularity of proximal plantar fascia, and can predict pain reduction after intervention. This index can be used to characterise the changes in vascularity of patients with plantar fasciitis, and it may also be helpful for evaluating treatment and monitoring the progress after intervention in future studies.Plantar fasciitis is the most common cause of heel pain, and about 2 000 000 patients in the USA receive treatment every year because of this condition [1]. Besides mechanical loading, vascular disturbance with consequent metabolic impairment and hypoxia is thought to play an important role [2]. Indeed, fibrovascular hyperplasia and vascular proliferation were observed from microscopic specimens obtained from operative resection [3-5]. Walther et al [6] were the first group to evaluate plantar fascia vascularity non-invasively using power Doppler ultrasonography (PDU).PDU is one of the colour flow imaging techniques that encodes the amplitude of the power spectral density of the Doppler signals [7]. This method has been used to assess soft-tissue vascularity and treatment efficacy with a variety of musculoskeletal and related problems. Changes in vascularity in synovial tissues in patients with rheumatoid arthritis [8-11], osteoarthritis [12,13], tendinopathy [6,14-21] and plantar fasciitis [6] have been reported. Modulation in vascularity was observed in patients with tendinopathy after a course of intervention [14-21]. Most of these studies used the Newman''s grading scale to grade the tissue vascularity [19-21]. This qualitative grading for the PDU images had high correlation with the histopathological grading of vascularity of the synovial membrane in patients with arthritis [11]. Nevertheless, Newman''s grading system may not be objective and sensitive enough to differentiate subtle vascularity changes.Recently, computerised methods were used to quantify tissue vascularity with ultrasonography. Tissue vascularity was quantified by computing a vascular index (VI), which is calculated as the ratio of the number of colour pixels to the total number of pixels within the region of interest in patients with soft-tissue problems [8,9,11,17]. Note that most of these studies were conducted using colour Doppler ultrasonography. In this connection, PDU is superior to frequency-based colour Doppler ultrasonography, especially in tissues with low blood flow, such as the plantar fascia [6,22,23]. Ying et al [24] reported the feasibility of computerised quantification of vascularity in thyroid tissues with PDU. We were interested in evaluating whether the computerised quantification of vascularity could be applied on musculoskeletal tissue, such as the plantar fascia. Therefore, the purpose of the present study was to correlate the computerised VI and Newman''s qualitative grading scale in quantifying plantar fascia vascularity using PDU, to evaluate the intra- and intertester reliability of the computerised quantitative method and its predictive ability of recovery in patients with plantar fasciitis. Proximal plantar fascia, which is the most commonly affected area in individuals with plantar fasciitis, according to clinical examination [25,26] and previous B-mode ultrasonography [26-28], was chosen as the target testing area.     

Correlation between gamma index passing rate and clinical dosimetric difference for pre-treatment 2D and 3D volumetric modulated arc therapy dosimetric verification

Objective:

To investigate comparatively the percentage gamma passing rate (%GP) of two-dimensional (2D) and three-dimensional (3D) pre-treatment volumetric modulated arc therapy (VMAT) dosimetric verification and their correlation and sensitivity with percentage dosimetric errors (%DE).

Methods:

%GP of 2D and 3D pre-treatment VMAT quality assurance (QA) with different acceptance criteria was obtained by ArcCHECK® (Sun Nuclear Corporation, Melbourne, FL) for 20 patients with nasopharyngeal cancer (NPC) and 20 patients with oesophageal cancer. %DE were calculated from planned dose–volume histogram (DVH) and patients'' predicted DVH calculated by 3DVH® software (Sun Nuclear Corporation). Correlation and sensitivity between %GP and %DE were investigated using Pearson''s correlation coefficient (r) and receiver operating characteristics (ROCs).

Results:

Relatively higher %DE on some DVH-based metrics were observed for both patients with NPC and oesophageal cancer. Except for 2%/2 mm criterion, the average %GPs for all patients undergoing VMAT were acceptable with average rates of 97.11% ± 1.54% and 97.39% ± 1.37% for 2D and 3D 3%/3 mm criteria, respectively. The number of correlations for 3D was higher than that for 2D (21 vs 8). However, the general correlation was still poor for all the analysed metrics (9 out of 26 for 3D 3%/3 mm criterion). The average area under the curve (AUC) of ROCs was 0.66 ± 0.12 and 0.71 ± 0.21 for 2D and 3D evaluations, respectively.

Conclusions:

There is a lack of correlation between %GP and %DE for both 2D and 3D pre-treatment VMAT dosimetric evaluation. DVH-based dose metrics evaluation obtained from 3DVH will provide more useful analysis.

Advances in knowledge:

Correlation and sensitivity of %GP with %DE for VMAT QA were studied for the first time.Volumetric modulated arc therapy (VMAT) is a novel delivery method of intensity-modulated radiotherapy (IMRT). It is capable of delivering highly conformal dose distributions through concomitant continuous gantry rotation, dynamic beam modulation and variable dose rate.^1,2 Owing to its rotational delivery features, VMAT is more complex than conventional IMRT in both planning and dosimetric evaluations.^3,4Quality assurance (QA) for VMAT is relatively new with respect to the established dosimetric verification of fixed-beam IMRT with two-dimensional (2D) arrays. Verifying the whole plan while the gantry is rotating is rather challenging.^5,6 Numerous approaches and phantoms have been investigated for the QA of VMAT, including Monte Carlo simulation,⁷ ScandiDos Delta⁴® (ScandiDos, Uppsala, Sweden),⁸ GAFCHROMIC® EBT (International Specialty Products, Wayne, NJ) films,⁹ MatriXX™ 2D ionization chamber array with a MultiCube™ phantom (IBA Dosimetry Inc., Memphis, TN),¹⁰ 2D-ARRAT seven29 and Octavius phantom (PTW, Freiburg, Germany), electronic portal imaging device and three-dimensional (3D) diode array ArcCHECK® (Sun Nuclear Corporation, Melbourne, FL).⁶Until now, no standardized QA procedure and acceptance criteria specific for VMAT have been established. Those performing VMAT QA are typically using QA methods and action levels taken from fixed-beam IMRT QA methods. Phantom dose verification, gamma index with 3% dose difference and 3-mm dose-to-distance criteria are most commonly used by physicists in pre-treatment IMRT and VMAT QA as reported in the AAPM Task Group 119 and some other articles.^11–13 However, recent studies demonstrated that there is no correlation between the percentage gamma passing rate (%GP) and the magnitude of dose discrepancy between the planned dose and the actual delivered dose for IMRT.^14,15 This also raises concern about whether the %GP is correlated with clinical dosimetric difference for VMAT.The main purpose of this study is to investigate comparatively the %GP of 2D and 3D VMAT dosimetric verification with different acceptance criteria, and their correlation and sensitivity with percentage dosimetric errors (%DE) between planned dose–volume histogram (DVH) and patients'' predicted DVH calculated by 3DVH® software (Sun Nuclear Corporation).     

Iron overload: accuracy of in-phase and out-of-phase MRI as a quick method to evaluate liver iron load in haematological malignancies and chronic liver disease

Objectives

The purpose of this prospective study was to evaluate the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration in patients with haematological malignancies and chronic liver disease.

Methods

MRI-based hepatic iron concentration (M-HIC, μmol g^–1) was used as a reference standard. 42 patients suspected of having iron overload and 12 control subjects underwent 1.5 T in- and out-of-phase and M-HIC liver imaging. Two methods, semi-quantitative visual grading made by two independent readers and quantitative relative signal intensity (rSI) grading from the signal intensity differences of in-phase and out-of-phase images, were used. Statistical analyses were performed using the Spearman and Kruskal–Wallis tests, receiver operator curves and κ coefficients.

Results

The correlations between M-HIC and visual gradings of Reader 1 (r=0.9534, p<0.0001) and Reader 2 (r=0.9456, p<0.0001) were higher than the correlations of the rSI method (r=0.7719, p<0.0001). There was excellent agreement between the readers (weighted κ=0.9619). Both visual grading and rSI were similar in detecting liver iron overload: rSI had 84.85% sensitivity and 100% specificity; visual grading had 85% sensitivity and 100% specificity. The differences between the grades of visual grading were significant (p<0.0001) and the method was able to distinguish different degrees of iron overload at the threshold of 151 μmol g^–1 with 100% positive predictive value and negative predictive value.

Conclusion

Detection and grading of liver iron can be performed reliably with in-phase and out-of-phase imaging. Liver fat is a potential pitfall, which limits the use of rSI.Iron overload is a clinically recognised condition with variety of aetiologies and clinical manifestations [1-4]. Liver iron concentration correlates closely with the total body iron stores [5]. The excess iron accumulates mainly in the liver and the progressive accumulation of toxic iron can lead to organ failure if untreated [2,4]. Several diseases causing iron overload, such as transfusion-dependent anaemia, haematological malignancies, thalassaemia, haemochromatosis and chronic liver disease, result in a large number of patients with a potentially treatable iron overload [1,2,4].Several quantitative MRI methods for iron overload measurement by multiple sequences have been established, such as proportional signal intensity (SI) methods and proton transverse relaxation rates (R₂, R₂*) [4,6,7]. A gradient echo liver-to-muscle SI-based algorithm [8] has been widely validated and used for quantitative liver iron measurement [8-11]. MRI-based hepatic iron concentration (M-HIC, μmol g^–1 liver dry weight) with corresponding R₂* [9] can be calculated with this method which is a directly proportional linear iron indicator, virtually independent of the fat fraction, as the echo times are taken in-phase [8,9]. This method showed a high accuracy in calibrations with the biochemical analysis of liver biopsies (3–375 μmol g^–1) of 174 patients. The mean difference of 0.8 μmol g^–1 (95% confidence interval of –6.3 to 7.9) between this method and the biochemical analysis is quite similar [8] to the intra-individual variability found in histological samples [12].The quantitative MRI methods are based on progressive SI decay, with the longer echo times due to relaxing properties of iron. Interestingly, this iron-induced effect is seen in MR images with multiple echoes [4,6-11], but also in dual-echo images, namely in-phase and out-of-phase imaging [13,14]. In-phase and out-of-phase imaging has become a routine part of liver MRI, performed initially for liver fat detection [6,13,15]. Quite recently some investigators have noticed an alternative approach of the sequence to detect liver iron overload due to the more pronounced SI decrease on in-phase images with the longer echo time [13,14]. Yet, to our knowledge, this is the first prospective study evaluating the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration.The purpose of the study was to evaluate the capability and accuracy of dual-echo in-phase and out-of-phase imaging to assess hepatic iron concentration at 1.5 T in patients with haematological malignancies and chronic liver disease. MRI-based hepatic iron concentration (M-HIC, μmol g^–1) was used as a reference standard [8,9].     

Use of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study

Objective:

Synchronous malignancy in both breasts is a rare incidence. The present study aims at dosimetric comparison of conventional bitangential radiotherapy (RT) technique with conventional [field-in-field (FIF)] and rotational [Helical TomoTherapy® and TomoDirect™ (TD); Accuray Inc., Sunnyvale, CA] intensity-modulated RT for patients with synchronous bilateral breast cancer (SBBC).

Methods:

CT data sets of 10 patients with SBBC were selected for the present study. RT was planned for all patients on both sides to whole breast and/or chest wall using the above-mentioned techniques. Six females with breast conservation on at least one side also had a composite plan along with tumour bed (TB) boost using sequential electrons for bitangential and FIF techniques or sequential helical tomotherapy (HT) boost (for TD) or simultaneous integrated boost (SIB) for HT.

Results:

All techniques produced acceptable target coverage. The hotspot was significantly lower with FIF technique and HT but higher with TD. For the organs at risk doses, HT resulted in significant reduction of the higher dose volumes. Similarly, TD resulted in significant reduction of the mean dose to the heart and total lung by reducing the lower dose volumes. All techniques of delivering boost to the TB were comparable in terms of target coverage. HT-SIB markedly reduced mean doses to the total lung and heart by specifically lowering the higher dose volumes.

Conclusion:

This study demonstrates the cardiac and pulmonary sparing ability of tomotherapy in the setting of SBBC.

Advances in knowledge:

This is the first study demonstrating feasibility of treatment of SBBC using tomotherapy.Breast cancer is the most common malignancy amongst females in the world, including Indian females.¹ Cancer in both breasts is an uncommon presentation. Incidence of bilateral breast cancer (BBC) has been reported in the range of 1.4–11.8% with the majority being metachronous cancer.^2,3 Depending upon various definitions adopted by authors, synchronous BBC (SBBC) accounts for approximately 0.4–2.8% of all breast cancers.^4,5 Whether bilaterality confers worse prognosis or similar prognosis is yet to be conclusively determined. Some studies have indicated that there is no difference in survival between the unilateral vs BBC patient groups, while other studies claim that bilateral carcinoma significantly reduces survival.^6,7 Treatment in patients with BBC is similar to that in patients with unilateral breast cancer wherein adjuvant radiotherapy (RT) forms an integral part of the breast conservation algorithm. The safety of breast conservation surgery (BCS) for SBBC has been documented in literature.^8,9 Adjuvant RT for breast cancer typically includes whole breast irradiation after lumpectomy or chest wall irradiation after mastectomy with or without regional nodal irradiation. This is accomplished using conventional bitangential portals that include part of the anterior chest wall adjacent to the RT target.^10–12 RT delivery in cases of SBBC is even more complex owing to multiple field junctions, which results in heterogeneous dose distributions as well as significantly higher irradiation volume of organs at risk (OARs) such as the lungs and heart.The reported incidence of radiation pneumonitis (RP) varies from 0% to 80% depending upon the radiation technique, length of follow-up, imaging modality used and the end point chosen.^13–16 Although symptomatic RP is a rare clinical complication for unilateral breast cancer, it has a potential detrimental effect of reducing the normal functional reserve and should be taken into consideration given the long life expectancy of patients and higher volume of irradiation owing to bilaterality in patients with SBBC. The risk and severity of RP is influenced by various therapy-related (volume of incidentally irradiated lung, region of irradiated lung, radiation dose, fractionation and concomitant use of systemic agents, particularly paclitaxel) and patient-related factors (age, pre-existing lung disease, poor pulmonary function, smoking habits, genetic predisposition). The most significant amongst these include patient age, locoregional RT, reduced pre-RT pulmonary reserve and concomitant tamoxifen use with adjuvant RT.^17–19 These factors correlate with various dosimetric indices [V₂₀, D₂₅, mean lung dose (MLD)] that predict the risk of RP.²⁰Similarly, the toxic effect of radiation on the heart has been well documented. The long-term risk of ischaemic heart disease following breast RT has been correlated with the mean heart dose, maximum heart distance and various dosimetric parameters (V₂₀, V₃₀ and V₄₀). Moreover, several patient-related risk factors (body mass index, diabetes mellitus, dyslipidaemia, tobacco/alcohol consumption, prior heart disease) and systemic agents (anthracyclines, trastuzumab, tamoxifen) modify the risk of radiation-induced cardiac toxicity.^21,22 Patients with BBC receive a higher radiation dose to the heart (owing to scatter radiation from the right side) and would be at increased risk of radiation-induced cardiac toxicity.²³Although techniques of delivering RT have improved considerably for various sites in past two decades, the technique of delivering RT to the breast or chest wall, unilateral or bilateral, has not changed much. Various other methods have been used to deliver RT to the breast and/or the chest wall for SBBC across the world, such as electron arc therapy, or static or rotational intensity-modulated RT (IMRT), but none has been compared with conventional bitangential RT.^24,25Helical TomoTherapy® (HT) (Accuray Inc., Sunnyvale CA) is a radiation delivery modality that delivers an intensity-modulated fan beam using a 6-MV linear accelerator mounted on a ring gantry that rotates around the patient as he/she advances slowly through the gantry bore.²⁶ Dosimetric data regarding the use of HT in breast cancer treatment have resulted in equivocal results, not only in the context of target coverage and homogeneity but in the sparing of the heart and lungs as well. Although HT has been studied in the context of partial breast irradiation, whole breast irradiation and locoregional nodal irradiation,^27–30 fewer data are available on the dosimetry and feasibility of HT in the context of SBBC requiring bilateral adjuvant radiation with or without simultaneous integrated boost (SIB) of the tumour bed (TB).TomoDirect™ (TD) (Accuray Inc.) is a static or non-rotational extension of HT, which is also referred to as TomoTherapy®. In this application of TomoTherapy, the patient is translated craniocaudally through fixed gantry positions with simultaneous beam modulation. Up to 12 coplanar fixed beams can be used for dose optimization and target coverage. Similar to HT, dosimetric and clinical data are also available with TD in both, three-dimensional conformal RT (3DCRT) and/or IMRT mode for treatment of unilateral breast cancer treatment.^28,31–33 However, no data are available on the dosimetry and feasibility of TD in the context of SBBC.In our study, we aimed to compare conventional bitangential RT with conventional IMRT and two techniques of tomotherapy, namely HT and TD dosimetrically in the context of SBBC.     

Radiation pneumonitis in patients with lung and mediastinal tumours: a retrospective study of risk factors focused on pulmonary emphysema

Objectives

To evaluate the impact of pulmonary emphysema (PE) on the incidence and severity of radiation pneumonitis (RP) in patients with lung and mediastinal tumours.

Methods

92 patients were enrolled. Involved-field radiation therapy (non-small cell carcinoma or mediastinal tumours in 69 patients; median 70 Gy) and accelerated hyperfractionation (limited disease small cell carcinoma in 23 patients; median 45 Gy) were performed. Common Terminology Criteria for Adverse Events v.3.0 was used to evaluate RP and the relationship with the percentage of pulmonary volume irradiated to >20 Gy (V20) and PE. PE was diagnosed by the presence of low-attenuation areas (LAAs) on CT scans and was classified into Grades 0–4 according to the extent of the LAAs.

Results

The median follow-up time was 16 months. The 6-month cumulative incidence of RP at Grade 3 or greater was 7.7% and 34.1% in patients with a V20 of <25% and ≥25%, respectively (p=0.017). In patients with PE Grades 0, 1, 2 and 3 or greater, the incidence of RP was 16.5%, 9.1%, 8.6% and 54.0%, respectively. As the PE Grade increased, the incidence of RP also increased significantly.

Conclusion

The incidence and severity of RP are significantly higher in patients with a high V20 value as well as in those with severe PE.There has been an increase worldwide, as well as in Japan, of the prevalence of chronic obstructive pulmonary disease (COPD). It has been estimated that at least 8.6% of Japanese adults (aged >40 years) have this disease [1]. As the population ages, the incidence of COPD is expected to increase. Pulmonary emphysema (PE) is a subtype of COPD, and is defined pathologically as a group of diseases that demonstrate anatomical alterations in the lung characterised by enlargement of air spaces distal to the terminal bronchiole and accompanied by destructive changes of the alveolar walls [2]. PE is the most common subtype of COPD in Japanese patients [3]. Smoking is a common risk factor shared by patients with lung cancer and those with COPD. In patients with lung cancer who also have COPD, surgery frequently cannot be performed because of low cardiopulmonary reserve [4]. Thus, radiation therapy (RT) has been increasingly used for these patients to preserve pulmonary function.Radiation pneumonitis (RP) is one of the most significant complications for patients with lung cancer and especially for those who also have COPD. There is some consensus about the association of a few dosimetric factors and the incidence and severity of RP [5-8]. However, although COPD is considered as one of the risk factors of RP, very few investigations have included cases of clinically assessed COPD in their correlations with RP [9-11]. Moreover, the relationship between the incidence and severity of RP and with PE has not been clearly determined.The purpose of this study was to evaluate the association of PE with the incidence and severity of RP in patients with lung and mediastinal tumours.     

Correlation of the apparent diffusion coefficiency values on diffusion-weighted imaging with prognostic factors for breast cancer

Objective

The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of breast cancer with prognostic factors.

Methods

335 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) and ductal carcinoma in situ (DCIS) who underwent breast MRI with diffusion-weighted imaging were included in this study. ADC of breast cancer was calculated using two b factors (0 and 1000 s mm^–2). Mean ADCs of IDC NOS and DCIS were compared and evaluated. Among cases of IDC NOS, mean ADCs were compared with lymph node status, size and immunochemical prognostic factors using Student''s t-test. ADC was also correlated with histological grade using the Kruskal–Wallis test.

Results

Mean ADC of IDC NOS was significantly lower than that of DCIS (p<0.001). However, the mean ADC of histological grade of IDC NOS was not significantly different (p=0.564). Mean ADC of oestrogen receptor (ER)-positive or progesterone receptor (PR)-positive cancer was significantly lower than that of ER-negative or PR-negative cancer (p=0.003 vs p=0.032). Mean ADC of Ki-67 index-positive cancer was significantly lower than that of Ki-67 index-negative cancer (p=0.028). Mean ADC values of cancers with increased microvascular density (MVD) were significantly lower than those of cancer with no MVD increase (p=0.009). No correlations were observed between mean ADC value and human growth factor receptor 2 expression, tumour size and lymph node metastasis.

Conclusion

Low ADC value was correlated with positive expression of ER, PR, increased Ki-67 index, and increased MVD of breast cancer.Breast MRI is an established supplemental technique to mammography and ultrasonography for evaluation of suspicious breast lesions. Diffusion-weighted MRI (DWI) has recently been integrated into the standard breast MRI for discrimination of benign and malignant breast lesions obtained with dynamic contrast-enhanced MRI [1-13]. DWI is a non-invasive technique that represents the biological character of the mainly Brownian movement of protons in bulk water molecules in vivo. Apparent diffusion coefficient (ADC) values are quantified by measurement of mean diffusivity along three orthogonal directions, which are affected by cellularity of the tissue, fluid viscosity, membrane permeability and blood flow [7,9-11]. Microstructural characteristics, including water diffusion and blood microcirculations in capillary networks, were associated with ADC value. Decreased movement of molecules in highly cellular tissue showed correlation with a low ADC value [3,4]. Several studies of DWI of the breast have reported significantly lower ADC values in malignant tumours, compared with benign breast lesions and normal tissue [1-3,5-11,14]. Classic prognostic markers, including tumour size and grade, and lymph node status in patients with breast cancer, and molecular markers, including oestrogen receptor (ER), progesterone receptor (PR), Ki-67 index, human growth factor receptor 2 (HER2) protein and angiogenic molecular markers, have been reported [1,15,16]. Few studies have examined the correlation between ADC values and prognostic factors [1,8]. The purpose of this study is to compare ADC values of DWI of breast cancer with prognostic factors.     

Comparison of mammography, sonography, MRI and clinical examination in patients with locally advanced or inflammatory breast cancer who underwent neoadjuvant chemotherapy

Objectives

The purpose of this study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced or inflammatory breast cancer. Each prediction method was compared with the gold standard of surgical pathology.

Methods

43 patients (age range, 25–62 years; mean age, 42.7 years) with locally advanced or inflammatory breast cancer who had been treated by neoadjuvant chemotherapy were enrolled prospectively. We compared the predicted residual tumour size and the predicted response on imaging and clinical examination with residual tumour size and response on pathology. Statistical analysis was performed using weighted kappa statistics and intraclass correlation coefficients (ICC).

Results

The ICC values between predicted tumour size and pathologically determined tumour size were 0.65 for clinical examination, 0.69 for mammography, 0.78 for sonography and 0.97 for MRI. Agreement between the response predictions at mid-treatment and the responses measured by pathology had kappa values of 0.28 for clinical examination, 0.32 for mammography, 0.46 for sonography and 0.68 for MRI. Agreement between the final response predictions and the responses measured by pathology had kappa values of 0.43 for clinical examination, 0.44 for mammography, 0.50 for sonography and 0.82 for MRI.

Conclusion

Predictions of response and residual tumour size made on MRI were better correlated with the assessments of response and residual tumour size made upon pathology than were predictions made on the basis of clinical examination, mammography or sonography. Thus, the evaluation of predicted response using MRI could provide a relatively sensitive early assessment of chemotherapy efficacy.The advantages of neoadjuvant chemotherapy are multiple and it has been used widely during the past few years [1]. Its primary role is to induce tumour shrinkage and permit breast-conserving surgery, primarily in patients with advanced breast cancer [2-4]. Neoadjuvant chemotherapy allows earlier treatment of micrometastatic disease and the study of biological markers that might predict tumour response [5]. The effectiveness of chemotherapeutic agents in treating both primary breast cancer and potential metastatic disease may be enhanced by the presence of tumour neovascularity. If chemotherapy is given before surgery, while tumour vascularity remains intact, the chemotherapeutic agents may be better able to reach the tumour and thus be more effective.Neoadjuvant chemotherapy of locally advanced breast cancer (LABC) has also been shown to improve the resectability rate, offering disease-free and overall survival rates that are at least equivalent to those offered by surgery alone [6,7]. Pathological complete response (pCR) is clinically significant because it is associated with improved long-term prognosis and decreased risk of recurrence [6,8]. Decisions regarding the continuation of current regimens and the appropriate type and timing of surgery depend on the radiological and clinical assessment of residual tumour size during neoadjuvant chemotherapy [9,10]. Until now, many studies have shown that physical examinations, mammography and sonography provide suboptimal evaluations of lesion extent that do not allow accurate assessments of pathological response or residual tumour size [5^,11-13]. In the case of LABC, physical examination, mammography or sonography may be suitable for detecting the larger lesions of non-responders, but they have limited sensitivity for responders with smaller residual lesions [14,15]. For mammography, calcifications may persist or even increase in patients who respond to neoadjuvant chemotherapy [14,16,17].Many previous studies have shown that MRI is the most reliable technique for evaluating residual disease after neoadjuvant chemotherapy, although initial reports described frequent false-negatives with smaller-volume disease [18-27]. Recent studies have increased the sensitivity of MRI, with increased resolution, reduced slice thickness and lower enhancement thresholds being used to minimise the underestimation of residual disease [15^,22-27]. It is still difficult, however, to distinguish residual scarring, necrosis and fibrosis from viable residual malignancy and to predict accurate response after neoadjuvant chemotherapy, especially in responders. Few published studies have described work with patients with inflammatory breast cancer who underwent neoadjuvant chemotherapy because the incidence of this disease is very low [28,29]. The purpose of our study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced and inflammatory breast cancer. We compared each prediction method with the gold standard of surgical pathology.     

Primary vaginal cancer: role of MRI in diagnosis,staging and treatment

Primary carcinoma of the vagina is rare, accounting for 1–3% of all gynaecological malignancies. MRI has an increasing role in diagnosis, staging, treatment and assessment of complications in gynaecologic malignancy. In this review, we illustrate the utility of MRI in patients with primary vaginal cancer and highlight key aspects of staging, treatment, recurrence and complications.The incidence of primary vaginal cancer increases with age, with approximately 50% of patients presenting at age greater than 70 years and 20% greater than 80 years.¹ Around 2890 patients are currently diagnosed with vaginal carcinoma in the USA each year, and almost 30% die of the disease.² The precursor for vaginal cancer, vaginal intraepithelial neoplasia (VAIN) and invasive vaginal cancer is strongly associated with human papillomavirus (HPV) infection (93%).^3,4 In situ and invasive vaginal cancer share many of the same risk factors as cervical cancer, such as tobacco use, younger age at coitarche, HPV and multiple sexual partners.^5–7 In fact, higher rates of vaginal cancer are observed in patients with a previous diagnosis of cervical cancer or cervical intraepithelial neoplasia.^7,8As is true for other gynaecologic malignancies, vaginal cancer diagnosis and staging rely primarily on clinical evaluation by the International Federation of Gynecology and Obstetrics (FIGO).⁹ Pelvic examination continues to be the most important tool for evaluating local extent of disease, but this method alone is limited in its ability to detect lymphadenopathy and the extent of tumour infiltration. Hence, FIGO encourages the use of imaging. Fluorine-18 fludeoxyglucose-positron emission tomography (¹⁸F-FDG-PET), a standard imaging tool for staging and follow-up in cervical cancer, can also be used for vaginal tumours, with improved sensitivity for nodal involvement compared to CT alone.¹⁰ In addition to staging for nodal and distant disease, CT [simulation with three dimensional (3D) conformations] is particularly useful for treatment planning and delivery of external beam radiation. MRI, with its excellent soft tissue resolution, is commonly used in gynaecologic malignancies and has been shown to be accurate in diagnosis, local staging and spread of disease in vaginal cancer.^11,12 While no formal studies are available for vaginal cancer, in cervical cancer MRI actually alters the stage in almost 30% of patients.^13–15Treatment planning in primary vaginal cancer is complex and requires a detailed understanding of the extent of disease. Because vaginal cancer is rare, treatment plans remain less well defined, often individualized and extrapolated from institutional experience and outcomes in cervical cancer.^1,16–19 There is an increasing trend towards organ preservation and treatment strategies based on combined external beam radiation and brachytherapy, often with concurrent chemotherapy,^14,20,21 surgery being reserved for those with in situ or very early-stage disease.²² Increasing utilization of MR may provide superior delineation of tumour volume, both for initial staging and follow-up, to allow for better treatment planning.²³     

Towards clinical assessment of velopharyngeal closure using MRI: evaluation of real-time MRI sequences at 1.5 and 3 T

Objective

The objective of this study was to demonstrate soft palate MRI at 1.5 and 3 T with high temporal resolution on clinical scanners.

Methods

Six volunteers were imaged while speaking, using both four real-time steady-state free-precession (SSFP) sequences at 3 T and four balanced SSFP (bSSFP) at 1.5 T. Temporal resolution was 9–20 frames s⁻¹ (fps), spatial resolution 1.6×1.6×10.0–2.7×2.7×10.0 mm³. Simultaneous audio was recorded. Signal-to-noise ratio (SNR), palate thickness and image quality score (1–4, non-diagnostic–excellent) were evaluated.

Results

SNR was higher at 3 T than 1.5 T in the relaxed palate (nasal breathing position) and reduced in the elevated palate at 3 T, but not 1.5 T. Image quality was not significantly different between field strengths or sequences (p=NS). At 3 T, 40% acquisitions scored 2 and 56% scored 3. Most 1.5 T acquisitions scored 1 (19%) or 4 (46%). Image quality was more dependent on subject or field than sequence. SNR in static images was highest with 1.9×1.9×10.0 mm³ resolution (10 fps) and measured palate thickness was similar (p=NS) to that at the highest resolution (1.6×1.6×10.0 mm³). SNR in intensity–time plots through the soft palate was highest with 2.7×2.7×10.0 mm³ resolution (20 fps).

Conclusions

At 3 T, SSFP images are of a reliable quality, but 1.5 T bSSFP images are often better. For geometric measurements, temporal should be traded for spatial resolution (1.9×1.9×10.0 mm³, 10 fps). For assessment of motion, temporal should be prioritised over spatial resolution (2.7×2.7×10.0 mm³, 20 fps).

Advances in knowledge

Diagnostic quality real-time soft palate MRI is possible using clinical scanners and optimised protocols have been developed. 3 T SSFP imaging is reliable, but 1.5 T bSSFP often produces better images.Approximately 450 babies born in the UK every year have an orofacial cleft [1], the majority of which include the palate [2]. While a cleft palate is commonly repaired surgically at around 6 months [3], residual velopharyngeal insufficiencies require follow-up surgery in 15–50% of cases [4]. This residual defect results in an incomplete closure of the velopharyngeal port, which in turns leads to hypernasal speech. Assessment of velopharyngeal closure in speech therapy is commonly performed using X-ray videofluoroscopy or nasendoscopy [5,6]. While nasendoscopy is only minimally invasive, it may be uncomfortable and provides only an en face view of the velopharyngeal port. In contrast, X-ray videofluoroscopy is non-invasive and produces an image which is a projection of the target anatomy. Additional information may be obtained from projections at multiple angles [5,7], but anatomical structures may overlie each other. Furthermore, soft tissue contrast, such as that from the soft palate, is poor, although it may be improved using a barium contrast agent coating [8] at the expense of making the procedure more invasive and unpleasant. Arguably the greatest drawback of X-ray videofluoroscopy is the associated ionising radiation dose, which carries increased risk in paediatric patients [9].An increasing number of research studies have used MRI to image the soft palate [10-13] and upper vocal tract [14-17]. In contrast to X-ray videofluoroscopy and nasendoscopy, MRI provides tomographic images in any plane with flexible tissue contrast. As a result, MRI has been used to obtain images of the musculature of the palate at rest and during sustained phonation [10,18,19]. It has also been used to image the whole vocal tract at rest or during sustained phonation [20-27] and with a single mid-sagittal image dynamically during speech [13,15-17,28-35].For assessment of velopharyngeal closure, dynamic imaging with sufficient temporal resolution and simultaneous audio recording is required. Audio recording during imaging is complicated by the loud noise of the MRI scanner, and both the safety risk and image degradation caused by using an electronic microphone within the magnet. As a result, optical fibre-based equipment with noise cancellation algorithms must be used [36].In order to fully resolve soft palate motion, Narayanan et al [30] suggested that a minimum temporal resolution of 20 frames s⁻¹ (fps) is required. A similar conclusion was reached by Bae et al [13], based on measurements of soft palate motion extracted from X-ray videofluoroscopy. Using segmented MRI, Inoue et al [35] demonstrated that changes in the velar position that were evident at acquired frame rates of 33 fps were not observed at 8 fps. However, MRI is traditionally seen as a slow imaging modality and achieving sufficient temporal resolution at an acceptable spatial resolution is challenging. Furthermore, as the soft palate is bordered on both sides by air, the associated changes in magnetic susceptibility at the interfaces make images prone to related artefacts.Dynamic MRI of the vocal tract has been performed using both segmented [17,33,37] and real-time acquisitions [13,15,16,28,31,38]. Segmented acquisitions [39] acquire only a fraction of the k-space data required for each image during one repetition of the test phrase and, hence, require multiple identical repetitions. While these segmented techniques permit high temporal and spatial resolutions [35], they require reproducible production of the same phrase up to 256 times [34], leading to subject fatigue. Differences between repeats of up to 95 ms in the onset of speech following a trigger have also been demonstrated [36].In contrast to segmented techniques, real-time dynamic methods permit imaging of natural speech, but require extremely rapid acquisition and often advanced reconstruction methods. The turbo spin echo (TSE) zoom technique [40] has been used to perform real-time MRI of the vocal tract [29,31] and is available as a clinical tool. The zoom technique excites a reduced field of view in the phase encode direction, hence allowing a smaller acquisition matrix and shorter scan for a constant spatial resolution. While such spin echo-based techniques are less susceptible to magnetic field inhomogeneity related signal dropout artefacts than other sequences, the frame rates achieved with these sequences are limited to 6 fps [31]. Gradient echo-based techniques have also been used to achieve similar temporal resolution [12,41,42] in the upper vocal tract, but are often used at much higher frame rates in other MRI applications such as cardiac imaging [43,44]. A number of gradient echo sequence variants exist. Fast low-angle shot (FLASH) type sequences [45] spoil any remaining transverse magnetisation at the end of every sequence repetition (TR). In contrast, steady-state free-precession (SSFP) sequences are not spoiled [46] and the remaining transverse magnetisation is used in the next TR to improve the signal-to-noise ratio (SNR), but renders the images sensitive to signal loss in the presence of motion. Balanced SSFP (bSSFP) sequences include additional gradients to bring the transverse magnetisation completely back into phase at the end of every TR [47,48]. The result is that bSSFP sequences have high SNR and are less sensitive to motion than SSFP sequences, but are more sensitive to field inhomogeneities, which cause bands of signal dropout.Both TSE and the gradient echo techniques discussed here sample in a rectilinear or Cartesian fashion, where one line of k-space is sampled in each echo. However, for real-time speech imaging, the highest acquired frame rates have been achieved by sampling k-space along a spiral trajectory [15,16,30,49]. While spiral imaging is an efficient way to sample k-space and is motion-resilient, it is prone to artefacts, particularly blurring caused by magnetic field inhomogeneities and off-resonance protons (i.e. fat) [50]. Recently, one group successfully used spiral imaging with multiple saturation bands and an alternating echo time (TE) to achieve an acquired real-time frame rate of 22 fps [13,16]. The saturation bands were used to allow a small field of view to be imaged without aliasing artefacts. The alternating TE was used to generate dynamic field maps which were incorporated into the reconstruction to compensate for magnetic field inhomogeneities. However, such advanced acquisition and reconstruction techniques are only available in a small number of research centres.The aim of this work is to optimise and demonstrate high-temporal-resolution real-time sequences available on routine clinical MRI scanners for assessment of soft palate motion and velopharyngeal closure. Consequently, radial and spiral acquisitions were excluded and the work focuses on Cartesian gradient echo sequences with parallel imaging techniques. As more clinical MRI departments now have 3 T scanners, imaging was performed at both 1.5 and 3 T to enable comparisons. At each field strength, we optimised sequences and implemented four combinations of spatial and temporal resolution in six subjects with simultaneous audio recordings.     

MRI features of serous oligocystic adenoma of the pancreas: differentiation from mucinous cystic neoplasm of the pancreas

Objectives

The purpose of this study was to describe the MRI features of the benign pancreatic neoplasm serous oligocystic adenoma (SOA) that differ from those of mucinous cystic neoplasm (MCN), a neoplasm with the potential for malignant degeneration.

Methods

Seven patients with SOA (seven women; mean age 36.6 years) and eight patients with MCN (eight women: mean age 39.9 years) were included. Several imaging features were reviewed: mass size, location, shape, wall thickness, cyst configuration (Type I, unilocular; Type II, multiple clustered cyst; Type III, cyst with internal septation) and signal intensity of the lesion with heterogeneity.

Results

SOA lesions were smaller (3.4 cm) than those of MCN (9.3 cm) (p=0.023). The commonest lesion shape was lobulated (85.7%) for SOA, but oval (50.0%) or lobulated (37.5%) for MCN (p=0.015). The most common cyst configuration was Type II (85.7%) for SOA and Type III (75.0%) for MCN (p=0.008). Heterogeneity of each locule in T₁ weighted images was visible in all cases of MCN, but in no case for SOA (p=0.004).

Conclusion

SOA could be differentiated from MCN by identifying the imaging features of lobulated contour with multiple clustered cyst configurations and homogeneity of each locule in T₁ weighted MR images.Serous oligocystic adenoma (SOA) is a recently described rare, benign pancreatic neoplasm and a morphological variant of serous microcystic adenoma, because it contains six or fewer cysts and the cysts are large (>2 cm) [1,2]. Pathologically, SOA is a benign pancreatic neoplasm composed of a few relatively large cysts uniformly lined with glycogen-rich cuboidal epithelial cells [3]. According to the World Health Organization classification, SOA is a subgroup of pancreatic serous cystic tumours and the term SOA is a synonym for macrocystic serous cystadenoma [3,4].The CT and MRI features of SOA of the pancreas are documented [2]. On CT and MRI, SOA typically appears as a small unilocular or bilocular cyst (<5 cm) with a thin wall (<2 mm) that lacks mural nodules or calcifications [2]. Because the cystic spaces are >2 cm, SOA images can be mistaken for mucinous cystic neoplasm (MCN), pseudocyst or intraductal papillary mucinous tumour [2,5-7]. It is very difficult to differentiate SOA from MCN by clinical and radiological features [2,6,8,9]. SOA does not require resection unless it causes symptoms, but MCN should be resected because of a potential for malignant degeneration [5,7,8]. Endoscopic ultrasound and cyst fluid aspiration have a role in distinguishing mucinous and serous lesions, but it is an invasive procedure with a risk of complications such as pancreatitis [10]. Therefore, it is clinically valuable to determine characteristic imaging findings that can distinguish SOA from MCN.Recently, Kim et al [6] and Cohen-Scali et al [5] described characteristic CT findings that can be used to differentiate SOA from MCN. MRI can demonstrate septa within a lesion with greater sensitivity than CT; therefore, MRI provides a better evaluation of tissue characteristics than CT [1,11]. However, few studies have described the MRI features of SOA [1,2]. The purpose of this study was to describe the differences in the MRI features of SOA and MCN in the pancreas.     

Non-osseous incidental findings in low-dose whole-body CT in patients with multiple myeloma

Objective:

The purpose of this study was to identify the frequency and grading of non-osseous incidental findings (NOIF) in non-contrast whole-body low-dose CT (LDCT) in patients with multiple myeloma.

Methods:

In the time period from 2010 to 2013, 93 patients with multiple myeloma were staged by non-contrast whole-body LDCT at our radiological department. LDCT images were analysed retrospectively for NOIF, which also included unsuspected extramedullary manifestation of multiple myeloma. All NOIF were classified as major or clinically significant, moderate or possibly clinically significant and minor or not clinically significant. Medical records were analysed regarding further investigation and follow-up of the identified NOIF.

Results:

In the 93 patients, 295 NOIF were identified (on average, 3.2 NOIF per patient). Most of the NOIF (52.4%) were not clinically significant, 25.8% of the NOIF were possibly clinically significant and 21.8% of the NOIF were clinically significant. Clinically significant NOIF were investigated further by CT after intravenous administration of contrast medium and/or by ultrasound or MRI. In 34 of these cases, extramedullary relapse of myeloma, occult carcinoma or infectious/septic incidental findings were diagnosed (11.5% of all NOIF). In the remaining 10.3% of the NOIF classified as clinically significant, various benign lesions were diagnosed.

Conclusion:

LDCT detected various non-osseous lesions in patients with multiple myeloma. 36.6% of the patients had clinically significant NOIF. Therefore, LDCT examinations in patients with multiple myeloma should be evaluated carefully for the presence of NOIF.

Advances in knowledge:

LDCT identified several NOIF. A total of 36.6% of patients with multiple myeloma had clinically significant NOIF. Radiologists should analyse LDCT examinations in patients with multiple myeloma not only for bone lesions, but also for lesions in other organs.CT is used for screening or staging in several malignancies.^1–8 As reported previously, the staging CT examination also provides additional information regarding the general health status of the patient or so-called incidental findings (IF).^1,3,6,7 Several IF on CT examinations were described in the literature.^1–6 According to previous reports, IF can be classified into five different categories: Group “0”, limited examination, that is, evaluation of IF are severely limited; Group “1”, normal findings or anatomic variant; Group “2”, clinically unimportant findings, such as liver or kidney cysts; Group “3”, likely unimportant findings; and Group “4”, potentially important findings, such as solid renal masses or lymphadenopathy.⁵ In another publication, a three-part classification of IF according to their clinical importance was proposed, namely major, moderate and minor IF.¹Most of the IF are clinically non-significant, such as colonic diverticula or simple cysts.^1–7 However, serious IF, such as aortic aneurysm or dissection, thrombosis, pulmonary embolism and second primary tumours, can also occur,^1,3,6,7 and some of them may be not visible on low-dose CT (LDCT).Most reports regarding IF are based on contrast-enhanced CT.^1,7,9–11 There are only a few reports regarding IF in LDCT.¹² They described IF in screening programmes for lung cancer and based the findings on thoracic LDCT only.¹² In addition, non-contrast LDCT has been established for staging of bone lesions in multiple myeloma.^13–16 However, radiologists should analyse LDCT examinations not only for bone lesions but also for lesions in other organs, which may include extramedullary manifestation of multiple myeloma as well as unrelated IF.Although IF in multiple myeloma have also been described previously,¹⁴ to the best of our knowledge, there exists no analysis focused on frequency and distribution of non-osseous IF (NOIF) on whole-body LDCT. Therefore, the purpose of this study was to identify the frequency and grading of NOIF in non-contrast whole-body LDCT in patients with multiple myeloma.     

Correlation between mammographic and sonographic findings and prognostic factors in patients with node-negative invasive breast cancer

Objectives

The purpose of this study was to correlate sonographic and mammographic findings with prognostic factors in patients with node-negative invasive breast cancer.

Methods

Sonographic and mammographic findings in 710 consecutive patients (age range 21–81 years; mean age 49 years) with 715 node-negative invasive breast cancers were retrospectively evaluated. Pathology reports relating to tumour size, histological grade, lymphovascular invasion (LVI), extensive intraductal component (EIC), oestrogen receptor (ER) status and HER-2/neu status were reviewed and correlated with the imaging findings. Statistical analysis was performed using logistic regression analysis and intraclass correlation coefficient (ICC).

Results

On mammography, non-spiculated masses with calcifications were associated with all poor prognostic factors: high histological grade, positive LVI, EIC, HER-2/neu status and negative ER. Other lesions were associated with none of these poor prognostic factors. Hyperdense masses on mammography, the presence of mixed echogenicity, posterior enhancement, calcifications in-or-out of masses and diffusely increased vascularity on sonography were associated with high histological grade and negative ER. Associated calcifications on both mammograms and sonograms were correlated with EIC and HER-2/neu overexpression. The ICC value for the disease extent was 0.60 on mammography and 0.70 on sonography.

Conclusion

Several sonographic and mammographic features can have a prognostic value in the subsequent treatment of patients with node-negative invasive breast cancer. Radiologists should pay more attention to masses that are associated with calcifications because on both mammography and sonography associated calcifications were predictors of positive EIC and HER-2/neu overexpression.The three strongest prognostic factors in invasive breast cancer are widely accepted to be lymph node stage, histological grade and the size of histologically invasive cancer [1–4]. Axillary lymph node stage is an important prognostic factor in invasive breast cancer: the prognosis progressively worsens with an increasing number of involved nodes. Although controversial, micrometastatic disease continues to have clinical significance. Most series have shown that nodal micrometastasis appears to have a more or less adverse effect on disease-g0ree and overall survival [5]. The three strongest prognostic factors in invasive breast cancer provide more valuable information when taken into account altogether than when any single individual factor is used alone. The Nottingham Prognostic Index (NPI) uses these three factors and has been externally validated by several studies [2, 6–8]. In addition, histological grade, tumour size and oestrogen receptor (ER) status are usually used as significant factors in guiding adjuvant systemic chemotherapy in node-negative patients [9].Lymphovascular invasion (LVI) shows a clear relationship with nodal status [10–13] and local recurrence [12, 13]. LVI is also related to distant metastasis and overall survival in node-negative breast cancer [14, 15]. Patients with breast cancers that exhibit a high proportion of intraductal components have a higher risk of local recurrence after conservative surgery [16, 17]. Hence, accurate evaluation of intraductal spread is considered to be a key issue in determining tumour margins before planning breast-conserving surgery [18]. HER-2/neu overexpression in node-negative cancers is related to disease relapse and to disease-related death, regardless of tumour size, histological grade and ER status [19].In terms of treatment, most patients with node-positive invasive breast cancers measuring greater than 2 mm are offered adjuvant chemotherapy, with additional hormone therapy or trastuzumab (Herceptin) based upon necessity according to their hormone receptor and HER-2/neu status. On the other hand, patients with node-negative invasive cancer might not be offered adjuvant therapy, adjuvant hormone therapy or chemotherapy depending on the size, LVI, histological grade, their hormone receptor responsiveness and HER-2/neu status, and their age [20]. Therefore, in patients with node-negative breast cancers, knowing the hormone receptor and HER-2/neu status, histological grade and extent of LVI is very important in guiding the treatment plan and determining the prognosis.Several studies have looked at the correlation between imaging findings and prognostic factors [18, 21–27]. To our knowledge, however, no report has correlated imaging findings in node-negative invasive breast cancers that were analysed according to the Breast Imaging Report and Data System (BI-RADS) lexicon with prognostic factors. The purpose of our study was to correlate sonographic and mammographic findings with prognostic factors in patients with node-negative invasive breast cancer and to determine whether or not the imaging findings could have prognostic value. We also determined the relative accuracy of mammography and sonography in evaluating the extent of disease in patients with node-negative invasive breast cancer.