Monitoring breast cancer response to neoadjuvant chemotherapy with ultrasound signal statistics and integrated backscatter

Monitoring Neoadjuvant chemotherapy (NAC) effects is necessary to capture resistant patients and stop or change treatment. The aim of this study was to assess the tumor response at an early stage, after the first doses of the NAC, based on the variability of the backscattered ultrasound energy, and backscatter statistics. The backscatter statistics has not previously been used to monitor NAC effects. The B-mode ultrasound images and raw radio frequency data from breast tumors were obtained using an ultrasound scanner before chemotherapy and 1 week after each NAC cycle. Twenty-four malignant breast cancers, qualified for neoadjuvant treatment before surgery, were included in the study. The shape parameter of the homodyned K distribution and integrated backscatter, along with the tumor size in the longest dimension, were determined based on ultrasound data and used as markers for NAC response. Cancer tumors were assigned to responding and non-responding groups, according to histopathological evaluation, which was a reference in assessing the utility of markers. Statistical analysis was performed to rate the ability of markers to predict NAC response based on data obtained after subsequent therapeutic doses. Statistically significant differences between groups were obtained after 2, 3, 4, and 5 doses of NAC for quantitative ultrasound markers and after 5 doses for the assessment based on maximum tumor dimension. After the second and third NAC courses the marker, which was a linear combination of both quantitative ultrasound parameters, was characterized by an AUC of 0.82 and 0.91, respectively. The introduction of statistical parameters of ultrasonic backscatter to monitor the effects of chemotherapy can increase the effectiveness of monitoring and contribute to a better personalization of NAC therapy

Breast ultrasound scans – surgeons' expectations

Recent years have witnessed a dynamic development of mammary gland imaging techniques,particularly ultrasonography and magnetic resonance imaging. A challengerelated to these studies is the increase in the precision of the anatomical assessment of breast, particularly for early detection of subclinical lesions, performance of ultrasound-guided biopsy procedures, and accurate preoperative location of pathological lesions so as to optimize the surgical treatment. Ultrasound imaging is a primary and baseline diagnostic procedure the patient with suspected pathological lesions withinbreast is referred to by the surgeon. Lesions visualized in ultrasound scans are classified according to the BI-RADS US assessment categories. The successive categories (2 through 6) encompass individual pathological lesions, estimating the risk of malignancy and provide guidelines for further diagnostic and therapeutic management. This article described the important aspects of ultrasonographic imaging of focal lesions within the breasts as signifi cant from the standpoint of surgical treatment of patients falling within BI-RADS US categories 3, 4, 5, and 6. Attention is drawn to the importance of ultrasound scans in the assessment of axillary fossa lymph nodes before the decision regarding the surgical treatment

Różnicowanie zmian ogniskowych w wolu guzkowym tarczycy z zastosowaniem nowych technik ultrasonograficznych — doniesienia wstępne

  Introduction: To evaluate the relative value of technical ultrasound advances in differentiation of thyroid nodules in multinodular goitre. Material and methods: The study included patients with multinodular goitre, who were referred for thyroidectomy. Ultrasound evaluation of suspicious nodules was performed with: improved B-mode (spatial compound imaging and differential tissue harmonics), dedicated mapping of microcalcifications, mapping of the nodule vessels, and strain elastography evaluated qualitatively and semi quantitatively. Results: A total of 163 nodules in 124 patients with multinodular goitre were evaluated (147 benign and 16 cancers). Improved B-mode imaging was: 76.76% sensitive and 62.5% specific with AUC 0.740. Differentiating B-mode features were: shape — taller than wide OR 15.8, markedly hypoechoic OR 14.7, absence of cystic areas OR 6.6, absence of halo OR 5.0, and blurred/microlobulated margins OR 3.7. Addition of MicroPure imaging was 80.28% sensitive and 68.75% specific with AUC 0.771. MicroPure alone, power Doppler, and strain elastography were not statistically significant. Conclusions: Among singular modes of ultrasound imaging, only improved B-mode imaging proved to have a significant role in differentiation of thyroid nodules in multinodular goitre. Additional gain was seen with the addition to B-mode of the mapping of microcalcifications with MicroPure imaging. Power Doppler and strain elastography did not prove to be useful techniques in multinodular goitre. (Endokrynol Pol 2016; 67 (2): 157–165)    Wstęp: Celem pracy była ocena względnej wartości nowych technik ultrasonograficznych w różnicowaniu zmian ogniskowych w wolu guzkowym. Materiał i metody: Grupa badana obejmowała chorych z wolem guzkowym przed planowaną tyreoidektomią. Protokół badania ultrasonograficznego obejmował: B-mode z użyciem obrazowania złożonego przestrzennie oraz tkankowego obrazowania harmonicznego, mapowanie mikrozwapnień, mapowanie naczyń oraz elastogafię odkształceń względnych (ocena jakościowa i półilościowa). Wyniki: Oceniono w sumie 163 zmiany ogniskowe u 124 pacjentów (147 zmian łagodnych i 16 raków). Czułość, swoistość i AUC dla B-mode z użyciem obrazowania złożonego przestrzennie oraz tkankowego obrazowania harmonicznego wynosiły odpowiednio 76,76%, 62,5% oraz 0,740. Wśród ocenionych cech obrazowania B-mode różnicującymi okazały się być: kształt (zmian wyższa niż szersza OR 15,8), bardzo niska echogeniczność OR 14,7, brak zwyrodnień płynowych OR 6,6, brak otoczki halo OR 5,0 oraz zatarte/zrazikowe granice OR 3,7. Wzbogacenie obrazowania B-mode o obrazowanie Micropure zwiększyło czułość 80,28% i swoistość 68,75%, AUC 0,771. Obrazowanie Micropure, Power Doppler oraz elastografia odkształceń względnych jako samodzielne metody okazały się być nie istotne statystycznie w różnicowaniu zmian łagodnych i złośliwych. Wnioski: Wśród pojedynczych metod ultrasonograficznych jedynie wzbogacone obrazowanie B-mode okazało się być istotne w różnicowaniu zmian ogniskowych w wolu guzkowym tarczycy. Dodatkowym zyskiem było dołączenie do oceny B-mode mapowanie mikrozwapnień z zastosowaniem techniki Micropure. Power Doppler oraz elastografia odkształceń względnych okazały się być nieprzydatne w różnicowaniu zmian ogniskowych w wolu guzkowym tarczycy. (Endokrynol Pol 2016; 67 (2): 157–165)

Integration of Sonoelastography Into the TIRADS Lexicon Could Influence the Classification

Aim: Numerous TIRADS (Thyroid Image Reporting and Data System) classifications have been developed, and various ultrasound (US) parameters are employed in different countries. The aim of our study was to introduce risk classification and management in a native population based on the Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma but with the addition of sonoelastography.Materials and Methods: We examined prospectively 208 patients with 305 thyroid lesions employing B-mode ultrasound and sonoelastography (SE). Nodule composition, echogenicity, margins, shape, presence or absence of calcifications, thyroid capsule, nodule size were assessed using B-mode ultrasound. Moreover, sonoelastography results were presented using the Asteria scale.Results: In univariate analysis, the following US features were significantly associated with malignancy: >50% solid /solid component, marked hypoechogenicity, ill-defined margins, micro and macrocalcification, taller-than wide shape, no/partial halo pattern, infiltration of the capsule and an Asteria score of 4. Multivariate logistic regression analysis of B-mode features revealed that ill-defined margins (OR 10.77), markedly hypoechogenicity (OR 5.12), microcalcifications (OR 4.85), thyroid capsule infiltrations (OR 3.2), macrocalcifications (OR 3.01), and hard lesion in SE (OR 6.85) were associated with a higher Odds Ratio (OR) for malignancy. Multivariate logistic regression analysis revealed that combining two features increases the OR and the best combination was irregular margins and Asteria scale 4 (OR 20.21). Adding a third feature did not increase the OR.Conclusions: Sonoelastography increases the value risk of predicted malignancy, with consequent different approach to further clinical investigation and management. A solitary feature (Asteria 4) in a solid tumor can result in its categorization as TIRADS 4, but coexistence with high risk features allows it to be upgraded to TIRADS 5. The irregular margin was the strongest single feature which allowed for the assignment of a solid tumor into TIRADS 5 category. The highest accuracy was found by combining the features of age, margin, echogenicity (markedly hypoechoic), capsule infiltration, microcalcifications and sonoelastography (Asteria 3,4) of the tumors

The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part I: The diagnostic value of the ultrasound B-mode imaging in the differentiation diagnostics of solid, focal lesions in the breast in relation to the pathomorphological verification

The aim of this study was to evaluate the diagnostic value of the ultrasound B-mode imaging in the differentiation diagnostics of solid lesions in the breast in relation to the pathomorphological verification. From January to July 2010, 375 ultrasound breast examinations were conducted. The study enrolled 80 women aged 17–83, with 99 solid, focal lesions present in breasts, which were qualified for pathomorphological verification on the basis of the ultrasound examination. All patients underwent: the interview, physical examination, ultrasound examination and sonoelastography. The ultrasound features of the lesions, their vascularization patterns in the Doppler examination as well as the adjacent tissues were determined. Next, the focal lesions were categorized according to the BIRADS-US classification. The obtained results were analyzed statistically. In the group of 80 patients, 99 focal, solid lesions in breasts were visualized, including 39 neoplastic, malignant lesions (group I) and 60 lesions of benign nature (group II). The malignant lesions were often characterized by: greater size, irregular shape (34/39), prevalence of the anteroposterior dimension over the lateral‑lateral dimension (22/39), acoustic shadowing (20/39), the margins not well-circumscribed (37/39), spiculated margins (16/39) and the presence of calcifications (14/39). The benign lesions were much more often hyper- and isoechogenic (14/60). In group I the lesions more often demonstrated the features of increased vascularization (29/39) and the presence of irregularly shaped vessels (23/29). This vascularization more often originated in the adjacent tissues. In the surroundings of the malignant neoplastic lesions, the presence of edema (16/39) and skin thickening (6/39) occurred more frequently and the abnormal axillary lymph nodes were more often diagnosed. The lesions of group I were assigned to the following BIRADS categories: BIRADS-US 4 (9 lesions) and BIRADS-US 5 (30 lesions). In group II, there was a prevalence of BIRADS-US 3 and 4 categories (58 lesions) and 2 lesions were classified to BIRADS-US 5 category. In the statistical analysis of the models based on BIRADS classification, it was demonstrated that BIRADS 4 showed the highest sum of sensitivity and specificity values of 173.6% in differentiation of the character of focal lesions in the breast (sensitivity 76.92%, specificity 96.67%).Celem pracy była ocena wartości diagnostycznej badania ultrasonograficznego B‑mode w diagnostyce różnicowej litych zmian ogniskowych w piersiach, w odniesieniu do weryfikacji patomorfologicznej. W okresie od stycznia do lipca 2010 roku przeprowadzono 375 badań ultrasonograficznych piersi. Do badań zakwalifikowano 80 kobiet w wieku od 17 do 83 lat, z obecnością 99 litych zmian ogniskowych w piersiach, u których na podstawie badania ultrasonograficznego ustalono wskazania do weryfikacji patomorfologicznej. U wszystkich pacjentek wykonano: badanie podmiotowe i przedmiotowe, badanie ultrasonograficzne i sonoelastografię. Określano cechy obrazu ultrasonograficznego badanych zmian, ich wzorce unaczynienia w badaniu dopplerowskim oraz tkanki otaczające. Następnie zmianom ogniskowym przydzielano kategorie klasyfikacji BIRADS‑usg. Uzyskane wyniki badań poddano analizie statystycznej. W grupie 80 pacjentek uwidoczniono 99 litych zmian ogniskowych w piersiach, w tym 39 zmian nowotworowych złośliwych (grupa I) i 60 o charakterze łagodnym (grupa II). Zmiany nowotworowe złośliwe znamiennie częściej cechowały się: większymi wymiarami, nieregularnym kształtem (34/39), przewagą wymiaru przednio‑tylnego nad boczno‑bocznym (22/39), obecnością cienia akustycznego (20/39), niewyraźnie odgraniczonych brzegów (37/39), spikularnych (16/39), obecnością zwapnień (14/39). Zmiany łagodne istotnie częściej były hiper‑ i izoechogeniczne (14/60). W grupie I zmiany częściej wykazywały cechy wzmożonego unaczynienia (29/39) oraz obecność naczyń o przebiegu nieregularnym (23/29). Unaczynienie to częściej pochodziło z tkanek otaczających. W otoczeniu zmian nowotworowych złośliwych częściej obserwowano obecność obrzęku (16/39), pogrubienia skóry (6/39), częściej stwierdzano nieprawidłowe węzły chłonne pachowe. Zmianom w grupie I przydzielono kategorie BIRADS‑usg 4 (9 zmian) i BIRADS‑usg 5 (30 zmian). W grupie II dominowały zmiany w kategorii BIRADS‑usg 3 i 4 (58 zmiany), a 2 zmiany przydzielono do kategorii BIRADS‑usg 5. W analizie statystycznej modeli opartych na klasyfikacji BIRADS wykazano, iż BIRADS 4 uzyskał najwyższą wartość sumy czułości i swoistości, wynoszącą 173,6% (czułość 76,92%, swoistość 96,67%) w różnicowaniu charakteru zmian ogniskowych w piersiach

The differentiation of the character of solid lesions in the breast in the compression sonoelastography. Part II: Diagnostic value of BIRADS-US classification, Tsukuba score and FLR ratio

Sonoelastography is a dynamically developing method of ultrasound examination used to differentiate the character of focal lesions in the breasts. The aim of the Part II of the study is to determine the usefulness of sonoelastography in the differentiation diagnosis of focal breast lesions including the evaluation of the diagnostic value of Tsukuba score and FLR ratio in characterizing solid lesions in the breasts. Furthermore, the paper provides a comparison of classic B-mode imaging and sonoelastography. Material and methods: From January to July 2010 in the Ultrasound Department of the Cancer Centre, The Institute of Maria Skłodowska-Curie, 375 breast ultrasound examinations were conducted. The examined group included patients who in B-mode examinations presented indications for pathological verification. They were 80 women aged between 17 and 83 (mean age was 50) with 99 solid focal lesions in the breasts. All patients underwent: the interview, physical examination, B-mode ultrasound examination and elastography of the mammary glands and axillary fossae. The visualized lesions were evaluated according to BIRADS-US classification and Tsukuba score as well as FLR ratio was calculated. In all cases, the histopathological and/or cytological verification of the tested lesions was obtained. Results: In the group of 80 patients, the examination revealed 39 malignant neoplastic lesions and 60 benign ones. The mean age of women with malignant neoplasms was 55.07 (SD=10.54), and with benign lesions – 46.9 (SD=15.47). In order to identify threshold values that distinguish benign lesions from malignant ones, a comparative analysis of statistical models based on BIRADS-US classification and Tsukuba score was conducted and the cut-off value for FLR was assumed. The sensitivity and specificity values for BIRADS-US 4/5 were 76.92% and 96.67% and for Tsukuba 3/4 – 64.1% and 98.33% respectively. The assumed FLR threshold value to differentiate between benign and malignant lesions in the breasts equaled 3.13. The combined application of both classifications (with the threshold value of BIRADS-US 4/Tsukuba 3) improved the total value of sensitivity and specificity of character differentiation of focal lesions (87.2% and 95% respectively). Conclusions: In the case of problematic focal lesions, i.e. BIRADS-US 3, the study revealed that obtaining Tsukuba score of 1 and 2 for lesions classified as BIRADS-US 3 confirms their benign character. This allows to avoid the cytological verification.Sonoelastografia jest dynamicznie rozwijającą się metodą badania ultrasonograficznego wykorzystywaną w różnicowaniu charakteru zmian ogniskowych w piersiach. Celem II części pracy było określenie przydatności sonoelastografii w diagnostyce różnicowej litych zmian ogniskowych w piersiach, w tym ocena wartości diagnostycznej skali Tsukuba i wskaźnika FLR w różnicowaniu charakteru litych zmian w piersiach oraz ocena porównawcza klasycznego obrazowania B-mode i sonoelastografii. Materiał i metoda: W okresie od stycznia do lipca 2010 roku w Pracowni Ultrasonograficznej Centrum Onkologii – Instytutu im. Marii Skłodowskiej-Curie wykonano 375 badań ultrasonograficznych piersi u kobiet. Do grupy badanej włączono pacjentki, u których na podstawie obrazowania B-mode ustalono wskazania do weryfikacji patologicznej, tj. 80 kobiet w wieku od 17 do 83 lat (średnio 50 lat) z obecnością 99 litych zmian ogniskowych w piersiach. U wszystkich pacjentek wykonano badanie podmiotowe, przedmiotowe oraz badanie ultrasonograficzne B-mode i elastografię gruczołów piersiowych oraz dołów pachowych. Uwidocznione zmiany ogniskowe w piersiach oceniano zgodnie z klasyfikacją BIRADS-usg, skalą Tsukuba oraz obliczano wskaźnik FLR. We wszystkich przypadkach uzyskano weryfikację histopatologiczną i/lub cytologiczną badanych zmian. Wyniki: W grupie 80 badanych kobiet stwierdzono obecność 39 zmian nowotworowych złośliwych oraz 60 o charakterze łagodnym. Średnia wieku kobiet ze zmianami nowotworowymi złośliwymi wynosiła 55,07 roku (SD=10,54), a kobiet, u których rozpoznano zmiany łagodne – 46,9 roku (SD=15,47). W celu identyfikacji wartości progowych różnicujących zmiany łagodne od złośliwych przeprowadzono analizę porównawczą modeli statystycznych opartych na klasyfikacji BIRADS-usg i skali Tsukuba oraz wyznaczono wartość odcięcia dla wskaźnika FLR. Dla klasyfikacji BIRADS-usg 4/5 uzyskano czułość i swoistość odpowiednio 76,92% i 96,67%, a dla skali Tsukuba 3/4 – odpowiednio 64,1% i 98,33%; uzyskana wartość progowa FLR różnicująca zmiany łagodne od złośliwych nowotworów piersi wynosiła 3,13. Łączne zastosowanie obydwu klasyfikacji (z wartością progową BIRADS-usg 4/Tsukuba 3) poprawia sumę czułości i swoistości rozpoznań charakteru zmian ogniskowych (odpowiednio 87,2% i 95%). Wnioski: W przypadku problematycznych zmian ogniskowych, tj. BIRADS-usg 3, wykazano, iż uzyskanie w elastografii stopni Tsukuba 1 i 2 dla zmian BIRADS-usg 3 potwierdza ich łagodny charakter, tym samym pozwala odstąpić od weryfikacji cytologicznej

Quantitative Assessment of the Echogenicity of a Breast Tumor Predicts the Response to Neoadjuvant Chemotherapy

The aim of the study was to improve monitoring the treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Ultrasound examinations were performed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was the standard of reference. Alteration in B-mode ultrasound (tumor echogenicity and volume) and the Kullback-Leibler divergence (kld), as a quantitative measure of amplitude difference, were used. Correlations of these parameters with RMC were assessed and Receiver Operating Characteristic curve (ROC) analysis was performed. Thirty-nine patients (mean age 57 y.) with 50 tumors were included. There was a significant correlation between RMC and changes in quantitative parameters (KLD) after the second, third and fourth course of NAC, and alteration in echogenicity after the third and fourth course. Multivariate analysis of the echogenicity and KLD after the third NAC course revealed a sensitivity of 91%, specificity of 92%, PPV = 77%, NPV = 97%, accuracy = 91%, and AUC of 0.92 for non-responding tumors (RMC ≥ 70%). In conclusion, monitoring the echogenicity and KLD parameters made it possible to accurately predict the treatment response from the second course of NAC