Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

BACKGROUND: Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. METHODS: This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). RESULTS: A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CONCLUSION: CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients.

PURPOSE: The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on (18)F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. METHODS: Data were processed by two nuclear medicine physicians in Reggio Emilia and Créteil. Nineteen phantoms filled with (18)F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm(3) with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41% SUVmax threshold (TMTV41) and a variable visually adjusted SUVmax threshold (TMTVvar). RESULTS: In phantoms, the 41% threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV41 measurement was substantial (ρ c = 0.986, CI 0.97 - 0.99) and the difference between the means was not significant (212 ± 218 cm(3) for Créteil vs. 206 ± 219 cm(3) for Reggio Emilia, P = 0.65). By contrast the agreement was poor for TMTVvar. There was a significant direct correlation between TMTV41 and normalized LDH (r = 0.652, CI 0.42 - 0.8, P <0.001). Higher disease stages and bulky tumour were associated with higher TMTV41, but high TMTV41 could be found in patients with stage 1/2 or nonbulky tumour. CONCLUSION: Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.

Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

Tumour burden at diagnosis as the main clinical predictor of cell resistance in patients with early stage, favourable Hodgkin lymphoma treated with VBM chemotherapy plus radiotherapy.

We verified whether early resistance to treatment can be predicted in a subset of patients with very favourable, early stage Hodgkin lymphoma, treated with VBM (vinblastine, bleomycin and methotrexate) chemotherapy and involved-field radiotherapy, an effective combination with very low early and late toxicity. The relative tumour burden (rTB) was volumetrically measured from the staging computed tomography and analysed together with the parameters of pre-therapy evaluation in 61 patients enrolled into the protocol MH-1b of the Gruppo Italiano Studio Linfomi between 1996 and 2003. Early failure, codified by either less than complete remission (i.e. partial/null response or progression) or early relapse (within 12 months from the end of therapy), was considered as clinical expression of resistance to treatment. Logistic regression and failure-free survival were the statistical tools for the analysis. The rTB demonstrated to be the best predictor of early failure, outperforming every other pre-treatment parameter, International Prognostic Score included. With a mean rTB value of 44.964 ± 34.788 cm(3)/m(2) in the 53 patients successfully treated and of 130.185 ± 63.993 cm(3)/m(2) in the eight with early treatment failure, the risk of resistance showed fivefold and 10-fold increases at rTB of 52.002 and 74.497 cm(3)/m(2), respectively. Only two patients relapsed more than 12 months after the end of therapy; both had a high initial rTB. The rTB is the best predictor of resistance also in the subset of patients with very favourable, early stage disease. Safe rTB limits are proposed for successful administration of VBM chemotherapy plus involved-field radiotherapy.

Tumour burden predicts treatment resistance in patients with early unfavourable or advanced stage Hodgkin lymphoma treated with ABVD and radiotherapy.

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the lesions except bone marrow involvement, which was quantified by calculation. The relationship with early resistance was analysed with logistic regressions. The rTB demonstrated to be the best predictor of early failure in both patient subsets, being superior to the multiparameter International Prognostic Score. The rTB showed a significant exponential relationship with the relative risk of early failure, and with inclusion of the extranodal involvement into the model, a single equation became adequate to predict resistance in both early unfavourable and advanced stage patients. The conclusions are that the rTB is the best pretreatment factor related to the risk of resistance to combined ABVD + radiotherapy and that this relationship can be mathematically expressed in an easy way. A simplified assessment of rTB is highly desirable.

Tumor burden in Hodgkin's lymphoma can be reliably estimated from a few staging parameters.

The relative tumor burden (rTB), the tumor burden normalized to body surface area, is of prime clinical and prognostic value in Hodgkin's lymphoma. However, its measurement is rather complicated and a bedside computation cannot be proposed. We investigated the possibility of estimating, instead of measuring, rTB from elementary parameters of the initial staging. The rTB of 507 patients, treated with therapeutic protocols of the Gruppo Italiano Studio Linfomi according to their staging characteristics, was measured through their pre-therapy computed tomographies. The relationships between rTB and staging characteristics were analyzed with simple and multiple regressions both in a training sample (254 patients) for a selection of predictive parameters, and in a test sample (253 patients) for validation of the results. The number of involved sites, bulky mass and the IPI score were the variables best related to rTB. The resulting final equation {estimated rTB=-4.3+8.3xIPI2+22.7x[no. of involved sites (+3 if a bulky mass is present)]} provided the maximal approximation to the measured rTB (R2=0.671). The validity of the equation was confirmed on the test sample and the predictive superiority of the estimated rTB over IPI was still evident in terms of failure-free survival in both groups of patients. The estimated rTB is accurate enough to retain most of the prognostic advantage of the measured rTB over the IPI score. It can be easily calculated, allows a valid approximation of the measured rTB, and can be proposed as a useful tool for clinical research and practice.

Chemoresistance as a function of the pretherapy tumor burden and the chemotherapy regimen administered: differences observed with 2 current chemotherapy regimens for advanced Hodgkin lymphoma.

BACKGROUND: The mature results from trials comparing ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) and BEACOPP (bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, Oncovin [vincristine], procarbazine, prednisone) chemotherapies in advanced Hodgkin lymphoma will be available in some years. An early comparison of their curative potential can however be obtained from an assessment of initial tumor burden and chemoresistance. PATIENTS AND METHODS: Less than a complete remission after treatment and relapse occurring within 12 months thereafter were assumed to be clinical expressions of chemoresistance. The tumor burden was calculated from the measurements of all the lesions documented by staging computed tomography (CT) and was normalized to body surface area to give the relative tumor burden (rTB). Using logistic regression analysis, the relationship between initial rTB, chemoresistance, and chemotherapy regimen administered was retrospectively studied in 222 patients selected from those enrolled in 2 similar randomized trials. RESULTS: The median rTB volumes were 157.9 cm(3)/m(2) in the 115 patients treated with ABVD vs. 154.6 cm(3)/m(2) in the 107 patients treated with BEACOPP, and the distribution of the volumes was identical in the 2 groups. The rTB was confirmed as the best predictor of early treatment failures (22 less than complete responses plus 21 early relapses). For the same rTB, the risk of chemoresistance to BEACOPP was about half that of the chemoresistance to ABVD or, for a given risk of chemoresistance, BEACOPP cured patients with an rTB 89.1 cm(3)/m(2) greater than that cured by ABVD (ie, more than 50% of the median tumor load of patients with advanced-stage disease). CONCLUSION: This account of rTB allows an early comparative evaluation of the curative ability of different chemotherapy regimens.