Computer-aided diagnosis system for characterizing ISUP grade≥2 prostate cancers at multiparametric MRI: A cross-vendor evaluation.

PURPOSE: To assess the performance of a computer-aided diagnosis (CADx) system trained at characterizing International Society of Urological Pathology (ISUP) grade≥2 peripheral zone (PZ) prostate cancers on multiparametric magnetic resonance imaging (mpMRI) examinations from a different institution and acquired on different scanners than those used for the training database. PATIENTS AND METHODS: Preoperative mpMRIs of 74 men (median age, 65.7 years) treated by prostatectomy between 2014 and 2017 were retrospectively selected. One radiologist outlined suspicious lesions and scored them using Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2); their CADx score was calculated using a classifier trained on an independent database of 106 patients treated by prostatectomy in another institution. The lesions' nature was assessed by comparison with prostatectomy whole-mounts. Diagnostic accuracy was estimated with areas under receiver operating characteristic curves (AUCs). Sensitivity and specificity were calculated using a CADx threshold (≥0.21) that yielded 95% sensitivity in the training database, and a PI-RADSv2≥3 threshold. RESULTS: A total of 127 lesions (PZ, n=104; transition zone [TZ], n=23) were described. In PZ, CADx and PI-RADSv2 scores had similar AUCs for characterizing ISUP grade≥2 cancers (0.78 [95% confidence interval (CI): 0.69-0.87] vs. 0.74 [95%CI: 0.62-0.82], respectively) (P=0.59). Sensitivity and specificity were respectively 89% (95%CI: 82-97%) and 42% (95%CI: 26-58%) for the CADx score, and 97% (95%CI: 93-100%) and 37% (95%CI: 22-52%) for the PI-RADSv2 score. In TZ, both scores showed poor specificity. CONCLUSION: In this external cohort, the CADx and PI-RADSv2 scores showed similar performances in characterizing ISUP grade≥2 cancers.

DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences.

OBJECTIVE: To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. METHODS: A comprehensive survey of the literature using the search phrases "locoregional breast cancer recurrence", "chest wall recurrence", "local recurrence", "regional recurrence", and "breast cancer" was performed, using the limits "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guidelines". CONCLUSIONS: Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts depend on the time interval to first radiotherapy, presence of late radiation effects, and concurrent or sequential systemic treatment. Combination with hyperthermia can further improve tumor control. In patients with isolated axillary or supraclavicular recurrence, durable disease control is best achieved with multimodality therapy including surgery and radiotherapy. Radiation therapy significantly improves local control and should be applied whenever feasible.

Characterization of prostate cancer using T2 mapping at 3T: a multi-scanner study.

RATIONALE AND OBJECTIVES: To assess the prostate T2 value as a predictor of malignancy on two different 3T scanners. PATIENTS AND METHODS: Eighty-three pre-prostatectomy multiparametric MRIs were retrospectively evaluated [67 obtained on a General Electric MRI (scanner 1) and 16 on a Philips MRI (scanner 2)]. After correlation with prostatectomy specimens, readers measured the T2 value of regions-of-interest categorized as "cancers", "false positive lesions", or "normal tissue". RESULTS: On scanner 1, in PZ, cancers had significantly lower T2 values than false positive lesions (P=0.02) and normal tissue (P=2×10(-9)). Gleason≥6 cancers had similar T2 values than false positive lesions and significantly higher T2 values than Gleason≥7 cancers (P=0.009). T2 values corresponding to a 25% and 75% risk of Gleason≥7 malignancy were respectively 132 ms (95% CI: 129-135 ms) and 77 ms (95% CI: 74-81 ms). In TZ, cancers had significantly lower T2 values than normal tissue (P=0.008), but not than false positive findings. Mean T2 values measured on scanner 2 were not significantly different than those measured on scanner 1 for all tissue classes. CONCLUSION: All tested tissue classes had similar mean T2 values on both scanners. In PZ, the T2 value was a significant predictor of Gleason≥7 cancers.

Imaging of shear waves induced by Lorentz force in soft tissues.

This study presents the first observation of elastic shear waves generated in soft solids using a dynamic electromagnetic field. The first and second experiments of this study showed that Lorentz force can induce a displacement in a soft phantom and that this displacement was detectable by an ultrasound scanner using speckle-tracking algorithms. For a 100 mT magnetic field and a 10 ms, 100 mA peak-to-peak electrical burst, the displacement reached a magnitude of 1 µm. In the third experiment, we showed that Lorentz force can induce shear waves in a phantom. A physical model using electromagnetic and elasticity equations was proposed. Computer simulations were in good agreement with experimental results. The shear waves induced by Lorentz force were used in the last experiment to estimate the elasticity of a swine liver sample.

DEGRO practical guidelines: radiotherapy of breast cancer III--radiotherapy of the lymphatic pathways.

AIM: The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). METHODS: A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: "breast cancer", "radiotherapy", "regional node irradiation". Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. RESULTS: International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. CONCLUSION: Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk-benefit relationship appears to shift towards an improvement of outcome.

DEGRO practical guidelines: radiotherapy of breast cancer II: radiotherapy of non-invasive neoplasia of the breast.

PURPOSE: To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. METHODS: The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were "non invasive breast cancer", "ductal carcinoma in situ, "dcis", "borderline breast lesions", "lobular neoplasia", "radiotherapy" and "radiation therapy". In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. RESULTS: Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50 % of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose-volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing. CONCLUSION: Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets-even in low risk subgroups (LoE 1a).

DEGRO practical guidelines: radiotherapy of breast cancer I: radiotherapy following breast conserving therapy for invasive breast cancer.

BACKGROUND AND PURPOSE: The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012. METHODS: A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms "breast cancer", "radiotherapy", and "breast conserving therapy". Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer. RESULTS: Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48-0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75-0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified. CONCLUSION: After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.

BACKGROUND: The treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. PATIENTS AND METHODS: Two hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18-20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. RESULTS: Numbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. CONCLUSIONS: Local radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.

When are breast cancer patients old enough for the quitclaim of local control?

BACKGROUND: Although postoperative radiotherapy (RT) after breast-conserving surgery (BCS) halves the 10-year recurrence rate in breast cancer patients through all age groups, the question of whether RT may be omitted and replaced by endocrine therapy for women aged 70 years and older with low-risk factors has recently become an issue of debate. METHODS: Survey of the relevant recent literature (Medline) and international guidelines. RESULTS: Three randomized studies investigating the effect of RT in older women revealed significantly increased local recurrence rates when RT was omitted, and a negative impact on disease-free survival was observed in two of these trials. Despite these findings, in one of the studies omission of RT in women over 70 is recommended, leading to a respective amendment in the guidelines of the American National Comprehensive Cancer Network. Several large retrospective cohort studies analyzing the outcome of patients over 65 years with and without RT have since been published and showed a significantly improved local control in all subgroups of advanced age and stage, which predominantly translated into improved disease-free and overall survival. CONCLUSION: No subgroup of elderly patients has yet been identified that did not profit from RT in terms of local control. Therefore, chronological age alone is not an appropriate criterion for deciding against or in favor of adjuvant RT. The DEGRO breast cancer expert panel explicitly discourages determination of a certain age for the omission of postoperative RT in healthy elderly women with low-risk breast cancer. For frail elderly women, treatment decisions should be individually decided on the basis of standardized geriatric assessment.

Visualisation of liver tumours using hand-held real-time strain imaging: results of animal experiments.

OBJECTIVE: Surgical resection is the only curative option for colorectal hepatic metastases. Intra-operative localisation of these metastases during hepatic resection is performed by intra-operative B-mode imaging and palpation. Because liver metastases are stiffer than normal tissues, elastography may be a useful complement to B-mode imaging. This paper reports quantitative measures of the image quality attained during intra-operative real-time elastographic visualisation of liver metastasis. METHODS: VX2 tumours were implanted in the liver of eight rabbits and were scanned in vivo. Measurements of the tumour dimensions obtained via elastography were compared with those obtained using B-mode imaging and with gross pathology. RESULTS: Measurements of tumour diameters were similar when obtained by intra-operative elastography and pathological measurement methods (mean difference±standard deviation, 0.1±0.9 mm). The contrast between tumours and normal tissues was significantly higher (p<0.05) in elastograms (26±10 dB contrast) than in sonograms (1±1 dB contrast). Sensitivity and specificity for detecting tumours using intra-operative elastography were 100% and 88%, respectively, and positive and negative predictive values were 89% and 100%, respectively. In two cases elastograms were able to detect a tumour that was ambiguous in B-mode images. CONCLUSION: Combined hand-held B-mode/strain imaging may provide additional information that is relevant for detection of liver metastases that may be missed by standard B-mode imaging alone, such as small and/or isoechoic tumours.

[Follow-up of testicular germ cell cancer patients: interdisciplinary evidence-based recommendations]. / Nachsorge von Patienten mit Hodentumoren : Interdisziplinäre evidenzbasierte Empfehlungen.

BACKGROUND: Clear treatment recommendations for patients with testicular cancer exist and their stringent application has led to significant improvements in remission and survival rates. Moreover, active surveillance has become a cornerstone in the management of clinical stage I seminomatous and nonseminomatous germ cell tumors. On the other hand, the existing recommendations for the follow-up of testis cancer patients differ widely and have been changed frequently in recent years. MATERIAL AND METHODS: Follow-up recommendations in this young patient population have to be as evidence-based as possible, feasible in order to ensure adherence, and should not be harmful. Primarily, attention has to be paid to the negative impact of unnecessary radiation exposure. RESULTS: Recently, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging at follow-up, and the risks of excessive radiation due to imaging, in particular that of CT scans. An interdisciplinary multinational working group consisting of urologists, medical oncologists, and radiation oncologists has reviewed and discussed the current evidence and on this basis formulated new recommendations for patients with germ cell tumors of the testis.

[A multi-disciplinary approach to the treatment of germ cell tumors]. / Multimodale Therapiekonzepte von Keimzelltumoren.

The management of patients with germ cell tumors must be based upon complete staging and should be risk-adapted. Seminoma stage I can be managed by either active surveillance, adjuvant carboplatin therapy, or radiotherapy. Seminoma stage IIA should receive radiotherapy, stage IIB can be managed with either radiotherapy or chemotherapy. Seminoma stage IIC and III are treated with three (to four) cycles of PEB (cisplatin, etoposide, bleomycin). Nonseminoma stage I should be managed by either active surveillance or adjuvant chemotherapy with one (to two) cycles of PEB, based upon the risk factor vascular invasion. Treatment of advanced nonseminoma consists of either 3 or 4 cycles of PEB and must be guided by the IGCCCG prognostic subgroup. Prognosis is particularly poor in patients with either primary mediastinal nonseminoma, and/or metastases to liver, brain or bone, or inadequate tumor marker decline. In these cases, intensification of therapy with high dose chemotherapy can be justified. Complex cases with poor prognosis and all patients with relapsed disease should exclusively be treated by experts in a tertiary care setting to achieve highest possible cure rates in these young patients.

Actual management of ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) represents a premalignant, non-invasive intraductal carcinoma of the breast. About 30% of all mammographically detected breast cancers contain DCIS. Due to the increased use of mammography during the last 20 years the incidence of DCIS has dramatically risen. Histologically it represents a heterogenous group of potentially malignant lesions. The prognosis of DCIS is excellent, but the optimal management of the disease still remains controversial. This review summarizes the results of the latest randomized trials and retrospective analyses investigating the optimal therapeutic strategies in the treatment of DCIS. In addition, it presents a range of treatment options on the basis of the guidelines of the German gynecological oncology group (AGO) 2008.