The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study

To assess the benefit of intraventricular chemotherapy, patients with leptomeningeal metastasis (LM) from breast cancer were randomised to treatment including intraventricular (IT) chemotherapy (n = 17) or to non-intrathecal (non-IT) treatment (n = 18). Appropriate systemic therapy and involved field radiation therapy (RT) were given in both arms. Intention-to-treat analysis showed neurological improvement or stabilisation in 59% of the IT and in 67% of the non-IT group, with median time to progression of 23 weeks (IT) and 24 weeks (non-IT). Median survival of IT patients was 18.3 weeks and 30.3 weeks for non-IT patients (difference 12.9 weeks; 95% Confidence Interval (CI) −5.5 to +34.3 weeks; P = 0.32). Neurological complications of treatment occurred in 47% (IT) vs 6% (non-IT) (P = 0.0072). In conclusion, standard systemic chemotherapy with involved field RT for LM from breast cancer is feasible. Addition of intraventricular chemotherapy does not lead to survival benefit or improved neurological response, and is associated with an increased risk of neurotoxicity.     

Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer

BackgroundThe aim of this study was to evaluate the accuracy of clinical imaging of the primary breast tumour post-neoadjuvant chemotherapy (NAC) related to the post-neoadjuvant histological tumour size (gold standard) and whether this varies with breast cancer subtype. In this study, results of both magnetic resonance imaging (MRI) and ultrasound (US) were reported.MethodsPatients with invasive breast cancer were enrolled in the INTENS study between 2006 and 2009. We included 182 patients, of whom data were available for post-NAC MRI (n = 155), US (n = 123), and histopathological tumour size.ResultsMRI estimated residual tumour size with <10-mm discordance in 54% of patients, overestimated size in 28% and underestimated size in 18% of patients. With US, this was 63%, 20% and 17%, respectively. The negative predictive value in hormone receptor-positive tumours for both MRI and US was low, 26% and 33%, respectively. The median deviation in clinical tumour size as percentage of pathological tumour was 63% (P₂₅ = 26, P₇₅ = 100) and 49% (P₂₅ = 22, P₇₅ = 100) for MRI and US, respectively (P = 0.06).ConclusionsIn this study, US was at least as good as breast MRI in providing information on residual tumour size post-neoadjuvant chemotherapy. However, both modalities suffered from a substantial percentage of over- and underestimation of tumour size and in addition both showed a low negative predictive value of pathologic complete remission (Gov nr: NCT00314977).     

Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: A systematic review

Background

Axillary metastatic lymphadenopathy with no primary tumour identified in the breast on physical examination, mammography or ultrasound is referred to as occult breast cancer. The goal of this systematic review is to give an overview of the value and additional considerations of using breast MRI in occult breast cancer.

Methods

The databases of Pubmed, Embase, CINAHL and the Cochrane library were searched for studies addressing the use of breast MRI in occult breast cancer. Cross-referencing was used to find additional articles.

Results

8 retrospective studies were included. Breast MRI can detect an otherwise occult breast cancer in more than two thirds of patients with a high sensitivity but lower specificity. In 80% of patients MRI detected lesions could be localized again by using ultrasound. Furthermore the size and localization of the lesions found on MRI most often correlated closely with findings at pathology. Breast MRI also provided the possibility of breast conserving surgery in one thirds of patients.

Conclusion

Breast MRI can result in additional detection of otherwise occult lesions in occult breast cancer. Because of low specificity of malignant lesion detection by breast MRI, lesions should be histologically confirmed. This can be achieved either by MRI or ultrasound guided biopsy, as long as all MRI detected lesions are histologically checked. Routine application of breast MRI in occult breast cancer may also alter locoregional treatment by offering the possibility of breast conserving surgery in one thirds of patients.     

High dose chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis

BACKGROUND: High dose chemotherapy with autologous transplantation of bone marrow or peripheral stem cells (autograft) has been considered promising for treating poor prognosis breast cancer. We reviewed the relevant evidence. METHODS: We included randomised controlled trials comparing high dose chemotherapy and autograft with conventional chemotherapy for women with early poor prognosis breast cancer. We searched medical databases (Cochrane Library, MEDLINE, EMBASE), websites (co-operative cancer research groups, American Society of Clinical Oncologists) and citations of articles found, to September 2006. Where appropriate, data were pooled to obtain a relative risk, using a fixed effects model. Clinical, methodological and statistical heterogeneity were examined with sensitivity analyses. FINDINGS: Thirteen trials with 5064 women were included. There was a significant benefit in event-free survival for the high dose group at three years (RR 1.19 (95% CI 1.06, 1.19)) and four years (RR 1.24 (95% CI 1.03, 1.50)) and at five years this benefit approached statistical significance (RR 1.06 (95% CI 1.00, 1.13)). Overall survival rates were not significantly different at any stage of follow up. There were significantly more treatment-related deaths on the high dose arm (RR 8.58 (95% CI 4.13, 17.80)). Morbidity was higher in the high dose group but there was no significant difference in the incidence of second cancers. The high dose group reported significantly worse quality of life immediately after treatment, but there were few differences by one year. INTERPRETATION: There is insufficient evidence supporting routine use of high dose chemotherapy with autograft for treating early poor prognosis breast cancer.     

Optimal timing of surgery following breast cancer neoadjuvant chemotherapy: A systematic review and meta-analysis

BackgroundAdministration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT).MethodsThe primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between <4 weeks and 4–8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method.ResultsFive studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34–0.65) and DFS(OR 0.71 (95% c. i 0.52–0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46–1.33, P = 0.37). There was no difference in pCR rate between those that had surgery <4 weeks and 4–8 weeks (OR 1.01, 95% c. i 0.80–1.28, P = 0.93).ConclusionThis meta-analysis shows that the optimum timing of surgery post completion of NACT is 4–8 weeks as it is associated with increased OS and DFS.     

Contrast enhanced magnetic resonance imaging underestimates residual disease following neoadjuvant docetaxel based chemotherapy for breast cancer

AIMS: We prospectively compared the ability of magnetic resonance imaging (MRI) to measure residual breast cancer in patients treated with different neoadjuvant chemotherapy regimen. METHODS: Forty patients with locally advanced breast carcinoma underwent neoadjuvant chemotherapy. Twelve patients received 5-fluoro-uracyl-epirubicin-cyclophosphamide (FEC-group, six cycles), 28 (DXL-group) received docetaxel-based chemotherapy (six cycles DXL-epirubicin: 13 patients, eight cycles DXL alone: 15 patients). All patients had baseline and preoperative MRI. The spread of pathologic residual disease (PRd) was compared to preoperative MRI measures according to chemotherapy regimen. RESULTS: MRI over/underestimation of the spread of residual tumour was never superior to 15mm in FEC group, whereas it appeared in 11/28 (39%, 30-48%-95% CI) patients in DXL group (p=0.017). Tumour shrinkage led to single nodular residual lesions in FEC group, whereas vast numerous microscopic nests were observed in docetaxel group in pathology. CONCLUSION: Among tumours treated with a taxane-containing regimen, residual disease was frequently underestimated by MRI because of PRd features.     

影像学预测乳腺癌患者预后及新辅助化疗反应的研究进展

在世界范围内,乳腺癌是女性发病率最高的恶性肿瘤,也是女性因癌症死亡的主要原因。新辅助化疗(Neoadjuvant chemotherapy,NAC)可以降低乳腺癌分期、缩小肿瘤,甚至使病灶达到病理完全缓解(Pathological complete response,pCR),在乳腺癌综合治疗中得到广泛应用。由于患者对治疗的反应各有差异,所以及时准确评估NAC疗效已成为临床医生关注并致力解决的重点。常规影像学检查手段如乳腺钼靶、超声、PET-CT和磁共振成像(MRI)已广泛用于乳腺癌NAC疗效的评估,且每种影像学检查各有优势和不足。本文就常规影像学检查用于预测乳腺癌患者预后及NAC疗效的研究进展进行综述。     

乳腺磁共振在乳腺癌诊断治疗中的运用

乳腺MRI具有很好的软组织分辨率和无射线辐射等优点,对乳腺癌的早期诊断和局部分期明显优于乳腺X线摄影和超声检查。随着乳腺癌个体化、规范化综合治疗理念的推广,乳腺MRI在综合治疗中的作用日益受到重视,伴随对乳腺MRI临床应用的开展和研究的深入,其在乳腺癌分期中的评估、保乳手术病例术前的筛选、腋窝淋巴结转移原发不明者的诊断、新辅助化疗(neoadjuvant chemotherapy, NAC)的疗效评估、随访监测中的应用价值也得到了很好的评估。同时,乳腺MRI对肿瘤范围的客观准确的评估也是正确选择治疗方式的依据。     

The role of neoadjuvant chemotherapy for breast cancer treatment

Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.     

Magnetic resonance imaging in patients with newly diagnosed breast cancer: A review of the literature

The use of magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer remains controversial. Here we review the current use of breast MRI and the impact of MRI on short‐term surgical outcomes and rates of local recurrence. In addition, we address the use of MRI in specific patient populations, such as those with ductal carcinoma in situ, invasive lobular carcinoma, and occult primary breast cancer, and discuss the potential role of MRI for assessing response to neoadjuvant chemotherapy. Although MRI has improved sensitivity compared with conventional imaging, this has not translated into improved short‐term surgical outcomes or long‐term patient benefit, such as improved local control or survival, in any patient population. MRI is an important diagnostic test in the evaluation of patients presenting with occult primary breast cancer and has shown promise in monitoring response to neoadjuvant chemotherapy; however, the data do not support the routine use of perioperative MRI in patients with newly diagnosed breast cancer. Cancer 2014;120:120:2080–2089. © 2014 American Cancer Society.     

Successful treatment of leptomeningeal metastases from breast cancer using the combination of trastuzumab and capecitabine: a case report

We report a case of metastatic breast cancer with leptomeninges and multiple bone metastases that showed an excellent response to the combination of trastuzumab and capecitabine; therapeutic effect was evaluated by MRI at follow-up. A 44-year-old woman underwent modified radical mastectomy in February 1997. In April 2003, a tumor at the right basis cerebri and multiple bone metastases were noted, and in October 2003, she underwent enucleation of the tumor. Histopathologically, the tumor was consistent with a basal skull metastasis from breast cancer. In March 2004, the patient began to experience pain, weakness, and paresthesia of both legs. She was diagnosed, with leptomeningeal metastasis (LM) from breast cancer using MRI. In December 2005, the combination of trastuzumab and capecitabine administered as sixth-line treatment was very effective for LM. Although it is generally very difficult to diagnose LM and assess the therapeutic effect with MRI, in this case, it was possible. To our knowledge, there has been no report in the literature describing the combination of trastuzumab and capecitabine for LM from breast cancer. Although the mechanism underlying the efficacy of this combination is still unknown, the treatment would be worth trying because of its few side effects in extensively treated patients with LM from breast cancer. To confirm the antitumor efficacy of trastuzumab and capecitabine, however, further investigations are required.     

Accuracy of MRI for treatment response assessment after taxane- and anthracycline-based neoadjuvant chemotherapy in HER2-negative breast cancer

Background

Studies suggest that MRI is an accurate means for assessing tumor size after neoadjuvant chemotherapy (NAC). However, accuracy might be dependent on the receptor status of tumors. MRI accuracy for response assessment after homogenous NAC in a relative large group of patients with stage II/III HER2-negative breast cancer has not been reported before.

Methods

250 patients from 26 hospitals received NAC (docetaxel, adriamycin and cyclophosphamide) in the context of the NEOZOTAC trial. MRI was done after 3 cycles and post-NAC. Imaging (RECIST 1.1) and pathological (Miller and Payne) responses were recorded. Accuracy measures were calculated and MRI and pathologically assessed tumor sizes were correlated. Tumor size over- and underestimation were quantified.

Results

Accuracy of MRI for determining pathological complete response (pCR) was 76%. The ROC-curve of MRI response and pCR had an area under the curve value of 0.63 (95% C.I. 0.52–0.74). The correlation coefficient of MRI and histopathological tumor measurements was 0.46 (p < 0.001). Correlations were different for ER-positive (r = 0.40, p < 0.001) and ER-negative (r = 0.76, p < 0.001) breast tumors. MRI under- and overestimated the tumor size in 47% and 40% of all patients. In cases of substantial tumor size underestimation (>2 cm), surgical margins were more often tumor positive compared to the rest of the patients (33% vs.12%, p = 0.005).

Conclusion

MRI measurements correlated moderately with tumor size on the surgical specimen. Only in ER-negative breast tumors, MRI tumor sizes correlated sufficiently with residual tumor size on the pathological specimen. Therefore, post-NAC MRI should be interpreted with caution.     

Intrathecal administration of anti-HER2 treatment for the treatment of meningeal carcinomatosis in breast cancer: A metanalysis with meta-regression

Leptomeningeal Metastases (LM) is a turning point in terms of prognosis and quality of life of patients with breast cancer (BC). Intrathecal therapy is largely used for the treatment of breast cancer LM. In this metanalysis with meta-regression, we gathered data on intrathecal (IT) trastuzumab administration in patients with HER2 positive breast cancer with LM. A total of 24 articles (58 patients) were included in the study and intrathecal trastuzumab was used in all patients. The mean age at IT administration was 50.7 years (SD 11.4, range 24–80) and the mean total dose of IT trastuzumab was 711.9 mg (SD 634.9, median 450). IT trastuzumab was used both alone (n = 20) and in combination with systemic pharmacotherapy (n = 37). No serious adverse events were reported in 87.9% of cases. In this selected population a significant clinical improvement was observed in 55.0% of cases while stabilization was reported in 14% of cases. CSF response was observed in 55.6% of the cases. MRI was improved or stable in 70.8% of the cases. Interestingly, the CNS-PFS was 5.2 months and the median OS was 13.2 months. A clinical improvement (HR 0.13, 95% CI 0.03–0.49) and CSF response (HR 0.13, 95% CI 0.03–0.58) were associated with a longer CNS-PFS. The association of longer CNS-PFS with radio- or neurosurgery prior to the administration of IT trastuzumab did not reach statistical significance. This metanalysis with meta-regression indicates that IT trastuzumab in patients with HER2 positive breast cancer LM might be a safe and effective treatment, but further prospective studies are needed to definitively prove such a point.     

定量动态增强磁共振评估乳腺癌新辅助化疗疗效的应用研究

背景与目的：乳腺癌的新辅助化疗(neoadjuvant chemotherapy, NAC)已成为成熟的治疗方法,但疗效评估尚未有统一有效的方法。该研究即探讨定量动态增强磁共振在乳腺癌NAC疗效评估中的价值。方法：24例术前行NAC的乳腺癌确诊患者(24例均为浸润性导管癌),分别于NAC前、第2个疗程后、化疗结束但术前3个时间点行定量动态增强磁共振检查,分析NAC前后肿瘤最长径及动态增强磁共振定量参数：容量转移常数(Ktrans)、速率常数(Kep)、血管外细胞外间隙容积比(Ve)的变化。结果：24例患者均为单侧单发乳腺癌病灶,以RECIST标准分为有效组(17个)和无效组(7个),有效组与无效组Ktrans、Kep在NAC前与第2个疗程、化疗前与化疗结束差异均有统计学意义(P<0.05),Ve在有效组与无效组治疗前后差异均无统计学意义(P>0.05)。结论：定量动态增强磁共振可用来评估NAC疗效,并且Ktrans、Kep可做到定量,使评估结果更为客观真实,但Ve对判断治疗效果未见明显优势。     

Patients’ preferences for surgical and adjuvant systemic treatment in early breast cancer: A systematic review

Purpose

Treatment decisions in early breast cancer can revolve around type of surgery and whether or not to have adjuvant systemic therapy. This systematic review aims to give an overview of patient self-reported factors affecting preferences for breast conserving surgery (BCS) versus mastectomy (MAST), the minimal benefit patients require from adjuvant chemotherapy (aCT) and/or adjuvant hormonal therapy (aHT) to consider it worthwhile, and factors influencing this minimally-required benefit.

Methods

PubMed and EMBASE were searched for relevant articles. Two reviewers independently selected articles and extracted data.

Results

We identified 15 studies on surgical and six on adjuvant systemic treatment decision-making. Factors affecting patient preference for BCS most frequently related to body image (44%), while factors influencing preference for MAST most often related to survival/recurrence (46%). To make adjuvant systemic therapy worthwhile, the median required absolute increase in survival rate was 0.1–10% and the median required additional life expectancy was 1 day to 5 years. The range of individual preferences was wide within studies. Participants in the aHT studies required larger median benefits than those in the aCT studies. Factors associated with judging smaller benefits sufficient most often (44%) related to quality of life (e.g., less treatment toxicity).

Conclusion

Decisive factors in patients’ preferences for surgery type commonly relate to body image and survival/recurrence. Most participants judged small to moderate benefits sufficient to consider adjuvant systemic therapy worthwhile, but individual preferences varied widely. Clinicians should therefore consider the patient’s preferences to tailor their treatment recommendations accordingly.     

MRI弥散加权成像对宫颈癌新辅助化疗评估的应用价值

目的 探讨磁共振扩散加权成像(DWI)对宫颈癌新辅助化疗疗效的评估价值。方法 收集我院经病理证实的31例宫颈癌患者,均于新辅助化疗前后行常规MRI及DWI检查,评估化疗前后肿瘤的DWI图像及其ADC值的变化。结果 治疗前肿瘤最大横径(37.10±11.23)与治疗前ADC值(0.83±0.12)之间的相关关系没有统计学意义(r=-0.175,P=0.348);治疗后肿瘤最大横径(24.03±5.65)与治疗后ADC值(1.10±0.16)之间的相关性没有统计学意义(r=-0.208,P=0.262);治疗前后肿瘤横径缩小程度与ADC增加之间相关性具有统计学意义(r=0.419,P=0.019);化疗有效组20例,无效组11例,有效组治疗后ADC值(0.95±0.13)较治疗前ADC值(0.80±0.12)明显升高,其变化具有统计学意义(P＜0.05),而无效组治疗前ADC值(0.88±0.10)与治疗后ADC值(0.95±0.13)差异无统计学意义(P＞0.05)。结论 DWI序列有助于早期预测和评估宫颈癌新辅助化疗疗效。     

Impact of neoadjuvant chemotherapy on surgical complications in breast cancer: A systematic review and meta-analysis

BackgroundThe increased use of neoadjuvant chemotherapy (NACT) facilitates an increase in breast-conserving surgery and immediate breast reconstruction. While NACT is considered to have the same oncological safety as adjuvant chemotherapy, evidence on the impact of NACT on surgical outcomes following breast surgery is unclear and varies across studies. The aim of this systematic review and meta-analysis was to assess the impact of NACT on surgical complications in breast cancer patients undergoing any kind of breast surgery.MethodsDatabase searches were conducted (March 26, 2021) to identify studies assessing the impact of NACT on postoperative complications. Studies were included if they compared a group of patients treated with NACT to a control group that was not, and if they reported at least one of our defined outcomes. Primary effect measures were odds ratios (ORs) and mean difference with a 95% confidence interval. Study quality was assessed by the Newcastle-Ottawa Scale.ResultsTwenty-six studies comprising 134,191 patients were included. NACT was not associated with an increased complication rate for overall complications (OR: 1.13, 95% CI: 0.86 to 1.47, p = 0.38), individual postoperative complications, nor surgery duration. There was a non-significant trend towards NACT increasing the risk of seroma, wound complications, skin or nipple necrosis, flap ischemia or loss, and implant loss. A significant difference in blood loss was found, favouring NACT (MD = ?75.85, 95% CI: -107.47 to ?44.23, p < 0.00001). Heterogeneity was significant between the studies (I²>50%).ConclusionCompared to a control group, NACT was not found to affect the surgical complications adversely.     

乳腺MRI图像纹理分析在乳腺癌中的研究进展

乳腺癌具有高度异质性,其异质性是造成患者误诊率较高、治疗反应较差及预后不理想等方面的主要原因。纹理分析通过提取不同序列图像纹理特征来评价瘤体及其周围基质的异质性,并将结果与临床、组织病理学和基因组信息相结合,让其能无创地对乳腺病变进行前瞻性评估和预测。随着医学成像领域的高速发展,纹理分析技术不断进步,能够更准确地判断乳腺病变的性质及预后,为临床精准治疗提供更多的信息。本文就纹理分析在鉴别乳腺肿瘤良恶性、预测乳腺癌分子亚型及评估乳腺肿瘤新辅助化疗疗效等方面展开综述。     

节拍化疗在乳腺癌治疗中的应用

节拍化疗是近年来兴起的一种全新的化疗模式,是利用低剂量、多次不间断给药的方式,通过持续抑制肿瘤新生血管生成,达到缩小肿瘤体积、控制肿瘤生长、减少相关药物的不良反应、提高相关疗效、减少相关药物耐药性的作用.目前,在转移性乳腺癌患者的临床治疗中已经取得了肯定的治疗效果.随着治疗模式的改变、概念的不断更新以及越来越多的相关治疗机制被发现,目前节拍式治疗已经不仅是节拍化疗,而是贯穿化疗、放疗、内分泌治疗及相关辅助治疗的治疗模式.本文就节拍化疗在乳腺癌治疗中的应用作一综述.     

Reliability of MRI tumor size measurements for minimal invasive treatment selection in small breast cancers

IntroductionDue to the shift towards minimal invasive treatment, accurate tumor size estimation is essential for small breast cancers. The purpose of this study was to determine the reliability of MRI-based tumor size measurements with respect to clinical, histological and radiomics characteristics in small invasive or in situ carcinomas of the breast to select patients for minimal invasive therapy.Materials and methodsAll consecutive cases of cT1 invasive breast carcinomas that underwent pre-operative MRI, treated in two hospitals between 2005 and 2016, were identified retrospectively from the Dutch cancer registry and cross-correlated with local databases. Concordance between MRI-based measurements and final pathological size was analyzed. The influence of clinical, histological and radiomics characteristics on the accuracy of MRI size measurements were analyzed.ResultsAnalysis included 343 cT1 breast carcinomas in 336 patients (mean age, 55 years; range, 25–81 years). Overall correlation of MRI measurements with pathology was moderately strong (ρ = 0.530, P < 0.001), in 42 cases (12.2%) MRI underestimated the size with more than 5 mm. Underestimation occurs more often in grade 2 and grade 3 disease than in low grade invasive cancers. In DCIS the frequency of underestimation is higher than in invasive breast cancer. Unfortunately, none of the patient, imaging or biopsy characteristics appeared predictive for underestimation.ConclusionSize measurements of small breast cancers on breast MRI are within 5 mm of pathological size in 88% of patients. Nevertheless, underestimation cannot be adequately predicted, particularly for grade 2 and grade 3 tumors, which may hinder patient selection for minimal invasive therapy.