Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually ...treated with the same strategy used for the other types of invasive breast cancer. Anthracycline‐ and taxane‐based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small‐cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast.
Implications for Practice:
Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.
摘要
乳腺神经内分泌癌被认为是罕见疾病, 因此其最佳治疗缺乏相关的前瞻性临床试验数据。对于早期肿瘤, 常采用与其他类型的浸润性乳腺癌相同的治疗策略。以蒽环类和紫杉烷类为基础的方案是新辅助治疗和辅助治疗最常用的方案, 对于转移性肿瘤也是如此; 但在针对小细胞组织学和高增殖指数肿瘤进行治疗时, 已广泛使用联合铂类化合物和依托泊甙的方案。对于转移性疾病, 应基于个体化治疗原则考虑采用多学科治疗策略, 包括化疗、内分泌治疗、多肽受体放射性核素治疗、放射治疗、手术或联合使用以上方案。在不久的将来, 更深入地了解这些肿瘤的生物学将有望为个体化治疗提供更多治疗靶点。我们在本综述中讨论了乳腺神经内分泌癌诊断和治疗的现有证据和未来展望。The Oncologist 2016;21:28–32
对临床实践的提示: 乳腺神经内分泌癌 (NECB) 是一种独特的乳腺肿瘤。NECB 的临床特征和形态学均难以将其与其他乳腺癌亚型区分开来, 因此神经内分泌分化的免疫组化标记物 (主要是嗜铬粒蛋白和突触素) 应常规用于该病的确诊, 尤其是在怀疑可能与 NECB 相关的粘液性或实性乳头状癌中。辅助治疗应按照其他浸润性乳腺癌指南的建议实施。NECB 的准确诊断在转移性疾病中同样重要, 对于这类患者应考虑采用包括特异性治疗方案如多肽受体放射性核素治疗在内的多学科治疗方案。
This review discusses the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast. A multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination. A better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment.
To assess the outcomes of a cohort of bone oligometastatic prostate cancer patients treated with PSMA-PET guided stereotactic body radiotherapy (SBRT). From April 2017 to January 2021, 40 patients ...with oligorecurrent prostate cancer detected by PSMA-PET were treated with SBRT for bone oligometastases. Concurrent androgen deprivation therapy was an exclusion criterion. A total of 56 prostate cancer bone oligometastases were included in the present analysis. In 28 patients (70%), oligometastatic disease presented as a single lesion, two lesions in 22.5%, three lesions in 5%, four lesions in 2.5%. 30.3% were spine-metastases, while 69.7% were non-spine metastases. SBRT was delivered for a median dose of 30 Gy (24–40 Gy) in 3–5 fractions, with a median EQD
2
= 85 Gy
2
(64.3—138.9Gy
2
). With a median follow-up of 22 months (range 2–48 months), local control (LC) 1- and 2-years rates were 96.3% and 93.9%, while distant progression-free survival (DPFS) rates were 45.3% and 27%. At multivariate analysis, the lower PSA nadir value after SBRT remained significantly related to better DPFS rates (p = 0.03). In 7 patients, a second SBRT course was proposed with concurrent ADT, while 11 patients, due to polymetastatic spread, received ADT alone, resulting in 1- and 2-years ADT-free survival rates of 67.5% and 61.8%. At multivariate analysis, a lower number of treated oligometastases maintained a correlation with higher ADT-free survival rates (p = 0.04). In our experience, PSMA-PET guided SBRT resulted in excellent results in terms of clinical outcomes, representing a helpful tool with the aim to delay the start of ADT.
Purpose
The aim of this study is to analyze peptide receptors radionuclide therapy (PRRT) effectiveness in functioning malignant insulinomas poorly responsive to conventional therapies, by reviewing ...literature reports and combining them to our Center experience.
Method
Due to the rarity of this tumor, most literature is based on case reports. Overall, eight case reports and case series published between 2008 and 2019 were analyzed. A total of 34 patients affected by functioning metastatic insulinomas were evaluated. Among these, 33 patients were treated with 177Lu-DOTATATE and 1 patient received Indium-111 Octreotide.
Results
In terms of tumor growth control, 2 patient showed complete response to therapy (5.8%), 19 patients achieved partial response (55.9%), 8 patients presented stable disease (23.5%), and 5 patients progressed (14.7%). In terms of symptoms control, 24 out of 34 of patients (70.6%) reported a better glycemia level control, which is an important result that leads to a significant improvement of patients’ QoL. However, all these case reports profoundly differ between each other, in terms of treatment scheme, eligibility criteria and previous therapies. Therefore, it is extremely complex to statistically compare these studies and objectively evaluate the efficacy of this therapy in insulinomas, although, overall, it would seem to have a significant impact on the patient's QoL, PFS and tumor management.
Conclusions
In conclusion, PRRT resulted to be a very promising treatment for inoperable malignant insulinomas, in terms of patients’ quality of life improvement, clinical symptoms and tumor growth control. Further studies are needed, especially to evaluate its possible application as first-line therapy, in association with conventional therapies, which could lead to even better and longer-lasting results.
Around 30% Parkinson's disease (PD) patients develop impulse control disorders (ICDs) to D
dopamine agonists and, to a lesser extent, levodopa. We aim to investigate striatal dopaminergic function in ...PD patients with and without ICD.
PubMed, Science Direct, EBSCO, and ISI Web of Science databases were searched (from inception to March 7, 2018) to identify PET or SPECT studies reporting striatal dopaminergic function in PD patients with ICD (ICD+) compared to those without ICD (ICD-). Studies which included drug naïve patients, explored non-pharmacological procedures (e.g., deep brain stimulation), and those using brain blood perfusion or non-dopaminergic markers were excluded. Standardized mean difference (SDM) was used and random-effect models were applied. Separate meta-analyses were performed for dopamine transporter level, dopamine release, and dopamine receptors availability in the putamen, caudate, dorsal, and ventral striatum.
A total of 238 studies were title and abstract screened, of which 19 full-texts were assessed. Nine studies (ICD+:
= 117; ICD-:
= 175 patients) were included in the analysis. ICD+ showed a significant reduction of dopamine transporter binding in the putamen (SDM = -0.46; 95% CI: -0.80, -0.11;
= 2.61;
= 0.009), caudate (SDM = -0.38; 95% CI: -0.73, -0.04;
= 2.18;
= 0.03) and dorsal striatum (SDM = -0.45; 95% CI: -0.77, -0.13;
= 2.76;
= 0.006), and increased dopamine release to reward-related stimuli/gambling tasks in the ventral striatum (SDM = -1.04; 95% CI: -1.73, -0.35;
= 2.95;
= 0.003). Dopamine receptors availability did not differ between groups. Heterogeneity was low for dopamine transporter in the dorsal striatum (
= 0%), putamen (
= 0%) and caudate (
= 0%), and pre-synaptic dopamine release in the dorsal (
= 0%) and ventral striatum (
= 0%); heterogeneity was high for dopamine transporter levels in the ventral striatum (
= 80%), and for dopamine receptors availability in the ventral (
= 89%) and dorsal (
= 86%) striatum, putamen (
= 93%), and caudate (
= 71%).
ICD+ patients show lower dopaminergic transporter levels in the dorsal striatum and increased dopamine release in the ventral striatum when engaged in reward-related stimuli/gambling tasks. This dopaminergic imbalance might represent a biological substrate for ICD in PD. Adequately powered longitudinal studies with drug naïve patients are needed to understand whether these changes may represent biomarkers of premorbid vulnerability to ICD.
Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its ...role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa.
From 2016 to 2021, we treated a series of oligo-NSBM from PCa with
Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS).
a total of 150 NSBM in 95 patients were treated with 30-35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (
= 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (
= 0.001) and oligoprogressive patients (
= 0.007). No grade ≥ 3 toxicity occurred.
SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.
To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients.
A retrospective analysis was conducted on a cohort of patients ...with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months.
This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively.
Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.
Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene (MET) exon 14 skipping mutation has not been established yet. MET inhibitors were ...demonstrated to be effective and tolerated in patients with this condition, while evidence on safety and efficacy of immunotherapy and/or chemotherapy in this population is limited. Here we report the case of an 86-year-old male with metastatic NSCLC harboring MET exon 14 skipping mutation and with high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score ≥50%). The patient received the MET inhibitor tepotinib as first-line treatment, achieving a partial response, with G2 peripheral edema as adverse event that was successfully managed with temporary discontinuation, dose reduction, diuretics and physical therapy. After 31 months, the patient is still receiving tepotinib, with an ongoing response. Tepotinib is a valuable therapeutic option for first-line treatment of older patients with NSCLC harboring MET exon 14 skipping mutation, even in the presence of high PD-L1 expression.
The role of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in early breast cancer treated with preoperative systemic therapy (PST) is not yet established in ...clinical practice. PET parameters have aroused great interest in the recent years, as non-invasive dynamic biological markers for predicting response to PST.
In this retrospective study, we included 141 patients with stage II-III breast cancer who underwent surgery after PST. Using ROC analysis, we set optimal cutoff of FDG-PET/CT parameters predictive for pathological complete response (pCR). We investigated the correlation between FDG-PET/CT parameters and pCR, median disease-free survival (DFS), and median overall survival (mOS).
At multivariable analysis, baseline SUVmax (high vs low: OR 9.00, CI 1.85 - 61.9, p=0.012) and Delta SUVmax (high vs low: OR 9.64, CI 1.84, 69.2, p=0.012) were significantly associated with pCR rates. Interestingly, we found that a combined analysis of the metabolic parameter Delta SUVmax with the volume-based parameter Delta MTV, may help to identify patients with pCR, especially in the subgroup of hormone receptor positive breast cancer. Delta SUVmax was also an independent predictive marker for both mDFS (high vs low: HR 0.17, 95%CI 0.05-0.58, p=0.004) and mOS (high vs. low: HR 0.19, 95%CI 0.04-0.95, p=0.029).
Our results suggest that Delta SUVmax may predict survival of early BC patients treated with PST.
Objectives
Aim of the current study was to evaluate the relationships between the findings of 18F-fluoride PET/CT (F-PET/CT) reflecting osteo-proliferative processes and the clinical indexes related ...to the disease activity. The clinical indexes are Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS).
Methods
We studied 29 AS patients aged 26–69 years with a wide range of disease activity using F-PET/CT. The number of regions of high bone turnover or osteoarthritis features at the spine and at sacroiliac joints was counted.
Results
The number of F-PET/CT positive sites was significantly higher in patients with severe functional impairment and higher disease activity and it was positively related to both BASDAI (
r
= 0.336;
P
= 0.036) and ASDAS (
r
= 0.408;
P
= 0.014) while the number of degenerative features (osteoarthritis) was related neither with functional impact nor with disease activity.
Conclusions
With a single examination, F-PET/CT accurately identifies the functional impairment and the clinical involvement of AS. The good correlation we found between the number of F-PET/CT positive sites and disease activity candidates this technique also for follow-up of AS.
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