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Purpose: The objective of this study was to evaluate a set of radiomics-based advanced textural features extracted from 18F-FLT-PET/CT images to predict tumor response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (BC). Materials and Methods: Patients with operable (T2-T3, N0-N2, M0) or locally advanced (T4, N0-N2, M0) BC were enrolled. All patients underwent chemotherapy (six cycles every 3 weeks). Surgery was performed within 4 weeks of the end of NCT. The MD Anderson Residual Cancer Burden calculator was used to evaluate the pathological response. 18F-FLT-PET/CT was performed 2 weeks before the start of NCT and approximately 3 weeks after the first cycle. The evaluation of PET response was based on EORTC criteria. Standard uptake value (SUV) statistics (SUVmax, SUVpeak, SUVmean), together with 148 textural features, were extracted from each lesion. Indices that are robust against contour variability (ICC test) were used as independent variables to logistically model tumor response. LASSO analysis was used for variable selection. Results: Twenty patients were included in the study. Lesions from 15 patients were evaluable and analyzed: 9 with pathological complete response (pCR) and 6 with pathological partial response (pPR). Concordance between PET response and histological examination was found in 13/15 patients. LASSO logistic modelling identified a combination of SUVmax and the textural feature index IVH_VolumeIntFract_90 as the most useful to classify PET response, and a combination of PET response, ID range, and ID_Coefficient of Variation as the most useful to classify pathological response. Conclusions: Our study suggests the potential usefulness of FLT-PET for early monitoring of response to NCT. A model based on PET radiomic characteristics could have good discriminatory capacity of early response before the end of treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: We retrospectively investigated 18F-FDG uptake by the primary breast tumor as a predictor for relapse and survival. Patients and methods: We studied 203 patients with cT1-T3N0 breast cancer. Standardized uptake value (SUVmax), was measured on the primary tumor. After a median follow-up of 68 months (range 22–80), the relation between SUVmax and tumor factors, disease free-survival (DFS) and overall survival (OS) was investigated. Results: In the PET-positive patients, the median FDG uptake by the tumor was 4.7. FDG uptake was significantly related to tumor size, number of involved axillary nodes, grade, negative ER, high Ki-67 and HER2 overexpression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P = 0.096). At univariate analysis, DFS was significantly lower in patients with SUVmax >4.7 compared to the patients with negative PET (P = 0.042), but not to the patients with SUVmax ≤4.7 (P = 0.106). At multivariable analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS (HR>4.7 vs ≤4.7: 1.02 (95% CI 0.45–2.31)). Five-year OS was 100% and 93%, respectively, in the PET-negative and PET-positive groups (P = 0.126). Conclusion: FDG uptake by the primary lesion was significantly associated with several prognostic variables, but it was not an independent prognostic factor. [Copyright &y& Elsevier]

Purpose: The main objective of this study was to determine the role of [F]-2-fluoro-2-deoxy- D-glucose positron emission tomography (FDG PET) in the selection of patients with breast cancer as candidates for sentinel node biopsy (SNB) after neoadjuvant therapy. Methods: Forty-four patients with primary breast cancer clinically classified as cT2, cT3 or cT4 cN0-N2 or cN3 M0 and with a baseline FDG PET scan positive both in the site of primary tumour and axillary lymph nodes underwent neoadjuvant therapy and then a second FDG PET scan. In the case of axillary FDG PET uptake, patients underwent axillary lymph node dissection (ALND). If the second FDG PET scan was negative for axillary involvement, SNB was performed in order to evaluate axillary lymph node status. Only in the case of SN positivity did total ALND follow. Results: Specificity and positive predictive value of FDG PET for detection of axillary lymph node metastases after neoadjuvant therapy were as high as 83% (95% confidence interval: 51–97%) and 85% (95% confidence interval: 54–97%), respectively, whereas sensitivity, negative predictive value and diagnostic accuracy were inadequate for a correct staging (34, 32 and 48%, respectively). Conclusion: The poor sensitivity of FDG PET in detecting axillary lymph node metastases makes SNB mandatory in cases of a negative scan. The relatively high positive predictive value seems to suggest a role of FDG PET in selecting patients who, after neoadjuvant therapy, are candidates for ALND, avoiding SNB. However, this issue requires confirmation in a larger series of patients. [ABSTRACT FROM AUTHOR]

Vulvar melanoma is a rare malignant tumour. Its surgical excision is the mainstay of treatment whilst the surgical management of regional lymph nodes remains controversial; on the contrary elective inguinofemoral lymphadenectomy causes considerable morbidity. Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) are accurate staging procedures of lymph node status in breast cancer and cutaneous melanoma patients. In this retrospective paper we report our experience of LS and SLNB in vulvar melanoma patients. Twenty-two consecutive patients with a diagnosis of vulvar melanoma were treated at our institute: patients with clinically positive groin nodes or with previous surgery on the primary tumour were excluded. Twelve were selected for our analysis. All patients underwent sentinel lymph node localization with LS the day before surgery and the surgical procedure of SLNB associated with radical surgery. Six patients had metastatic SLNB and in five of six (83.3%) it was the only positive node. In the other six patients SLNB was negative for metastatic disease. No skip metastases were observed. In SLNB negative patients the mean Breslow thickness was 2.06 mm (range: 0.60–7.10) and only one patient showed a high Breslow thickness (patient 8). In SLNB positive patients the mean Breslow thickness was 4.33 mm (1.8–6.0). Our data indicate that, even in vulvar melanoma, the sentinel lymph node pathological status predicts the pathological status of the remaining groin nodes and suggests that elective groin dissection can be spared in cases of a negative SLNB. Breslow thickness (<1 mm) was not predictive of negative nodes. [ABSTRACT FROM AUTHOR]

External beam radiotherapy (EBRT) after conservative surgery for early breast cancer requires 5–7 weeks. For elderly patients and those distant from an RT center, attending for EBRT may be difficult or impossible. We investigated local toxicity, cosmetic outcomes, and quality of life in a new breast irradiation technique—intraoperative avidination for radionuclide therapy (IART)—in which avidin is administered to the tumor bed and 90Y-labelled biotin later administered intravenously to bind the avidin and provide irradiation. Reduced duration EBRT (40 Gy) is given subsequently. After surgery, 50 (ten patients), 100 (15 patients) or 150 mg (ten patients) of avidin was injected into the tumor bed. After 12-24 h, 3.7 GBq 90Y-biotin (beta source for therapeutic effect) plus 185 MBq 111In-biotin (gamma source for imaging and dosimetry) was infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to 30 h. Shortened EBRT started 4 weeks later. Local toxicity was assessed by RTOG scale; quality of life was assessed by EORTC QOL-30. Of 35 patients recruited (mean age 63 years; range 42–74) 32 received IART plus EBRT. 100 mg avidin provided 19.5 ± 4.0 Gy to the tumor bed and was considered the optimum dose. No side-effects of avidin or 90Y-biotin occurred, with no hematological or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART plus EBRT was well accepted, with good cosmetic outcomes and maintained quality of life. IART plus reduced EBRT can accelerate irradiation after conservative breast surgery. [ABSTRACT FROM AUTHOR]

The authors reflect on the usefulness and accuracy of sentinel lymph node biopsy (SLNB) in detecting the staging procedure in breast cancer patients. They explain that the said procedure is preferred and commonly practiced by most surgeons for breast cancer treatment. They also emphasize the importance of keeping medical records of the patients for further disease monitoring used. They believe that the SLN approach is an effective treatment procedure for breast cancer.

Summary: Sentinel lymph node biopsy (SLNB) is a staging technique with a significant impact on patients’ quality of life: the oncological effectiveness in a large number of patients affected by breast carcinoma has been already demonstrated, and the clinical research is now focusing on new indication for the biopsy and widespread adoption of the technique. At the European Institute of Oncology we are applying SLNB under local anesthesia: our aim is to improve the management of the disease with low costs for the structure and patients, and to improve patients’ acceptance of breast cancer treatments. We are now discussing the impact of the SLNB under local anesthesia on the activity of a breast surgery department. We also present an update of our experience. [Copyright &y& Elsevier]

Summary: Mammoscintigraphy (MMS) has been indicated as a useful tool in predicting response to therapy in cancer. However, contrasting results have been reported in the literature for breast cancer patients. The aim of this study was to explore the role of MMS in locally advanced breast cancer (LABC) patients. Fifty-one patients affected by LABC and scheduled for neoadjuvant therapy were enrolled. Breast tumor status was evaluated at baseline, during therapy and at the completion of therapy by radiological techniques and by MMS. Pre-therapy (MMS1) and post-therapy MIBI (2-methoxyisobutilysonitrile) images (MMS2–3) were analyzed. MMS1 was performed in all pts, 41 carried out MMS2 and 27 had MMS3. Tumor uptake and washout in MMS1 did not show any correlation with the therapy response. The absence of any association between tumor uptake and washout with respect to therapy response suggests that MMS is not a reliable technique to predict therapy response in LABC. [Copyright &y& Elsevier]

Summary: The profound revolution that surgical treatment of breast cancer has undergone during the past 30 years has led to the progressive reduction of the extent of surgery, with less mutilation. As a consequence, quality of life has improved and women are now more motivated to follow screening programs for early diagnosis of the disease. Since conservative surgery is as effective as radical surgery, research is now focused on reducing radiotherapy. Overall, survival after breast cancer is not affected by reducing the extent of surgery, which, together with less invasive diagnostic procedures, has a good effect on patients’ quality of life. For this reason in our Institute we are now evaluating the feasibility of a reduction of the radiation field and the sensibility and sensitivity of new diagnostic approaches for axillary staging. [Copyright &y& Elsevier]

Summary: A new procedure, known as Intraoperative Avidination for Radionuclide Therapy (IART®), is described in breast cancer patients. In this paper, we provide proof of the principle that intraoperative injection of avidin in the tumour bed after quadrantectomy allows homing in of intravenously (IV) administered radioactive biotin to the target site. This approach of targeted therapy consists of two steps: [(i)] “avidination” of the anatomical area of the tumour with avidin injected by the surgeon, into and around the tumour bed; [(ii)] targeting the anatomical area of the tumour by IV injection of radiolabelled biotin. The scintigraphic images demonstrated fast and stable uptake of labelled biotin at the site of operated breast. The radiation dose released to the index quadrant was more than 5Gy/GBq, consistent with a boost of 20Gy for an activity of 3.7GBq 90Y-biotin (100mCi). A further large clinical trial facing IART® in combination with reduced external-beam radiotherapy is, in our opinion, fully justified. [Copyright &y& Elsevier]

Summary: Background: In women with breast cancer, sentinel-lymph-node biopsy (SLNB) provides information that allows surgeons to avoid axillary-lymph-node dissection (ALND) if the SLN does not have metastasis, and has a favourable effect on quality of life. Results of our previous trial showed that SLNB accurately screens the ALN for metastasis in breast cancers of diameter 2 mm or less. We aimed to update this trial with results from longer follow-up. Methods: Women with breast tumours of diameter 2 cm or less were randomly assigned after breast-conserving surgery either to SLNB and total ALND (ALND group), or to SLNB followed by ALND only if the SLN was involved (SLN group). Analysis was restricted to patients whose tumour characteristics met eligibility criteria after treatment. The main endpoints were the number of axillary metastases in women in the SLN group with negative SLNs, staging power of SLNB, and disease-free and overall survival. Findings: Of the 257 patients in the ALND group, 83 (32%) had a positive SLN and 174 (68%) had a negative SLN; eight of those with negative SLNs were found to have false-negative SLNs. Of the 259 patients in the SLN group, 92 (36%) had a positive SLN, and 167 (65%) had a negative SLN. One case of overt clinical axillary metastasis was seen in the follow-up of the 167 women in the SLN group who did not receive ALND (ie, one false-negative). After a median follow-up of 79 months (range 15–97), 34 events associated with breast cancer occurred: 18 in the ALND group, and 16 in the SLN group (log-rank p=0·6). The overall 5-year survival of all patients was 96·4% (95% CI 94·1–98·7) in the ALND group and 98·4% (96·9–100) in the SLN group (log-rank p=0·1). Interpretation: SLNB can allow total ALND to be avoided in patients with negative SLNs, while reducing postoperative morbidity and the costs of hospital stay. The finding that only one overt axillary metastasis occurred during follow-up of patients who did not receive ALND (whereas eight cases were expected) could be explained by various hypotheses, including those from cancer-stem-cell research. [Copyright &y& Elsevier]

Internal mammary chain lymphnodes (IMNs) were studied by lymphoscintigraphy and biopsy in 100 breast cancer patients to assess:(i) if a deep injection can visualize the IMNs in a high percentage of cases(ii) to determine how often IMNs are metastatic.More than 60% of patients showed IMNs uptake. Surgical sampling proved simple and risks insignificant. Five positive IMN cases migrated from NO/N1 to N3, prompting treatment modification. It is unclear whether this additional information can lead to better survival. [Copyright &y& Elsevier]

An introduction is presented in which the editors discuss various reports within the issue on topics including the correlation between glycolytic characteristics of primary breast tumors and their subtypes, the assessment of hormone receptors in multicentre study, and the response of primary tumors to neoadjuvant chemotherapy.

Discusses the application of sentinel node biopsy on the diagnosis of breast cancer cells. Importance of the spread of tumor cells to axillary lymph nodes in the prognosis and therapy options in patients with breast cancer; Role of tumor size to the risk of metastases; Results of a study on the resection of sentinel nodes in breast cancer.

Background: Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. Methods: From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). Results: The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up. Conclusions: Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer. N Engl J Med 2003;349:546-53. [ABSTRACT FROM AUTHOR]

Abstract: Premises: Sentinel node biopsy (SNB) in patients with breast carcinoma accurately predicts the axillary node status. However, in some 4–7% of patients with negative sentinel nodes, the remaining axillary nodes harbour cancer cells. Objective: Our purpose was the long-term observation of a large number of patients who did not receive axillary dissection after a negative sentinel node biopsy, in order to evaluate the incidence of overt axillary metastases. Methods: Patients (3548) treated from 1996 to 2004, with negative sentinel nodes not submitted to axillary dissection, were followed up to 11 years with a median follow-up of 48 months. Results: Three hundred and sixteen unfavourable events occurred among the 3548 patients, 196 of which (5.5%) related to primary breast carcinoma. Thirty one cases of overt axillary metastases were found (0.9%): they received total axillary dissection and 27 of them are at present alive and well. The 5-year overall survival rate of the whole series was 98%. Conclusions: Patients with negative sentinel node biopsy not submitted to axillary dissection show, at follow-up, a rate of overt axillary metastases lower than expected. [Copyright &y& Elsevier]

Sentinel node biopsy in patients with breast carcinoma accurately predicts the axillary nodal status. However, in some 6% of patients with negative sentinel nodes the remaining axillary nodes harbour metastases. Our purpose was to observe a large number of patients who did not undergo an axillary dissection after a negative sentinel node biopsy for the appearance of overt axillary metastases. 953 patients treated from 1996 to 2000, with negative sentinel nodes not submitted to axillary dissection, were followed-up to 7 years, with a median follow-up of 38 months. Fifty-five unfavourable events occurred among the 953 patients, 37 (4%) related to the primary breast carcinoma. Three cases of overt axillary metastases were found: they received total axillary dissection and are presently alive and well. The 5 year overall survival rate of the whole series was 98%. Patients with negative sentinel node biopsies not submitted to axillary dissection show during follow-up a rate of overt axillary metastases that is lower than that expected. [Copyright &y& Elsevier]