Role of Qualitative and Quantitative Indocyanine Green Angiography to Assess Mastectomy Skin Flaps Perfusion: A Prospective Monocentric Experience.

INTRODUCTION: Mastectomy skin flap (MSF) necrosis remains a significant complication in breast reconstruction. This study aims to identify a correlation between the qualitative and quantitative analysis of the MSF perfusion grade and the skin necrosis rate 1 month after surgery using indocyanine green angiography (ICGA), focusing on lag time and perfusion metrics. METHODS: Consecutive women scheduled for nipple/skin-sparing/skin-reducing mastectomy between May 2020 and October 2022 were prospectively enrolled. Patients were divided into Group 1 in the absence of superficial and full-thickness necrosis (SN; FTN) and Group 2 in the presence of both. Demographic data, lag time T1 (time between ICG injection and the initial perfusion of the least perfused MSF area), ICG-Q1, and ICG-Q% (absolute and relative perfusion values of the least vascularized area) were collected. RESULTS: 76 breasts were considered. FTN was reported in 8 breasts (10.5%) and SN in 4 (5.2%). The 2 groups statistically differ in T1 (Group2 > Group1), ICG-Q1, and ICG-Q% (Group1 > Group2) (P < 0.05). T1 longer than 170 seconds, body mass index, previous chemo/radiotherapy, arterial hypertension, breast weight, type of surgery, and ICG quantitative values can help in predicting MSF necrosis. CONCLUSIONS: MSF qualitative and quantitative perfusion evaluation can be helpful to prevent MSF necrosis. However, it should be considered together with the patient's characteristics, the type of surgery, and T1. In this way, it is possible to predict the risk of MSF necrosis and plan the best reconstructive strategy.

Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

Near-infrared indocyanine green fluorescent cholangiography in urgent and emergency laparoscopic cholecystectomy: a preliminary study after propensity score-matched study.

INTRODUCTION: Bile duct injury is a major complication of laparoscopic cholecystectomy (LC). Indocyanine green near-infrared fluorescence cholangiography (ICG-NIFC) is a well-recognized technique who provides an intraoperative mapping of the biliary system. METHODS: All patients underwent urgent LC and randomly divided into two groups: in one group, only white light imaging was used and, in the ICG group, ICG was used. Due to the heterogeneity of our groups, a PSM was performed with a 1:1 PSM cohort. RESULTS: The use of ICG clearly decreases the operation time (p value 0.002). The overall rate of intra- and post- operative complications was 4.17% and 15.8% respectively. Post-operative biliary duct injury trend decreases in ICG group and after the homogenization of the 2 cohorts, the intra- and post- operative complications (including vascular and biliary duct injury) results changed with a highest rate of complication in the cohort with no-ICG administration. The use of NIFC demonstrated a protective effect against intra- and post- operative complications and biliary duct injury (HR 0.037, p value 0.337 and HR 0.039, p value 0.647; HR 0.288; p value 0.05 and HR 0.635; p value 0.687, respectively). CONCLUSIONS: The intra-operative use of NIFC showed a trend in the reduction of the rate of intra- and post-operative complications, the duration of surgery, and the length of hospital stay. ICG is a highly safe approach to urgent and emergency LC, as for elective LC, and could lead the surgeon to conduct the procedure more efficiently.

Presence and Role of Associations of Cancer Patients and Volunteers in Specialist Breast Centres: An Italian National Survey of Breast Centres Associated with Senonetwork.

This article aims to present the results of a national, cross-sectional, voluntary, online survey on the presence and roles of associations of breast cancer patients and volunteers in Italian specialist breast centres. The survey was developed according to standard methods. The questionnaire was pre-tested by a random sample of three breast centres, loaded onto the SurveyMonkey platform, and piloted by one volunteer breast centre. The breast centre clinical leads were invited to participate via email. A link to the online instrument was provided. No financial incentives were offered. The results were reported using standard descriptive statistics. The response rate was 82/128 (65%). Members of associations were routinely present in 70% Italian breast centres. Breast centres most often reporting their presence were those certified by the European Society of Breast Cancer Specialists. Patient support (reception and information, listening, identification of needs, and psychological support) was the primary area where associations were reported to offer services. The magnitude of this phenomenon warrants a study to investigate the impact of the activities of associations on the quality of life of patients and on the cost-benefit ratio of the service, and the modes of their interactions with the nursing staff and the medical staff.

Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications.

The poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate its potential progression and discover biomarkers related to patient survival. In this review, the NGS applications in TNBC research are described. Many NGS studies point to TP53 mutations, immunocheckpoint response genes, and aberrations in the PIK3CA and DNA repair pathways as recurrent pathogenic alterations in TNBC. Beyond their diagnostic and predictive/prognostic value, these findings suggest potential personalized treatments in PD -L1-positive TNBC or in TNBC with a homologous recombination deficit. Moreover, the comprehensive sequencing of large genomes with NGS has enabled the identification of novel markers with clinical value in TNBC, such as AURKA, MYC, and JARID2 mutations. In addition, NGS investigations to explore ethnicity-specific alterations have pointed to EZH2 overexpression, BRCA1 alterations, and a BRCA2-delaAAGA mutation as possible molecular signatures of African and African American TNBC. Finally, the development of long-read sequencing methods and their combination with optimized short-read techniques promise to improve the efficiency of NGS approaches for future massive clinical use.

Neoadjuvant systemic treatment in breast cancer surgery: is it always worth it?

BACKGROUND: Surgeons perspective of breast cancer (BC) treatment has deeply changed in recent time. We investigated survival outcomes of BC patients who underwent Neoadjuvant systemic treatment (NAT) before surgery and to assess the role of NAT in determining possible prognosis. METHODS: We retrospectively analyzed a total of 2372 BC patients consecutively enrolled in our prospective institutional database. Seventy-eight patients over 2372 reached the inclusion criteria and underwent surgery after NAT. RESULTS: After NAT, the 50% of luminal-B-HER2+ and the 53% of HER2+ had a pathological complete response (pCR) and only 18.5% of the TNs had a pCR. NAT significantly changed lymph node status (P=0.05). All women with pCR are still alive (No-pCR 0.732 CI: 0.589-0.832; yes-pCR 1.000 CI: 1.00-1.00; P=0.02). The molecular biology of the tumor, after NAT, is strictly related to survival both for 3- and 5-years OS. A triple negative BC have the worst prognosis (HER2+ 0.796 CI: 0.614-1; Luminal-A: 1 CI:1-1; LuminalB-HER2 -: 0.801 CI: 0.659-0975; LuminalB-HER2+: 1 CI:1-1; TN 0.542 CI: 0.372-0789, P=0.002). CONCLUSIONS: We can state that, based on our experience, we can consider safe and effective conservative interventions following neoadjuvant therapy. An adequate selection of patients is crucial. It is also clear how the planning of the therapeutic path plays a key role in an interdisciplinary context. NAT is a source of hope for the future both for the identification of new predictors of prognosis and in the field of research, for the development of new drugs.

A Case-Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection.

BACKGROUND: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI). METHODS: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder. RESULTS: Cases had significantly lower ALU 260/111 or LINE-1 266/97 copy number ratios (median; ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median; ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62-0.76 for ALU and 0.80, 95% CI: 0.73-0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with ALU. CONCLUSIONS: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker.

An Overview of Circulating Cell-Free Nucleic Acids in Diagnosis and Prognosis of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer due to its molecular heterogeneity and poor clinical outcomes. Analysis of circulating cell-free tumor nucleic acids (ctNAs) can improve our understanding of TNBC and provide efficient and non-invasive clinical biomarkers that may be representative of tumor heterogeneity. In this review, we summarize the potential of ctNAs to aid TNBC diagnosis and prognosis. For example, tumor fraction of circulating cell-free DNA (TFx) may be useful for molecular prognosis of TNBC: high TFx levels after neoadjuvant chemotherapy have been associated with shorter progression-free survival and relapse-free survival. Mutations and copy number variations of TP53 and PIK3CA/AKT genes in plasma may be important markers of TNBC onset, progression, metastasis, and for clinical follow-up. In contrast, the expression profile of circulating cell-free tumor non-coding RNAs (ctncRNAs) can be predictive of molecular subtypes of breast cancer and thus aid in the identification of TBNC. Finally, dysregulation of some circulating cell-free tumor miRNAs (miR17, miR19a, miR19b, miR25, miR93, miR105, miR199a) may have a predictive value for chemotherapy resistance. In conclusion, a growing number of efforts are highlighting the potential of ctNAs for future clinical applications in the diagnosis, prognosis, and follow-up of TNBC.

Central Mound Technique in Oncoplastic Surgery: A Valuable Technique to Save Your Bacon.

INTRODUCTION: Breast-conserving surgery (BCS) is a valid method for the reconstruction of partial breast defects, however, there is a great variety of final aesthetic outcomes depending on the location of the tumor in the breast and also on the initial breast volume and the degree of ptosis. Specifically, defects affecting the upper inner/central quadrant represent a reconstructive challenge with not always satisfactory final results. For this purpose, the authors investigated the use of the central mound technique in breast-conserving surgery. The aim of the study was to apply the central mound as an oncoplastic technique and assess the satisfaction rate of the patients. MATERIALS AND METHODS: This was a retrospective study that involved 40 patients (80 breast) underwent breast conserving surgery and contextual bilateral breast remodeling with central mound technique. A pre- and postoperative Breast-Q questionnaire (breast conserving therapy module) was given to all the patients before the surgery, 3 months and 9 months after. The statistical analysis with chi-square test was performed. RESULTS: After 9 months the author found a major increase of all BREAST-Q parameters; the most valuable increments concerned the "Satisfaction with breast" and "Psychosocial well-being." None of the patients experienced a decreased in the quality of life related to the surgical procedure. CONCLUSION: The authors believe that this technique has useful functional and aesthetic results particularly appreciated by patients with upper pole lesion who have a slightly or moderately breast ptosis and a small cup size.

Survival and long-term surgical outcomes after colorectal surgery: are there any gender-related differences?

Colorectal cancer (CRC) incidence and mortality seems to be lower in women than in men. The present study aims to evaluate the impact of gender on CRC diagnosis, treatment, and survival. This is a retrospective cohort study based on a single-center dataset of CRC patients from the University Hospital of Trieste (Italy). Data of 1796 consecutive CRC patients referred to our center from November 11th, 2004, to December 31st, 2017, were analyzed. Right-sided carcinomas are more frequent in women than in men; furthermore, women had a lower surgical complication rate. Men showed a higher 5- and 10-year mortality. This survival benefit for women was observed independently of the tumor localization. The 5-year hazard ratio (HR) for women vs men was 0.776 (p 0.003), and after 10-year 0.816 (p 0.017). Regarding the disease-free survival (DFS), 5 and 10-year HR was 0.759 (p 0.034) and 0.788 (p 0.07), respectively. On multivariable analysis, respecting tumor localization, the odds of female gender were higher than man with right colon disease. Male gender was more independently associated with age at the surgery time. Women survival advantage was higher than men, except for patients older than 80. Surgical outcome and survival after CRC surgical treatment seem to be gender related. For this reason, gender could play an important role in CRC diagnosis and therapy, allowing an earlier diagnosis in women.

Role of Qualitative and Quantitative Indocyanine Green Angiography to Assess Mastectomy Skin Flaps Perfusion in Nipple/Skin-Sparing and Skin-Reducing Mastectomies with Implant-Based Breast Reconstruction.

Methods: Consecutive women scheduled for nipple/skin-sparing/skin-reducing mastectomy between May 2020 and April 2021 were prospectively enrolled. Patients were divided into Group 1 in the absence of superficial and full-thickness necrosis (SN; FTN) and Group 2 in the presence of both. T1 (time between ICG injection and the initial perfusion of the least perfused MSF area), ICG-Q1, and ICG-Q% (absolute and relative perfusion values of the least vascularized area) were collected. Results: 38 breasts were considered. FTN was reported in 4 breasts (10.5%) and SN in 3 (7.9%). The two groups statistically differ in T1 (Group2 > Group1) and ICG-Q% (Group1 > Group2) (p < 0.05). T1 could statistically predict ICG-Q1 and ICG-Q%. Both quantitative values have a sensitivity of 57% and a NPV of 89%; ICG-Q% shows higher specificity (81% vs 77%) and PPV (40% vs 36%). Conclusions: Quantitative ICG angiography may additionally reduce MSF necrosis. Moreover, longer T1 may indicate possible postoperative necrosis. Considering these factors, intraoperative changes of reconstructive strategy could be adopted to reduce reconstructive failure.

Integrating mammography screening programmes into specialist breast centres in Italy: insights from a national survey of Senonetwork breast centres.

BACKGROUND: Despite recommendations, mammography screening is often insufficiently integrated into specialist breast centres. A national, cross-sectional, voluntary, online survey on this issue was carried out among the Italian breast centres associated with Senonetwork, the Italian network of breast cancer services. METHODS: A 73-item questionnaire was created, pre-tested and piloted. Centres integrating and not integrating a screening programme were compared using the unified theory of acceptance and use of technology (UTAUT) model. Centres' clustering was performed using the Gower's distance metric. Groups and clusters were compared with the equality-of-means test. RESULTS: The response rate was 82/128 (65%). Overall, 84% (69/82) breast centres reported a collaboration with a screening programme in performing and/or reading mammograms and in the diagnostic work-up of women with abnormal screening results. The same proportion was observed among those centres responding to all questions (62/74). Performance expectancies (or the perceived usefulness of integration in terms of clinical quality, patient convenience, ease of job, and professional growth), satisfaction and motivation were higher in those centres collaborating with the screening programme. Effort expectancy indicators (or the degree to which the respondents believe that the integration is easy to implement) and those concerning the existence of facilitating conditions were lower both in centres collaborating and not collaborating with the screening programme. Among the former, six clusters of centres, distributed from 'no integration' to 'high', were identified. In cluster analysis, the highest level of integration was associated with higher agreement that integration eases the job, offers better opportunities for professional growth, and makes the working environment more satisfactory. The least integrated cluster assigned the lowest score to the statement that local health authority made available the resources needed. CONCLUSIONS: While confirming the positive effects of integrating screening programmes into breast centres, this survey has brought to light specific difficulties that must be faced. The results provide insights into the importance of integration focusing on the perspectives of professional career and motivation. The deficiency of facilitating conditions to integration is modifiable. Screening professionals' societies may have a role as initiators of the integration. Other supporting actions may be included in health laws at the national and regional level.

The real-word impact of breast and colorectal cancer surgery during the SARS-CoV-2 pandemic.

The postponing of screening and the health care system reorganization, due to the Covid-19 pandemic and lockdown, could led to a concerning decline in breast and colorectal cancer diagnoses. This monocentric retrospective analysis has compared the pre-Covid period (March 2019 to March 2020) to the Covid period (April 2020 to April 2021) in terms of screening programs, clinical, surgical and pathological. A total of 799 patients diagnosed with Breast Cancer (BC) and Colorectal Cancer (CRC) underwent surgery during the two periods. In FVG in 2020 a decrease in mammography screening of 17.1% has been registered compared to 2019; this reduction has been higher for CRC screening, which summed up to 24.5%. As far as BC is concerned, screening-detected tumours rose significantly from 18 to 28%, mastectomies decreased from 40 to 31% and advanced tumours treated surgically decreased from 12 to 6%. Concerning CRC, a significant increase in admissions through the Emergency Department has been registered in spite of a stable percentage of urgent surgery performed, proving that severely symptomatic patients have been treated adequately. Open surgery has significantly decreased, whereas the tumoral stage and complications have remained constant in the two periods. This study has proved that maintaining standards of care and validated protocols during emergency is the most adequate and winning strategy: impact on BC and CRC has been less important than expected. These results support the recommendations for immediate and rapid screening program resumption at operating speed, using prioritization strategies to make up for the diagnostic delays.

The Added Value of Intraoperative Near-Infrared Fluorescence Imaging in Elective Laparoscopic Cholecystectomy.

Bile duct injury is a major complication of laparoscopic cholecystectomy (LC). Intraoperative cholangiogram is useful, but faster techniques are available to assist the surgeon, like near-infrared fluorescent cholangiography (NIFC) with indocyanine green (ICG). The aim of our study is to evaluate the usefulness of NIFC during LC. This is a retrospective study conducted on prospectively recorded data of the General Surgery department of Trieste Academic Hospital, Italy. All patients underwent elective LC from January 2016 to January 2020. Patients were randomly divided in 2 groups: in one group, only white light imaging was used (n = 98 patients), in the NIFC group (n = 63) ICG was used. NIFC has been chosen more frequently by residents than consultants (P = .002). Operative time and length of stay resulted shorter in ICG group (P = .002 and .006), and this group showed also fewer intraoperative complications (P = .007). NIFC does not require any learning curve and makes surgery faster and safer.

Anastomosis Leak: Is There Still a Place for Indocyanine Green Fluorescence Imaging in Colon-Rectal Surgery? A Retrospective, Propensity Score-Matched Cohort Study.

Anastomotic leakage (AL) represents one of the most relevant complications of colorectal cancer surgery. The aim of this study was to evaluate the utility of intraoperative indocyanine green (ICG) fluorescence imaging in the prevention of AL during laparoscopic colorectal surgery. Methods. We retrospectively analyzed 272 patients who underwent rectal and left colon surgery, consecutively enrolled between 2015 and 2019. Due to the heterogeneity of our groups, a propensity score matching (PSM) was performed with a 1:1 PSM cohort. Results. AL occurred in 36 (13.2%) patients. One hundred seventy-seven (65%) of them underwent an intraoperatory ICG test (ICG-group), whereas 95 patients (35%) did not receive the intraoperatory ICG test (no-ICG group). AL occurred in 10.8% of ICG group patients and in 17.8% of no-ICG group patients (P = 0.07). The ICG group registered significantly less type B and type C fistulas than the no-ICG group (57.9 vs 88.2%; P = .043). After PSM, the overall AL rate was less in the ICG group than the no-ICG group (9.3% vs 16%; P = 0.058), while type B and type C fistulas occurred in 5.48% in the ICG group vs 13.70% in the no-ICG group (P = 0.09). Univariate analysis demonstrated a protective effect of intraoperative ICG imaging against AL occurrence (odds ratio (OR: 0.66)). Conclusions. Hypoperfusion is a well-recognized cause of AL. The ICG assessment of colic vascularization is a simple, inexpensive, and side effects free method, which can sensibly reduce both overall AL and type B and type C fistulas when routinely used.

Comparison between male and female breast cancer survival using propensity score matching analysis.

Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management.

State of the art in breast intraoperative electron radiation therapy after intraoperative ultrasound introduction.

BACKGROUND: Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation - APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. PATIENTS AND METHODS: B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. RESULTS: From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). CONCLUSIONS: IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

Serum carcinoembryonic antigen pre-operative level in colorectal cancer: revisiting risk stratification.

BACKGROUND: Biomarkers may play a role as predictive and prognostic factors in colorectal cancer patients. The aims of the study were to verify the prognostic role of pre-operative serum carcinoembryonic antigen (CEA) level in predicting overall survival and risk of recurrence in a cohort of colorectal cancer patients and to evaluate optimal cut-off values. METHODS: A retrospective cohort analysis was performed on colorectal cancer patients undergoing elective curative surgery between 2004 and 2019 at an Italian Academic Hospital. Main outcomes were overall survival, disease-free survival at 3-years and risk of local, loco-regional and distant recurrence during follow-up. A receiver operating characteristic (ROC) curve analysis was plotted using CEA pre-operative values and follow-up data in order to estimate the optimal cut-off values. RESULTS: A total of 559 patients were considered. The mean CEA value was 12.1 ± 54.1 ng/mL, and the median 29.3 (0-4995) ng/mL. The ROC curve analysis identified 12.5 ng/mL as the best CEA cut-off value to predict the risk of metastatic development after surgery in stage I-III colorectal cancer patients, and 10 ng/mL as the best CEA cut-off value to predict overall survival and disease-free survival in stage III-IV patients. These data suggest a stratification of colorectal cancer patients in three classes of risk: a low risk class (CEA <10 ng/mL), a moderate risk class (CEA 10-12.5 ng/mL) and a high risk class (CEA >12.5 ng/mL). CONCLUSION: In conclusion, pre-operative serum CEA measurements could integrate information to enhance patient risk stratification and tailored therapy.

Direct comparison of three different mathematical models in two independent datasets of EUSOMA certified centers to predict recurrence and survival in estrogen receptor-positive breast cancer: impact on clinical practice.

PURPOSE: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI). METHODS: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent. RESULTS: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power. CONCLUSION: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS.

Pre-analytics, a national survey of Senonetwork Italia breast centers: Much still to do ahead.

INTRODUCTION: Pre-analytics involves handling and processing of microbiopsy and surgical specimen. It is critical for the preservation of morphology and the integrity of molecular markers, which are paramount as prognostic and predictive factors in breast cancer. Although pre-analytical variables in breast cancer are codified by national and international guidelines, there is currently no data on their actual endorsement in clinical practice among Breast Units (BU). MATERIALS AND METHODS: An anonymous questionnaire was sent by e-mail by Senonetwork Italia, a no-profit organization representing the multidisciplinary network of BU in Italy. The questionnaire involved twenty-four questions concerning critical issues related to the average time and transport temperature of the samples, monitoring of warm and cold ischemia, average fixation time for biopsies and surgical specimens, inking of the margins, and radiography of the operating sample. RESULTS: Forty-nine of 113 affiliated BU (43%), involved in the management of 44% of all breast cancer treated every year in Italy, answered the questionnaire. More than 90% of the BU reported a biopsy/VABB fixation time between 6 and 24 h. Only 41% of the Centers received the fresh operative sample to be sectioned immediately, 20% used the vacuum method and the sample arrived in the laboratory within 24-72 h. Delay in sectioning the sample was reported in as many as 40% of BU, while hot and cold ischemia time was monitored in only 4.2% and 6.2% of BU, respectively. CONCLUSION: Critical issues on pre-analytics are reported by the majority of dedicated BU in Italy. This represents a major challenge regarding quality of care, and improvements are needed in order to obtain valid and reproducible results of prognostic and predictive factors.