Increasing opportunities for breast-conserving therapy in multiple ipsilateral breast cancer: Dutch nationwide study.

INTRODUCTION: An increasing number of breast cancer patients undergo breast-conserving surgery (BCS), but multiple ipsilateral breast cancer (MIBC) is still considered a relative contraindication for breast conservation. This study provides an update on trends in the surgical management for MIBC over a 10-year period. METHODS: Nationwide data from the Netherlands Cancer Registration of all patients diagnosed with breast cancer between 2011 and 2021 were analysed. The primary outcomes of this study were the incidence of MIBC and the trend in breast surgery type among patients between 2011 and 2021. Secondary outcomes were the positive resection margin rates in patients treated with BCS, the proportion of patients requiring re-excision and overall survival. RESULTS: In total, 114 433 patients (83%) with unifocal breast cancer and 23 932 patients (17%) with MIBC were identified. The incidence of MIBC was stable (17%) over the years. Overall BCS rates, both primary and after neoadjuvant chemotherapy, increased in MIBC from 29% in 2011 to 41% in 2021. Re-excision was performed in 1348 patients (n = 8455, 16%). The 5-year OS estimate for patients with MIBC treated with BCS was 93%. The pathological complete response (pCR) in MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy was 23%. CONCLUSION: The breast conservation rate in MIBC has increased over the last decade. In addition, 23% of MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy achieved a pCR. This suggests increasing opportunities for even more BCS in MIBC.

Moving beyond barriers: a mixed-method study to develop evidence-based strategies to improve implementation of PROMs in clinical oncology care.

PURPOSE: This study aimed to identify feasible, evidence-based strategies to improve the use of Patient-reported outcome measures (PROMs) implemented in clinical oncology practice. METHODS: A mixed-method study involving observations of consultations and semi-structured interviews with patients and healthcare professionals (HCPs) was conducted to identify facilitators and barriers for using PROMs; barriers and facilitators were structured following the Theoretical Domains Framework. For each barrier, evidence-based improvement strategies were selected using the Behaviour Change Techniques Taxonomy v1. Subsequently, improvement strategies were ranked on priority and feasibility by an expert panel of HCPs, information technology professionals, and PROMs implementation specialists, creating an implementation improvement strategy. RESULTS: Ten consultations were observed and 14 interviews conducted. Barriers for implementation included that the electronic health record and PROMs did not align to the individual needs of end users, the HCPs' hesitance to advice patients about health-related quality-of-life issues, and a lack of consensus on which HCPs were responsible for discussing PROMs with patients. Forty-one improvement strategies were identified, of which 25 remained after ranking. These included: redesigning the PROMs dashboard by including patient management advice, enhancing patient support to complete PROMs, and clarifying HCPs' responsibilities for discussing PROMs. Strategies currently considered less feasible were: improving user-friendliness of the patient portal due to technical constraints, aligning PROMs assessment frequency with clinical courses, and using baseline PROMs for early identification of vulnerabilities and supportive care needs. These will be studied in future research. CONCLUSION: Evidence-based improvement strategies to ensure lasting adoption of PROMs in clinical practice were identified.

Clinical implications of non-breast cancer related findings on FDG-PET/CT scan prior to neoadjuvant chemotherapy in patients with breast cancer.

PURPOSE: Breast cancer (BC) patients undergoing FDG-PET/CT scans for neoadjuvant chemotherapy (NAC) may have additional non-BC related findings. The aim of this study is to describe the clinical implications of these findings. METHODS: We included BC patients who underwent an FDG-PET/CT scan in our institute between 2011-2020 prior to NAC. We focused on patients with an additional non-BC related finding (i.e. BC metastases were excluded) for which diagnostic work-up was performed. Information about the diagnostic work-up and the clinical consequences was retrospectively gathered. A revision of all FDG-PET/CT scans was conducted by an independent physician to assess the suspicion level of the additional findings. RESULTS: Of the 1337 patients who underwent FDG-PET/CT, 202 patients (15%) had an non-BC related additional finding for which diagnostic work-up was conducted, resulting in 318 examinations during the first year. The non-BC related findings were mostly detected in the endocrine region (26%), gastro-intestinal region (16%), or the lungs (15%). Seventeen patients (17/202: 8%, 17/1337: 1.3%) had a second primary malignancy. Only 8 patients (8/202: 4%, 8/1337: 0.6%) had a finding that was considered more prognosis-determining than their BC disease. When revising all FDG-PET/CT scans, 57 (202/57: 28%) of the patients had an additional finding categorized as low suspicious, suggesting no indication for diagnostic work-up. CONCLUSION: FDG-PET/CT scans used for dissemination imaging in BC patients detect a high number of non-BC related additional findings, often clinically irrelevant and causing a large amount of unnecessary work-up. However, in 8% of the patients undergoing diagnostic work-up for an additional finding, a second primary malignancy was detected, warranting diagnostic attention in selected patients.

Intraoperative frozen section of subareolar tissue in nipple-sparing mastectomy: Towards a less is more approach.

BACKGROUND: Nipple preservation contributes to aesthetic outcome and quality of life in women undergoing Skin-Sparing Mastectomy (SSM) with immediate breast reconstruction for the treatment of breast cancer. Intraoperative Frozen Section (IFS) has been advocated to facilitate conversion from Nipple-Sparing Mastectomy (NSM) to SSM in cases with positive subareolar margins. This study investigated the application of IFS at our comprehensive cancer centre. METHODS: In this single-centre retrospective study, for all patients who underwent therapeutic NSM with IFS from 2000 to 2021 pathological reports, patient- and tumour characteristics were retrieved. RESULTS: In total 640 women were included in whom 662 intended NSMs with IFS had been performed. Sensitivity and specificity of frozen section compared with definitive histopathology were 75.2% and 98.5% respectively. In six women with a false positive result, the nipple had been removed. In 16 out of 32 women with a false negative result, the nipple was excised in a second procedure. In total 115 nipples were resected. In 40% of these nipples, no residual disease was detected. DISCUSSION: IFS is a moderately sensitive and highly specific diagnostic tool to detect positive subareolar margins. An alternative approach is to omit frozen section but take intraoperative biopsies of the sub areolar margin, which are postoperatively analysed with definitive formalin-fixed paraffin-embedded histopathology. This allows for shared decision making regarding nipple excision in cases where minimal disease is found in subareolar tissue or cases with an indication for post-mastectomy radiotherapy.

Breast surgery after neoadjuvant chemotherapy in patients with lobular carcinoma: surgical and oncologic outcome.

INTRODUCTION: Breast cancer patients with invasive lobular carcinoma (ILC) have an increased risk of positive margins after surgery and often show little response to neoadjuvant chemotherapy (NAC). We aimed to investigate surgical outcomes in patients with ILC treated with NAC. METHODS: In this retrospective cohort study, all breast cancer patients with ILC treated with NAC who underwent surgery at the Netherlands Cancer Institute from 2010 to 2019 were selected. Patients with mixed type ILC in pre-NAC biopsies were excluded if the lobular component was not confirmed in the surgical specimen. Main outcomes were tumor-positive margins and re-excision rate. Associations between baseline characteristics and tumor-positive margins were assessed, as were complications, locoregional recurrence rate (LRR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: We included 191 patients. After NAC, 107 (56%) patients had breast conserving surgery (BCS) and 84 (44%) patients underwent mastectomy. Tumor-positive margins were observed in 67 (35%) patients. Fifty five (51%) had BCS and 12 (14%) underwent mastectomy (p value < 0.001). Re-excision was performed in 35 (33%) patients with BCS and in 4 (5%) patients with mastectomy. Definitive surgery was mastectomy in 107 (56%) patients and BCS in 84 (44%) patients. Tumor-positive margins were associated with cT ≥ 3 status (OR 4.62, 95% CI 1.26-16.98, p value 0.021) in the BCS group. Five-year LRR (4.7%), RFS (81%), and OS (93%) were not affected by type of surgery after NAC. CONCLUSION: Although 33% of ILC breast cancer patients undergoing BCS after NAC required re-excision for positive resection margins, it is considered safe given that five-year RFS remained excellent and LRR and OS did not differ by extent of surgery.

The Safe Use of 125I-Seeds as a Localization Technique in Breast Cancer during Pregnancy.

INTRODUCTION: Some aspects of the treatment protocol for breast cancer during pregnancy (PrBC) have not been thoroughly studied. This study provides clarity regarding the safety of the use of 125I-seeds as a localization technique for breast-conserving surgery in patients with PrBC. METHODS: To calculate the exposure to the fetus of one 125I-seed implanted in a breast tumor, we developed a model accounting for the decaying 125I-source, time to surgery, and the declining distance between the 125I-seed and the fetus. The primary outcome was the maximum cumulative fetal dose of radiation at consecutive gestational ages (GA). RESULTS: The cumulative fetal dose remains below 1 mSv if a single 125I-seed is implanted at a GA of 26 weeks. After a GA of 26 weeks, the fetal dose can be at a maximum of 11.6 mSv. If surgery takes place within two weeks of implantation from a GA of 26 weeks, and one week above a GA of 32 weeks, the dose remains below 1 mSv. CONCLUSION: The use of 125I-seeds is safe in PrBC. The maximum fetal exposure remains well below the threshold of 100 mSv, and therefore, does not lead to an increased risk of fetal tissue damage. Still, we propose keeping the fetal dose as low as possible, preferably below 1 mSv.

Incidence of PSMA PET thyroid incidentaloma depends on analysis method and tracer.

OBJECTIVE: To investigate the incidences of prostate-specific membrane antigen (PSMA) thyroid incidentaloma (PTI) using different methods to define PTI, to compare the incidence of PTI among different PSMA PET tracers, and to evaluate the clinical consequences of PTI. METHODS: PSMA PET/CT scans in consecutive patients with primary prostate cancer were analyzed for the presence of PTI using a structured visual (SV) analysis reporting any elevated thyroidal uptake; a semi-quantitative (SQ) analysis using a SUVmax thyroid/bloodpool (t/b) ratio ≥ 2.0 as cutoff; and an analysis of PTI incidence in the clinical reports (RV analysis). RESULTS: A total of 502 patients were included. The incidence of PTIs was 22% in the SV analysis, 7% in the SQ analysis, and 2% in the RV analysis. PTI incidences differed significantly from 29 to 64% (SQ, resp. SV analysis) for [18F]PSMA-1007, 7 to 23% for [68Ga]PSMA-11, 2 to 8% for [18F]DCFPyL, and to 0% for [18F]PSMA-JK-7. The majority of PTI in the SV and SQ analyses consisted of diffuse (72-83%) and/or only slightly elevated thyroidal uptake (70%). Inter-observer agreement in the SV analysis was substantial (kappa = 0.76-0.78). During follow-up (median 16.8 months), there were no thyroid-related adverse events except in three patients. CONCLUSIONS: The incidence of PTI varies greatly among different PSMA PET tracers and is strongly dependent on the analysis method applied. PTI may safely be restricted to focal thyroidal uptake with a SUVmax t/b ratio ≥ 2.0. The clinical pursuit of a PTI must be weighed up to the expected outcome of the underlying disease. KEY POINTS: • Thyroid incidentalomas (PTIs) are recognized in PSMA PET/CT. • Incidence of PTI varies greatly among PET tracers and analysis methods. • Incidence of thyroid-related adverse events in PTI cases is low.

The co-occurrence of both breast- and differentiated thyroid cancer: incidence, association and clinical implications for daily practice.

BACKGROUND: Breast cancer (BC) and differentiated thyroid cancer (TC) are two common cancer types with the highest incidence in women. BC and TC can develop synchronous or metachronous and the occurrence of both is higher than expected by chance. This study aimed to examine the association between BC and TC in the Netherlands. METHODS: This is a retrospective cohort study during the period of 1989-2020 retrieved from the Netherlands Cancer Registry (NCR). Patients diagnosed with BC-TC and BC alone as control group and TC-BC and TC alone as control group were included. The primary outcome was the standardized incidence ratio (SIR) of BC-TC and TC-BC. Secondary outcomes included data on the demographics, type of malignancy, treatment and overall survival (OS). RESULTS: The incidence of TC among 318.002 women with BC (BC-TC) was 0.1% (423 patients) (SIR = 1.86 (95% CI: 1.40-2.32)) and the incidence of BC among 12,370 patients with TC (TC-BC) was 2.9% (355 patients) (SIR = 1.46 (95% CI: 1.09-1.83)). BC-TC patients were younger compared to the BC alone group at BC diagnosis (55 vs 60 years, p < 0.001). The age-adjusted odds ratio to develop TC was not significantly increased for patients who received chemotherapy and radiotherapy. Most TC cases were synchronous tumors after BC diagnosis (19%) with a TNM stage 1. Only 6% of the BC tumors after TC occurred synchronous with a TNM stage 1 in most cases. The OS of all groups was the most favorable in patients with both BC and TC compared to BC- and TC alone. CONCLUSION AND RELEVANCE: The SIR of TC after BC diagnosis and BC after TC diagnosis was higher than predicted based on the rates of the general population. TC and BC as second primary tumors were diagnosed in an early stage and did not affect overall survival. Therefore, Dutch women who have been treated for BC or TC require no special surveillance for their thyroid- and breast gland.

Retrospective analysis of PSMA PET/CT thyroid incidental uptake in adults: incidence, diagnosis, and treatment/outcome in a tertiary cancer referral center and University Medical Center.

PURPOSE: A prostate-specific membrane antigen (PSMA) thyroid incidentaloma (PTI) is an unexpected, PSMA-avid thyroid lesion, newly detected during the investigation of an unrelated condition using PSMA PET/CT. The aim of this study is to examine the incidence and clinical significance of PTI and the associated management strategies since the implementation of the PSMA PET/CT scan. METHODS: This study involves a retrospective cohort study of 61 PTI cases depicted on PSMA PET/CT scans performed between January 2016 and July 2021, almost exclusively for (re)staging prostate cancer. The medical records of the included cases were retrospectively reviewed and data of the PSMA PET/CT scans, primary malignancy, thyroid diagnostics, treatment, and follow-up were collected. RESULTS: PTI was reported in 1.1% of the patients who underwent oncologic PSMA PET/CT scans included in this study. Two PTI cases had a histologically proven thyroid cancer: one a benign thyroid lesion and one a metastasis of a renal cell carcinoma. In none of the cases in whom any form of further thyroid workup was withheld, the PTI became clinically relevant during follow-up (median 1.8 years (1.1-3.3)). Six patients (10%) died due to their primary cancer. CONCLUSION: The incidence of thyroid incidentalomas on PSMA PET/CT was low (1.1%) in this large, two-center experience. Less than half of the PTI cases were analyzed and the risk of malignancy, despite being low, was not negligible. The clinical outcome was good using a standard diagnostic workup for PTI, while the prognosis of the patient was determined by the primary malignancy. The consideration to analyze and treat PTI cases should be part of the shared decision-making in cancer patients.

Retrospective Analyses of 18FDG-PET/CT Thyroid Incidentaloma in Adults: Incidence, Treatment, and Outcome in a Tertiary Cancer Referral Center.

Background: A thyroid incidentaloma (TI) is an unexpected, asymptomatic thyroid lesion discovered during the investigation of an unrelated condition. The aim of the present study is to examine the incidence of 18Fluorodeoxyglucose (FDG)-positron emission tomography (PET) TI, the associated management strategies and the outcomes in a tertiary cancer referral center. Methods: This study involves a retrospective cohort study of 1003 patients with TI found on 18FDG-PET/CT scans performed between January 2010 and January 2020 for a nonthyroidal malignancy. The Kaplan-Meier method was used for survival analyses in patients concerning an underlying malignancy, with a prevalence of 5% or higher in this cohort. Logistic- and cox regression analyses were performed to analyze predictors of thyroid malignancy and mortality. A propensity score weighted method was used to control for baseline differences between the intervention (additional TI diagnostics) and control (no TI diagnostics) group. Results: FDG-positive TI occurred in 1.9% (1003/52,693) of the oncologic 18FDG-PET/CT scans performed in our center. Thyroid surgery was performed in 47 patients (6%) and a thyroid malignancy was detected in 31 of them, which is 66% of those who had an operation and 4% of all patients. During the follow-up (median 6 years), 334 deaths (42%) related to different types of cancer (38%) or other causes (4%) were observed. One patient died from medullary thyroid cancer. In multivariate analysis adjusted for age, gender and the type- and stage of nonthyroidal malignancy, were independent predictors of survival (P < .05). Conclusions: The incidence of TI in this tertiary cancer referral center was comparable to current literature. Further thyroid workup was performed in less than half of the patients, and only a minority of patients underwent thyroid surgery. Since only one patient died from thyroid cancer, the strategy to withhold from thyroid diagnostics and treatment seems valid for most TI. Active thyroid treatment might benefit a subgroup of patients in whom the primary nonthyroidal malignancy is successfully treated or presumably stable. A wait-and-see policy with ultrasound follow-up could be an alternative strategy. These considerations should be part of the shared decision making in cancer patients with a TI.