ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer.

Importance: There are insufficient data comparing 16α-18F-fluoro-17ß-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. Objective: To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. Design, Setting, and Participants: This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Exposure: Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. Main Outcomes and Measures: The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. Results: A total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13). Conclusions and Relevance: In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT).

INTRODUCTION: Intraoperative radiotherapy (IORT) permits accurate delivery of radiation therapy directly to the tumor bed. We report local, regional, and distant recurrence data along with overall and breast cancer-specific survival for 1400 tumors treated with x-ray IORT. METHODS: A total of 1367 patients with 1400 distinct tumors were enrolled in a registry trial. All received breast conservation surgery and low-energy 50 kV x-ray IORT. To be eligible for excision plus IORT as the only local treatment, histopathology had to confirm tumor size ≤30 mm, margins ≥2 mm, negative lymph nodes, and no extensive lymphovascular invasion. Patients who failed any parameters were referred for additional surgery and/or whole breast radiation therapy (WBRT). RESULTS: There were 64 ipsilateral local recurrences, 60 were in the IORT only group, 7 axillary recurrences, and 7 distant recurrences. Forty-one local recurrences were within the same quadrant as the index cancer. Twenty-three were in different quadrants. With 62 months of median follow-up, the 5-year Kaplan-Meier probability of any event for all 1400 tumors was 5.27%. For 1175 patients who received IORT only, it was 5.98%. For favorable subtypes, it ranged from 2.41 to 4.31%. Multivariate analysis revealed that biologic subtype luminal A and the addition of WBRT significantly reduced the risk of local recurrence. CONCLUSIONS: The local, regional, and distant recurrence rates observed were comparable to those reported in the literature for IORT but higher than those reported for standard forms of WBRT, hypofractionated treatment, or APBI. IORT benefits include convenience, decreased exposure to medical environments, and low complication rates.

Autologous mastectomy reconstruction: Communication among the breast surgery team to maximize aesthetic and oncologic outcome.

Mastectomy breast reconstruction with autologous tissue is challenging. Oncologic and aesthetic goals face previous surgical scars, radiation, chemotherapy, or other comorbidities. We describe a simple approach for autologous mastectomy reconstruction so that breast and plastic and reconstructive surgeons can maximize aesthetic outcomes and minimize wound complications. A retrospective chart review was done on patients who underwent mastectomy and autologous reconstruction. The surgical flight plans were reviewed to delineate an approach, and pre- and postoperative photographs were examined to create a step-by-step process. The most encountered mastectomy and autologous flap reconstruction scenarios were categorized to create a step-by-step process. Successful autologous mastectomy reconstruction to optimize aesthetic outcome and minimize complications requires team communication. Creation of a surgical flight plan using information from the physical examination, MRI and adjunctive imaging, and preoperative photographs is imperative. Thoughtful incision choice and exposure approach are paramount.

Intraoperative Radiation Therapy (IORT): A Series of 1000 Tumors.

BACKGROUND: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy to be a safe alternative, with a low-risk of local recurrence, compared with whole breast radiation therapy, following breast-conserving surgery, for selected low-risk patients. We report the first 1000 tumors treated with this modality at our facility. METHODS: A total of 1000 distinct breast cancers in 984 patients (16 bilateral) were treated with breast conserving surgery and X-ray IORT from June 2010 to August 2017. Patients were enrolled in an IORT registry trial. Local recurrence was the primary endpoint. RESULTS: There have been 28 ipsilateral local recurrences, ten DCIS and 18 invasive. Four local recurrences were within the IORT field, 13 outside of the IORT field but within the same quadrant as the index cancer, and 11 were new cancers in different quadrants. There have been four regional nodal recurrences and one distant recurrence. There have been no breast cancer related deaths and 14 non-breast cancer deaths. With a median follow-up of 36 months, Kaplan-Meier analysis projects 3.9% of patients will recur locally at 4 years. This includes all ipsilateral events in all quadrants. CONCLUSIONS: The local, regional, and distant recurrence rates observed in this trial were comparable to those of the prospective randomized TARGIT-A and ELIOT trials. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of X-ray IORT in women with low-risk breast cancer.

Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A Single Site Trial.

INTRODUCTION: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative to whole breast radiation therapy following breast-conserving surgery for selected low-risk patients. However, minimal data are available about the clinical effectiveness of this modality of treatment using the Xoft® Axxent® Electronic Brachytherapy (eBx®) System®. METHODS: A total of 201 patients with 204 early-stage breast cancers were enrolled in a prospective X-ray IORT trial from June 2010 to September 2013. All tumors were treated with breast-conserving surgery and IORT. Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. RESULTS: With a median follow-up of 50 months, there have been seven ipsilateral breast tumor events (IBTE), no regional or distant recurrences, and no breast cancer-related deaths. One IBTE was within the IORT field, four outside of the IORT field but within the same quadrant as the index cancer, and two were new biologically different cancers in different quadrants. Three events were in patients who deviated from the protocol criteria. Kaplan-Meier analysis projects that 2.9% of patients will recur locally at 4 years. CONCLUSIONS: Recurrence rates observed in this trial were comparable to those of the TARGIT-A and ELIOT trials as well as the retrospective TARGIT-R trial. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of IORT in selected women with low-risk breast cancer.

Acute and Chronic Complications in Patients with Ductal Carcinoma in Situ Treated with Intraoperative Radiation Therapy.

Intraoperative radiation therapy (IORT) delivers radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available regarding IORT complications in patients diagnosed with ductal carcinoma in situ (DCIS) using the Xoft® Axxent eBx® System. 146 patients with pure DCIS received X-ray based IORT therapy using the Xoft® Axxent eBx® System at Hoag Memorial Hospital Presbyterian between June 2010 to April 2016 and were accrued to an IORT data registry study. The protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. Acute complications were observed in 18% of patients and included hematomas that required drainage, an infection treated with antibiotics, and erythema. Chronic complications were observed in 12% of patients and included a seroma, fibrosis and hyperpigmentation. The majority of acute and chronic problems were mild (Grade I). If Grade I erythema, fibrosis, and hyperpigmentation are not included, only 11/146 patients (7.5%) had significant complications. The rate of acute and chronic complications from X-ray IORT in DCIS patients was low compared to historical toxicity rates observed in DCIS patients treated with whole breast irradiation. Our data indicate that X-ray IORT can be utilized safely in patients diagnosed with DCIS.

Acute and Chronic Complications in Breast Cancer Patients Treated with Intraoperative Radiation Therapy.

INTRODUCTION: Intraoperative radiation therapy (IORT) permits the delivery of radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available about the complications associated with this modality of treatment using the Xoft(®) Axxent Electronic Brachytherapy (Axxent) System. METHODS: A total of 702 patients who received IORT using the Xoft(®) Axxent System at Hoag Memorial Hospital Presbyterian between June 2010-February 2016 were accrued in an IORT data registry study. The prospective and retrospective protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 3 months, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. RESULTS: Acute complications were observed in 21 % of patients and included hematomas that required drainage, seromas requiring drainage more than 3 times, infections treated with antibiotics or surgery, necrosis requiring surgery, and erythema. Chronic complications were observed in 13 % of patients and included seromas, fibrosis, and hyperpigmentation. The majority of acute and chronic problems from IORT were mild. If grade I erythema, fibrosis, and hyperpigmentation were removed, only 32 of 702 (4.6 %) had significant complications. Our complication rates were comparable to those of the TARGIT trial. CONCLUSIONS: IORT is a modality that safely delivers radiation therapy to patients diagnosed with breast cancer. This technique allows women who cannot (or decline to) undergo whole breast radiation to consider breast-conserving therapy rather than mastectomy.

Durable complete response of refractory, progressing metastatic melanoma after treatment with a patient-specific vaccine.

A patient with metastatic melanoma who experienced a durable complete response after treatment with a patient-specific vaccine has been described in this article. This 59-year-old woman presented with cervical spine metastases and, within the year, had experienced local disease progression and, despite various therapies, metastases to the axilla, rectum, gall bladder, and multiple soft-tissue sites. She had previously received radiation therapy, combination chemotherapy, interleukin-2 plus interferon biotherapy, and gamma knife radiosurgery, and undergone multiple surgical resections. At the time vaccine therapy was initiated, she had multiple, new, measurable, soft-tissue metastases that were increasing in size. She was treated with a vaccine consisting of autologous dendritic cells incubated with irradiated tumor cells from an autologous tumor cell line and suspended in granulocyte-macrophage colony stimulating factor (GM-CSF), with subcutaneous injections once a week for 3 weeks and monthly for 5 months. There was evidence of disease regression by the completion of therapy. A few months later a complete response was documented by radiologic scans, and subsequently reconfirmed at 6-month intervals. She remains in complete remission >2.5 years after starting the vaccine, and >2 years after completing the vaccine, and survives >4 years after her initial presentation with bone, bowel, and lymph node metastases. This is the first time she has been in a complete remission since her initial diagnosis. Patient-specific vaccines can sometimes induce durable complete regression of progressing soft-tissue melanoma metastases.

Nitrofen inhibition of pulmonary growth and development occurs in the early embryonic mouse.

BACKGROUND/PURPOSE: It was believed previously that pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) was a consequence of the herniation of abdominal viscera into the chest. Using the murine nitrofen-induced model of CDH, the authors evaluated lung growth and development before diaphragm closure or herniation. METHODS: The authors examined nitrofen-exposed early embryonic lungs on embryonic day 12 (E12). Branching morphogenesis was quantified before and after 4 days in culture in serumless chemically defined media and compared with age-matched control lungs. The mRNA expression of proliferative and developmental markers in cultured lungs was then determined. RESULTS: Nitrofen-exposed lungs had 30% fewer total terminal branches than age-matched controls (9.3 +/- 1.9 nitrofen v 13.7 +/- 2.6 control; P <.001). Hypoplasia also was more profound in the left than the right lung. These effects persisted after culturing the lungs for 4 days in serumless chemically-defined media (31.7 +/- 6.8 nitrofen v 42.9 +/- 8.4 control, P <.001). Furthermore, the mRNA expression of proliferative and developmental markers was decreased in nitrofen-exposed E12 lungs cultured for 4 days (as a percentage of age-matched controls): cyclin A (69.28%; P =.04), Nkx2.1 (44.4%, 0.04), SP-A (24.1%; P =.008), SP-B (23.4%; P =.05), SP-C (20%; P =.06), and CC-10 (13.8%; P =.04). CONCLUSION: Nitrofen induces primary pulmonary hypoplasia and immaturity in the early embryonic mouse, and this effect persists in culture.