Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.     

Pathogenic BRCA1 mutations may be necessary but not sufficient for tissue genomic heterogeneity: Deep sequencing data from ovarian cancer patients

Background

Tissue genomic heterogeneity (t-HET) in patients with epithelial ovarian cancer (OVCA) is related to tissue plasticity, i.e., flexibility to adapt to adverse molecular environments. Here, we interrogated the presence and clinical relevance of OVCA t-HET.

Comparison of quality of life and arm complaints after axillary lymph node dissection vs sentinel lymph node biopsy in breast cancer patients

The sentinel lymph node biopsy (SLNB) represents a minimal invasive surgical method for axillary staging in patients with primary breast cancer. In a prospective study, evaluation of quality of life (QOL) and arm morbidity was performed before surgery on a total of 56 breast cancer patients. The EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires were used for QOL assessment. Assessment of pain was additionally observed using the McGill Pain Questionnaire. Arm mobility was observed by goniometric measurement of arm movement. Data were collected before surgery (t1), 1 week after discharge (t2) and 9-12 months after surgery (t3).The type of axillary surgery does not seem to affect global QOL at a short-time follow-up, but patients recover sooner after SLNB. Body image and sexual functioning remain stable in both types of axillary surgery. Arm/shoulder pain was reported in 36% of patients after SLNB in comparison to 68% receiving axillary lymph node dissection (ALND), and 'numbness' was reported only in 4% of patients in the SLNB group vs 19.3% after ALND. Abduction, flexion and horizontal adduction of the affected arm show significant impairment after ALND. Breast cancer patients should be counselled about the benefits of SLNB over ALND concerning QOL and postsurgery side effects in a short-term follow-up.     

Neural stem/progenitor cells differentiate into oligodendrocytes,reduce inflammation,and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury

The central nervous system has limited capacity for regeneration after traumatic injury. Transplantation of neural stem/progenitor cells (NPCs) has been proposed as a potential therapeutic approach while insulin‐like growth factor I (IGF‐I) has neuroprotective properties following various experimental insults to the nervous system. We have previously shown that NPCs transduced with a lentiviral vector for IGF‐I overexpression have an enhanced ability to give rise to neurons in vitro but also in vivo, upon transplantation in a mouse model of temporal lobe epilepsy. Here we studied the regenerative potential of NPCs, IGF‐I‐transduced or not, in a mouse model of hippocampal mechanical injury. NPC transplantation, with or without IGF‐I transduction, rescued the injury‐induced spatial learning deficits as revealed in the Morris Water Maze. Moreover, it had beneficial effects on the host tissue by reducing astroglial activation and microglial/macrophage accumulation while enhancing generation of endogenous oligodendrocyte precursor cells. One or two months after transplantation the grafted NPCs had migrated towards the lesion site and in the neighboring myelin‐rich regions. Transplanted cells differentiated toward the oligodendroglial, but not the neuronal or astrocytic lineages, expressing the early and late oligodendrocyte markers NG2, Olig2, and CNPase. The newly generated oligodendrocytes reached maturity and formed myelin internodes. Our current and previous observations illustrate the high plasticity of transplanted NPCs which can acquire injury‐dependent phenotypes within the host CNS, supporting the fact that reciprocal interactions between transplanted cells and the host tissue are an important factor to be considered when designing prospective cell‐based therapies for CNS degenerative conditions. GLIA 2016;64:763–779     

Local Recurrence Rates in Breast Cancer Patients Treated with Intraoperative Electron-Boost Radiotherapy Versus Postoperative External-Beam Electron-Boost Irradiation

BACKGROUND AND PURPOSE: The purpose of this sequential intervention study was to determine the rate of local recurrences and the rate of distant metastases in patients with invasive breast cancer who had been treated with breast-conserving surgery and postoperative radiation therapy to the whole breast either with postoperative electron boost in group 1 or with intraoperative electron boost (IORT) in group 2. PATIENTS AND METHODS: After breast-conserving surgery, 378 women with invasive breast cancer of tumor sizes T1 and T2 received 51-56.1 Gy of postoperative radiation therapy to the whole breast in 1.7-Gy fractions. 188 of those patients additionally received a postoperative electron boost of 12 Gy in group 1 from January 1996 to October 1998. Consecutively, from October 1998 to March 2001, 190 patients received intraoperative electron-boost radiotherapy of 9 Gy to the tumor bed in group 2. The groups were comparable with regard to age, menopausal status, tumor size, grading, and nodal status. All statistical tests were two-sided. RESULTS: During a median follow-up period of 55.3 months in group 1 and 25.8 months in group 2, local recurrences were observed in eight of 188 patients (4.3%) in group 1, and no local recurrence was seen in group 2 (p=0.082). Distant metastases occurred in 15 of the 188 patients (7.9%) in group 1 and in two of the 190 patients (1.1%) in group 2 (p=0.09). The 4-year actuarial rates of local recurrence were 4.3% (95% confidence interval, 1.8-8.2%) and 0.0% (95% confidence interval, 0.0-1.9%) and the 4-year actuarial rates of distant metastases were 7.9% (95% confidence interval, 4.5-12.8%) and 1.1% (95% confidence interval, 0.1-3.8%). CONCLUSION: Immediate IORT boost yielded excellent local control figures in this prospective investigation and appears to be superior to conventional postoperative boost in a short-term follow-up.     

Extracapsular Extension in Positive Axillary Lymph Nodes in Female Breast Cancer Patients

BACKGROUND AND PURPOSE: There has been little information regarding lymph node-positive breast cancer patients with extracapsular extension (ECE). The aim of this study was to evaluate the role of ECE in predicting survival and relapse rates. PATIENTS AND METHODS: From 1994-2002, 1,078 lymph node-positive women with breast carcinoma were treated at our institution, whereas 301 patients (27.9%) presented with ECE. 91 patients (30.2%) were identified as having three or less lymph nodes involved, 27.9% patients four to six, 15.6% patients seven to nine, and 26.2% patients ten or more nodes, respectively. The median age was 58.4 years (range: 28-84 years) and the median follow-up 34 months (range: 2-99 months). Nodal irradiation was given to patients with four or more positive lymph nodes. Chemotherapy was administered to 69.8%, hormonal therapy to 53.2%, and combined systemic treatment to 26% of patients. RESULTS: The 1-, 3-, and 5-year overall survival (OS) was 98%, 84%, and 73%, the 1-, 3-, and 5-year disease-free survival (DFS) 95%, 69%, and 58%, and the 1-, 3-, and 5-year metastasis-free survival (MFS) 96%, 73%, and 60%. The relapse rates were 6.6% (local), 0.3% (supraclavicular), 0.7% (isolated axillary), 1% (local + axillary), and 0.7% (local + supraclavicular), respectively. 81 patients (27%) developed distant metastases. In December 2002, 245 patients (81.4%) were alive, 202/245 without progression, 32/245 with distant metastases, 5/245 with local/locoregional recurrence, and 6/245 patients with local and distant failure. CONCLUSION: Isolated axillary nodal failure remains low in lymph node-positive patients with ECE. Balancing the risks and benefits of irradiation, we continue to recommend that complete axillary irradiation is not routinely indicated after adequate axillary dissection.     

IOERT as anticipated tumor bed boost during breast‐conserving surgery after neoadjuvant chemotherapy in locally advanced breast cancer—Results of a case series after 5‐year follow‐up

To evaluate retrospectively rates of local (LCR) and locoregional tumor control (LRCR) in patients with locally advanced breast cancer (LABC) who were treated with preoperative chemotherapy (primary systemic treatment, PST) followed by breast‐conserving surgery (BCS) and either intraoperative radiotherapy with electrons (IOERT) preceding whole‐breast irradiation (WBI) (Group 1) or with WBI followed by an external tumor bed boost (electrons or photons) instead of IOERT (Group 2). From 2002 to 2007, 83 patients with clinical Stage II or III breast cancer were enrolled in Group 1 and 26 in Group 2. All patients received PST followed by BCS and axillary lymph node dissection. IOERT boosts were applied by single doses of 9 Gy (90% reference isodose) versus external boosts of 12 Gy (median dose range, 6–16) in 2 Gy/fraction (ICRU). WBI in both groups was performed up to total doses of 51–57 Gy (1.7–1.8 Gy/fraction). The respective median follow‐up times for Groups 1 and 2 amount 59 months (range, 3–115) and 67.5 months (range, 13–120). Corresponding 6‐year rates for LCR, LRCR, metastasis‐free survival, disease‐specific survival and overall survival were 98.5, 97.2, 84.7, 89.2 and 86.4% for Group 1 and 88.1, 88.1, 74, 92 and 92% for Group 2, respectively, without any statistical significances. IOERT as boost modality during BCS in LABC after PST shows a trend to be superior in terms of LCR and LRCR in comparison with conventional boosts.