Ten daily fractions for partial breast irradiation. Long-term results of a prospective phase II trial.

Partial breast irradiation (PBI) is an effective adjuvant treatment after breast conservative surgery for selected early-stage breast cancer patients. However, the best fractionation scheme is not well defined. Hereby, we report the 5-year clinical outcome and toxicity of a phase II prospective study of a novel regimen to deliver PBI, which consists in 40 Gy delivered in 10 daily fractions. Patients with early-stage (pT1-pT2, pN0-pN1a, M0) invasive breast cancer were enrolled after conservative surgery. The minimum age at diagnosis was 60 years old. PBI was delivered with 3D-conformal radiotherapy technique with a total dose of 40 Gy, fractionated in 10 daily fractions (4 Gy/fraction). Eighty patients were enrolled. The median follow-up was 67 months. Five-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 95%, 91%, and 96%, respectively. Grade I and II subcutaneous fibrosis were documented in 23% and 5% of cases. No grade III late toxicity was observed. PBI delivered in 40 Gy in 10 daily fractions provided good clinical results and was a valid radiotherapy option for early-stage breast cancer patients.

Prediction of skin dose in low-kV intraoperative radiotherapy using machine learning models trained on results of in vivo dosimetry.

PURPOSE: The purpose of this study was to implement a machine learning model to predict skin dose from targeted intraoperative (TARGIT) treatment resulting in timely adoption of strategies to limit excessive skin dose. METHODS: A total of 283 patients affected by invasive breast carcinoma underwent TARGIT with a prescribed dose of 6 Gy at 1 cm, after lumpectomy. Radiochromic films were used to measure the dose to the skin for each patient. Univariate statistical analysis was performed to identify correlation of physical and patient variables with measured dose. After feature selection of predictors of in vivo skin dose, machine learning models stepwise linear regression (SLR), support vector regression (SVR), ensemble with bagging or boosting, and feed forward neural networks were trained on results of in vivo dosimetry to derive models to predict skin dose. Models were evaluated by tenfold cross validation and ranked according to root mean square error (RMSE) and adjusted correlation coefficient of true vs predicted values (adj-R2 ). RESULTS: The predictors correlated with in vivo dosimetry were the distance of skin from source, depth-dose in water at depth of the applicator in the breast, use of a replacement source, and irradiation time. The best performing model was SVR, which scored RMSE and adj-R2 , equal to 0.746 [95% confidence intervals (CI), 95% CI 0.737,0.756] and 0.481 (95% CI 0.468,0.494), respectively, on the tenfold cross validation. CONCLUSION: The model trained on results of in vivo dosimetry can be used to predict skin dose during setup of patient for TARGIT and this allows for timely adoption of strategies to prevent of excessive skin dose.

Seven fractions to deliver partial breast irradiation: the toxicity is Low.

PURPOSE: To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction). MATERIALS AND METHODS: Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma. RESULTS: Seventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively. CONCLUSIONS: 35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.

Surgery-induced wound response promotes stem-like and tumor-initiating features of breast cancer cells, via STAT3 signaling.

Inflammation is clinically linked to cancer but the mechanisms are not fully understood. Surgery itself elicits a range of inflammatory responses, suggesting that it could represent a perturbing factor in the process of local recurrence and/or metastasis. Post-surgery wound fluids (WF), drained from breast cancer patients, are rich in cytokines and growth factors, stimulate the in vitro growth of breast cancer cells and are potent activators of the STAT transcription factors. We wondered whether STAT signaling was functionally involved in the response of breast cancer cells to post-surgical inflammation. We discovered that WF induced the enrichment of breast cancer cells with stem-like phenotypes, via activation of STAT3. In vitro, WF highly stimulated mammosphere formation and self-renewal of breast cancer cells. In vivo, STAT3 signaling was critical for breast cancer cell tumorigenicity and for the formation of local relapse after surgery. Overall, we demonstrate here that surgery-induced inflammation promotes stem-like phenotypes and tumor-initiating abilities of breast cancer cells. Interfering with STAT3 signaling with a peri-surgical treatment was sufficient to strongly suppress this process. The understanding of the crosstalk between breast tumor-initiating cells and their microenvironment may open the way to successful targeting of these cells in their initial stages of growth and be eventually curative.

Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions.

PURPOSE: To assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction). METHODS AND MATERIALS: Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1-T2 pN0-N1a) invasive ductal carcinoma. RESULTS: 77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged "good/excellent" and "poor" in 75 (97%) and in 2 (3%) patients, respectively. CONCLUSIONS: 40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.

Locoregional failure in early-stage breast cancer patients treated with radical mastectomy and adjuvant systemic therapy: which patients benefit from postmastectomy irradiation?

PURPOSE: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). METHODS AND MATERIALS: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. RESULTS: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. CONCLUSIONS: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

[Follow-up of patients submitted to antireflux laparoscopic treatment. A study by a telephone questionnaire]. / Follow-up dei pazienti sottoposti a chirurgia laparoscopica antireflusso mediante questionario telefonico.

OBJECTIVE: As it is difficult to submit patients to instrumental follow-up after laparoscopic treatment of the gastroesophageal reflux disease (GERD), it is not easy to have a complete patients analysis after fundoplication. Telephone questionnaire can be a valid instrument to investigate clinical outcome and patients satisfaction to surgery. METHODS: This study discusses the results acquired through a telephone questionnaire which has been administered to patients undergoing laparoscopic fundoplication to study postoperative clinical evolution of GERD and satisfaction to surgery through a numerical rating scale from 1 to 10. RESULTS: Sixty three patients, who had a laparoscopic antireflux procedure at Department of General Surgery of the University of Udine (Italy), answered to telephone questionnaires. Fifty patients (74.9%) reported no symptoms. Patients satisfaction to surgery was 7.93 +/- 2.36. Fifty eight patients (92.1%) would have repeated the operation and 59 (93.6%) would have advised it to a friend suffering of GERD. A significant difference of patients satisfaction between preoperative typical and atypical symptoms has been found (8.43 +/- 2.04 vs. 6.95 +/- 2.71 p < 0.05). DISCUSSION AND CONCLUSION: Telephone questionnaire is comparable with face to face consultation, allowing to do a correct clinical follow-up, to exclude patients accusing pathological acid reflux after fundoplication; however preoperative symptoms are not so accurate as postoperative symptoms. Their presence giustifies a postoperative oesophageal pH metry.