Roberta Lazzari

Full-Dose Intraoperative Radiotherapy With Electrons During Breast-Conserving Surgery: Experience With 590 Cases

Background:Previous studies show that local recurrences after breast-conserving treatment occur in the site of the primary tumor. The need for postoperative radiotherapy on the whole breast is challenged in favor of radiotherapy limited to the area of the breast at high risk of recurrence. The new mobile linear accelerators easily moved close to the operating table to allow the full-dose irradiation during surgery. Patients and Methods:From July 1999 to December 2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by intraoperative radiotherapy with electrons (ELIOT). Most patients received 21 Gy intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. Results:After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19 patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which resolved within 24 months. Three patients (0.5%) developed local recurrences, 3 patients ipsilateral carcinomas in other quadrants and other 5 patients contralateral breast carcinoma. One patient (0.2%) died of distant metastases. Conclusions:ELIOT is a safe method for treating conservatively operated breasts, avoids the long period of postoperative radiotherapy, and reduces drastically the cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs. Results on short-term and middle-term toxicity up to 5 years of follow-up are good. Data on local control are encouraging.

Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer.

Local recurrences after breast-conserving surgery occur mostly in the quadrant harbouring primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area while irradiation of the whole breast may be avoided. We have developed a new technique of intraoperative radiotherapy of a breast quadrant after the removal of the primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Different dose levels were tested from 10 to 21 Gy without important side effects. A randomized trial is currently ongoing in order to compare conventional irradiation and ELIOT. More than 400 patients have been enrolled. In addition a new approach for nipple and areola complex conservation, including ELIOT, is under investigation.

How Do the ASTRO Consensus Statement Guidelines for the Application of Accelerated Partial Breast Irradiation Fit Intraoperative Radiotherapy? A Retrospective Analysis of Patients Treated at the European Institute of Oncology

PURPOSE To verify how the classification according to the American Society for Therapeutic Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) fits patients treated with intraoperative radiotherapy with electrons (ELIOT) at a single institution. METHODS AND MATERIALS The study included 1,822 patients treated with ELIOT as the sole radiation modality outside of a clinical trial at the European Institute of Oncology after breast-conserving surgery for invasive breast cancer, who were classified into CS groups of suitable, cautionary, and unsuitable. The outcome in terms of ipsilateral breast recurrence, regional node relapse, distant metastases, progression free-survival, cause-specific survival, and overall survival were assessed. RESULTS All the 1,822 cases except for 25 could be classified according to ASTRO CS: 294 patients met the criteria for inclusion into the suitable group, 691 patients into the cautionary group, and 812 patients into the unsuitable group. The 5-year rate of ipsilateral breast recurrence for suitable, cautionary, and unsuitable groups were 1.5%, 4.4%, and 8.8%, respectively (p = 0.0003). Whereas the regional node relapse showed no difference, the rate of distant metastases was significantly different in the unsuitable group compared with the suitable and cautionary groups, having a significant impact on survival. CONCLUSION In the context of patients treated with ELIOT, the ASTRO guidelines identify well the groups for whom APBI might be considered as an effective alternative to whole breast radiotherapy and also identify groups for whom APBI is not indicated.

A new option for early breast cancer patients previously irradiated for Hodgkin's disease: intraoperative radiotherapy with electrons (ELIOT)

IntroductionPatients who have undergone mantle radiotherapy for Hodgkins disease (HD) are at increased risk of developing breast cancer. In such patients, breast conserving surgery (BCS) followed by breast irradiation is generally considered contraindicated owing to the high cumulative radiation dose. Mastectomy is therefore recommended as the first option treatment in these women.MethodsSix patients affected by early breast cancer previously treated with mantle radiation for HD underwent BCS associated with full-dose intraoperative radiotherapy with electrons (ELIOT).ResultsA total dose of 21 Gy (prescribed at 90% isodose) in five cases and 17 Gy (at 100% isodose) in one case were delivered directly to the mammary gland without acute complications and with good cosmetic results. After an average of 30.8 months of follow up, no late sequelae were observed and the patients are free of disease.ConclusionIn patients previously irradiated for HD, ELIOT can avoid repeat irradiation of the whole breast, permit BCS and decrease the number of avoidable mastectomies.

Long-term side effects and cosmetic outcome in a pool of breast cancer patients treated with intraoperative radiotherapy with electrons as sole treatment

AIMS To evaluate late toxicity and cosmetic outcome after intraoperative radiotherapy using electrons (ELIOT) as sole treatment modality in early breast cancer patients. METHODS A total of 119 patients selected randomly among 1200 cases was analyzed. Late toxicities were documented using the LENT-SOMA scoring system, cosmesis was evaluated with the Harvard scale, and a numeric rating scale was used to assess symptoms. RESULTS After a median follow-up of 71 months, grade II fibrosis was observed in 38 patients (31.9%) and grade III fibrosis in 7 patients (5.9%). Postoperative complications (12.6%) did not correlate with late toxicity. Physicians and patients scored cosmesis as excellent or good in 84% and 77.3% of the cases, respectively. Patient satisfaction was higher than 90%. CONCLUSIONS In the study, ELIOT gives low and acceptable long-term toxicity. A longer follow-up and a larger number of patients are needed to confirm these promising results.

Effect of resection and outcome in patients with retroperitoneal sarcoma.

Background:  A consecutive series of 47 patients with retroperitoneal sarcoma (RPS) were resected and prospectively followed.

Kinetic Models for Predicting Cervical Cancer Response to Radiation Therapy on Individual Basis Using Tumor Regression Measured In Vivo With Volumetric Imaging

This article describes a macroscopic mathematical modeling approach to capture the interplay between solid tumor evolution and cell damage during radiotherapy. Volume regression profiles of 15 patients with uterine cervical cancer were reconstructed from serial cone-beam computed tomography data sets, acquired for image-guided radiotherapy, and used for model parameter learning by means of a genetic-based optimization. Patients, diagnosed with either squamous cell carcinoma or adenocarcinoma, underwent different treatment modalities (image-guided radiotherapy and image-guided chemo-radiotherapy). The mean volume at the beginning of radiotherapy and the end of radiotherapy was on average 23.7 cm3 (range: 12.7-44.4 cm3) and 8.6 cm3 (range: 3.6-17.1 cm3), respectively. Two different tumor dynamics were taken into account in the model: the viable (active) and the necrotic cancer cells. However, according to the results of a preliminary volume regression analysis, we assumed a short dead cell resolving time and the model was simplified to the active tumor volume. Model learning was performed both on the complete patient cohort (cohort-based model learning) and on each single patient (patient-specific model learning). The fitting results (mean error: ∼16% and ∼6% for the cohort-based model and patient-specific model, respectively) highlighted the model ability to quantitatively reproduce tumor regression. Volume prediction errors of about 18% on average were obtained using cohort-based model computed on all but 1 patient at a time (leave-one-out technique). Finally, a sensitivity analysis was performed and the data uncertainty effects evaluated by simulating an average volume perturbation of about 1.5 cm3 obtaining an error increase within 0.2%. In conclusion, we showed that simple time-continuous models can represent tumor regression curves both on a patient cohort and patient-specific basis; this discloses the opportunity in the future to exploit such models to predict how changes in the treatment schedule (number of fractions, doses, intervals among fractions) might affect the tumor regression on an individual basis.

Aggressive Treatment Approach for Cloacogenic Carcinoma of the Anorectum: Report from a Single Cancer Center

Background/Aims: The prognosis of cloacogenic carcinoma of the anorectum has rarely been investigated, and its clinical behavior is supposed to be similar to common squamous anal cancers. During the last 10 years, chemoradiation treatment (CRT) has been considered the standard of care for anal cancer. Methods: We retrospectively investigated the treatment of cloacogenic cancers treated within the framework of a multidisciplinary cancer center team during an 8-year period. The medical records of 7 patients affected by cloacogenic carcinoma were analyzed. Three patients presented distant metastases at the time of diagnosis. CRT using 5-fluorouracil + mitomycin or cisplatin was considered the gold standard for those cases amenable to cure. Results: After a mean follow-up time of 33 months (range 9–100), disease recurrence or progression was observed in 6 patients, which caused death in 3 of them. Three- and 5-year actuarial overall survival rates were 71 and 48%, respectively. Conclusions: Our data seem to suggest that the cloacogenic origin could present prognostic relevance within the wide spectrum of anal cancers. This should be carefully considered when submitting patients to aggressive and prolonged treatments. However, this hypothesis needs to be confirmed by larger series of this disease.

Modeling the Interplay Between Tumor Volume Regression and Oxygenation in Uterine Cervical Cancer During Radiotherapy Treatment

This paper describes a patient-specific mathematical model to predict the evolution of uterine cervical tumors at a macroscopic scale, during fractionated external radiotherapy. The model provides estimates of tumor regrowth and dead-cell reabsorption, incorporating the interplay between tumor regression rate and radiosensitivity, as a function of the tumor oxygenation level. Model parameters were estimated by minimizing the difference between predicted and measured tumor volumes, these latter being obtained from a set of 154 serial cone-beam computed tomography scans acquired on 16 patients along the course of the therapy. The model stratified patients according to two different estimated dynamics of dead-cell removal and to the predicted initial value of the tumor oxygenation. The comparison with a simpler model demonstrated an improvement in fitting properties of this approach (fitting error average value <;5%, p <; 0.01), especially in case of tumor late responses, which can hardly be handled by models entailing a constant radiosensitivity, failing to model changes from initial severe hypoxia to aerobic conditions during the treatment course. The model predictive capabilities suggest the need of clustering patients accounting for cancer cell line, tumor staging, as well as microenvironment conditions (e.g., oxygenation level).

Gynecologic tumors: how to communicate imaging results to the surgeon

Abstract Gynecologic cancers are a leading cause of morbidity and mortality for female patients, with an estimated 88,750 new cancer cases and 29,520 deaths in the United States in 2012. To offer the best treatment options to patients it is important that the radiologist, surgeon, radiation oncologist, and gynecologic oncologist work together with a multidisciplinary approach. Using the available diagnostic imaging modalities, the radiologist must give appropriate information to the surgeon in order to plan the best surgical approach and its timing.