Electron Beam Intraoperative Radiotherapy (ELIOT) in Pregnant Women with Breast Cancer: From in Vivo Dosimetry to Clinical Practice.

BACKGROUND: The aim of this study was to confirm our preliminary results with in vivo dosimetry in non-pregnant breast cancer patients receiving electron beam intraoperative radiotherapy (ELIOT) and to report on the first treatment in a pregnant woman. PATIENTS AND METHODS: Following our previous experience, 5 non-pregnant patients receiving ELIOT to the tumor bed after breast-conserving surgery (BCS) were studied with thermoluminescent dosimeters positioned in the subdiaphragmatic region, within the uterus, and in the ovarian region. In December 2011, the first pregnant breast cancer patient underwent BCS and ELIOT (21 Gy at 90% isodose) during the 15th week of gestation. RESULTS: The mean dose to the subdiaphragmatic external region in the 5 non-pregnant patients was 5.57 mGy, while pelvic measurements were below 1 mGy. The actual dosimetry of the pregnant patient showed a mean subdiaphragmatic dose of 4.34 mGy, a mean suprapubic dose of 1.64 mGy, and mean ovarian doses of 1.48 mGy (right-sided) and 1.44 mGy (left-sided). The expected dose to the fetus was estimated as 0.84 mGy (0.004% of the prescribed dose). CONCLUSION: ELIOT as an anticipated boost to the breast could be considered in pregnant women in the early second trimester, postponing whole-breast irradiation after delivery.

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).

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 cm(3) (range: 12.7-44.4 cm(3)) and 8.6 cm(3) (range: 3.6-17.1 cm(3)), 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 cm(3) 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.

Radiotherapy in Prostate Cancer Patients With Pelvic Lymphocele After Surgery: Clinical and Dosimetric Data of 30 Patients.

INTRODUCTION: The purpose of the study was to evaluate the feasibility of irradiation after prostatectomy in the presence of asymptomatic pelvic lymphocele. PATIENTS AND METHODS: The inclusion criteria for this study were: (1) patients referred for postoperative (adjuvant or salvage) intensity modulated radiotherapy (IMRT; 66-69 Gy in 30 fractions); (2) detection of postoperative pelvic lymphocele at the simulation computed tomography [CT] scan; (3) no clinical symptoms; and (4) written informed consent. Radiotherapy toxicity and occurrence of symptoms or complications of lymphocele were analyzed. Dosimetric data (IMRT plans) and the modification of lymphocele volume during radiotherapy (cone beam CT [CBCT] scan) were evaluated. RESULTS: Between January 2011 and July 2013, in 30 of 308 patients (10%) treated with radiotherapy after prostatectomy, pelvic lymphocele was detected on the simulation CT. The median lymphocele volume was 47 cm(3) (range, 6-467.3 cm(3)). Lymphocele was not included in planning target volume (PTV) in 8 cases (27%). Maximum dose to lymphocele was 57 Gy (range, 5.7-73.3 Gy). Radiotherapy was well tolerated. In all but 2 patients, lymphoceles remained asymptomatic. Lymphocele drainage-because of symptom occurrence-had to be performed in 2 patients during IMRT and in one patient, 7 weeks after IMRT. CBCT at the end of IMRT showed reduction in lymphocele volume and position compared with the initial data (median reduction of 37%), more pronounced in lymphoceles included in PTV. CONCLUSION: Radiotherapy after prostatectomy in the presence of pelvic asymptomatic lymphocele is feasible with acceptable acute and late toxicity. The volume of lymphoceles decreased during radiotherapy and this phenomenon might require intermediate radiotherapy plan evaluation.

The role of [(18)F]FDG-PET/CT in staging and treatment planning for volumetric modulated Rapidarc radiotherapy in cervical cancer: experience of the European Institute of Oncology, Milan, Italy.

RATIONALE: to evaluate the role of 18F-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) integrated with computer tomography (CT) scan [(18)F]FDG-PET/CT in the staging and target volume definition in Intensity Modulated RapidarcTM Delivery (RA-IMRT) in cervical cancer. METHODS: From June 2010 to December 2011, 66 patients affected by cervical cancer, candidates for definitive or adjuvant radiochemotherapy, underwent standard staging with CT and magnetic resonance imaging (MRI). All patients underwent [(18)F]FDG-PET/CT in order to exclude distant metastases and to define gross tumor volume (GTV). 40 and 26 patients received exclusive and adjuvant radiotherapy, respectively. RA-IMRT with simultaneous integrated boost (SIB) to the positive disease technique was employed. RESULTS: [(18)F]FDG-PET/CT has changed the stage, and radiotherapy treatment planning was modified in 25% and 7.7 % of patients that received definitive and adjuvant radiotherapy, respectively. Particularly [(18)F]FDG-PET/CT imaging showed metabolically active tumor in lymph nodes area, therefore the stage and the treatment planning changed for these patients. CONCLUSIONS: [(18)F]FDG-PET/CT leads to a better staging and definition of disease and has the potential of showing lymph-node metastasis not only within the pelvis but also in the para-aortic area. In addition, [(18)F]FDG-PET/CT is useful for better definition of the target volume and to produce a 'dose painted' treatment. This might also open the field for escalation dose regimens.

The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO--Young Members Working Group (AIRO Giovani).

Stereotactic ablative radiotherapy is a modern cancer treatment strategy able to deliver highly focused radiation in one or a few fractions with a radical intent in several clinical settings. Young radiation oncologists need a constant and tailored update in this context to improve patient care in daily clinical practice. A recent meeting of AIRO Giovani (AIRO--Young Members Working Group) was specifically addressed to this topic, presenting state-of-the-art knowledge, based on the latest evidence in this field. Highlights of the congress are summarized and presented in this report, including thorough contributions of the speakers dealing with the role of stereotactic ablative radiotherapy in both oncological and non-oncological diseases, divided according to anatomical and clinical scenarios: intra-cranial settings (brain malignant primary tumors, metastases, benign tumors and functional disorders) and extra-cranial indications (lung primary tumors and metastases, thoracic re-irradiation, liver, lymph node and bone metastases, prostate cancer). With literature data discussed during the congress as a background, stereotactic ablative radiotherapy has proved to be a consolidated treatment approach in specific oncological and non-oncological scenarios, as well as a promising option in other clinical settings, requiring a further prospective validation in the near future. We herein present an updated overview of stereotactic ablative radiotherapy use in the clinic.

Gynecologic tumors: how to communicate imaging results to the surgeon.

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.

Second malignancies following breast cancer treatment: a case-control study based on the Peridose methodology. Allegro project (task 5.4).

AIMS AND BACKGROUND: To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. MATERIAL AND STUDY DESIGN: A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose. RESULTS: 195 second cancers were registered (19% [corrected] of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was -3.15 cGy (range, -15.8 cGy and +2.7 cGy). CONCLUSIONS: The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.

Combined 18F-FDG-PET/CT imaging in radiotherapy target delineation for head-and-neck cancer.

PURPOSE: To evaluate the effect of the use of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in radiotherapy target delineation for head-and-neck cancer compared with CT alone. METHODS AND MATERIALS: A total of 38 consecutive patients with head-and-neck cancer were included in this study. The primary tumor sites were as follow: 20 oropharyngeal tumors, 4 laryngeal tumors, 2 hypopharyngeal tumors, 2 paranasal sinuses tumors, 9 nasopharyngeal tumors, and 1 parotid gland tumor. The FDG-PET and CT scans were performed with a dedicated PET/CT scanner in one session and then fused. Subsequently, patients underwent treatment planning CT with intravenous contrast enhancement. The radiation oncologist defined all gross tumor volumes (GTVs) using both the PET/CT and CT scans. RESULTS: In 35 (92%) of 38 cases, the CT-based GTVs were larger than the PET/CT-based GTVs. The average total GTV from the CT and PET/CT scans was 34.54 cm(3) (range, 3.56-109) and 29.38 cm(3) (range, 2.87-95.02), respectively (p < 0.05). Separate analyses of the difference between the CT- and PET/CT-based GTVs of the primary tumor compared with the GTVs of nodal disease were not statistically significant. The comparison between the PET/CT-based and CT-based boost planning target volumes did not show a statistically significant difference. All patients were alive at the end of the follow-up period (range, 3-38 months). CONCLUSION: GTVs, but not planning target volumes, were significantly changed by the implementation of combined PET/CT. Large multicenter studies are needed to ascertain whether combined PET/CT in target delineation can influence the main clinical outcomes.