M. Bolla

Conformal external radiotherapy of prostatic carcinoma: requirements and experimental results

The aim of conformal radiotherapy is to deliver, with high precision, a specific dose (which may be a high dose) to a planning target volume, concurrently with irradiating as little as possible healthy tissue and organs at risk. Radiation therapy may suffer from a number of problems that result in both over- or under-sizing the irradiation fields, making over-rough simplifications of the irradiation ballistics and delivering an insufficient tumoral dose (to spare critical organs and reduce toxicity). One of these problems lies in the accurate positioning of the planning target volume with respect to the irradiation system, thence in the correct execution of the ballistics. In this paper, we describe a system aiming at achieving a higher overall accuracy in the delivery of prostatic boost for carcinoma of the prostate. The system is based on the use of ultrasonic images for measuring the actual position of the prostate just before irradiation. Since these images are registered with pre-operative (CT or MR) images, the position and orientation of the planning target volume is computed with respect to the irradiation system, and can be corrected accordingly. First experiments have been performed on dummies, and the results are discussed.

Quality assurance of the EORTC radiotherapy trial 22863 for prostatic cancer: the dummy run

The results of a dummy run involving nine centers participating in a study comparing radiotherapy alone with radiotherapy plus hormone therapy in patients with high metastatic risk prostatic cancer (EORTC protocol 22863) show that, in all centers but one, patients are treated in the same way. However, they have also indicated that protocol compliance could be improved by a better assessment of the target volume, by taking into account of the use of protective shields and of variations in radiological density, by determining beam position on a large number of slices, and by the use of CT scan images for treatment planning.

MRI/TRUS data fusion for brachytherapy.

Prostate brachytherapy consists in placing radioactive seeds for tumour destruction under transrectal ultrasound imaging (TRUS) control. It requires prostate delineation from the images for dose planning. Because ultrasound imaging is patient‐ and operator‐dependent, we have proposed to fuse MRI data to TRUS data to make image processing more reliable. The technical accuracy of this approach has already been evaluated.

Development of a Novel Robot for Transperineal Needle Based Interventions: Focal Therapy, Brachytherapy and Prostate Biopsies

PURPOSE We report what is to our knowledge the initial experience with a new 3-dimensional ultrasound robotic system for prostate brachytherapy assistance, focal therapy and prostate biopsies. Its ability to track prostate motion intraoperatively allows it to manage motions and guide needles to predefined targets. MATERIALS AND METHODS A robotic system was created for transrectal ultrasound guided needle implantation combined with intraoperative prostate tracking. Experiments were done on 90 targets embedded in a total of 9 mobile, deformable, synthetic prostate phantoms. Experiments involved trying to insert glass beads as close as possible to targets in multimodal anthropomorphic imaging phantoms. Results were measured by segmenting the inserted beads in computerized tomography volumes of the phantoms. RESULTS The robot reached the chosen targets in phantoms with a median accuracy of 2.73 mm and a median prostate motion of 5.46 mm. Accuracy was better at the apex than at the base (2.28 vs 3.83 mm, p <0.001), and similar for horizontal and angled needle inclinations (2.7 vs 2.82 mm, p = 0.18). CONCLUSIONS To our knowledge this robot for prostate focal therapy, brachytherapy and targeted prostate biopsies is the first system to use intraoperative prostate motion tracking to guide needles into the prostate. Preliminary experiments show its ability to reach targets despite prostate motion.

Sequential combination of 5-fluorouracil, cis-platinum and irradiation in unresectable non-small cell lung cancer

Twenty patients with unresectable non-small cell lung carcinoma, 15 stage III and 5 stage IV (supraclavicular lymphadenopathy) were treated with a combination of three courses of chemotherapy and hypofractionated irradiation followed after 3 weeks by split-course radiotherapy. Each course was repeated every 3 weeks with the following sequence. Cis-platin (CDDP) (20 mg/m2) was given in a 20-min infusion, followed by a 2-h infusion of 5-fluorouracil (5-FU) (400 mg/m2) on days 1, 2, 5 and 6. Radiation with a dose of 3 Gy on the target volume was given on days 3 and 4, after a 2-h infusion of 5-FU (400 mg/m2). Split course of irradiation consisted of 16 Gy in 5 fractions repeated after 3 weeks interval. The objective response rate was 75%. Median follow-up was 24 months, the median survival was 14 months. The 1-year survival was 53% and the 2-year survival was 16%.

The Potential Impact of Adjuvant Radiation Therapy on Urinary Continence Recovery After Radical Prostatectomy

Recent publications from the Department of Urology at Vita-Salute University were devoted to the positive impact of adjuvant radiotherapy (aRT) after pelvic lymphadenectomy and radical prostatectomy (RP) for prostate cancer [1,2]. A new publication shed light on the potential detrimental effect of aRT on urinary continence (UC) in a series of 361 contemporary patients classified with pT2 R1 or pT3a/pT3b node-negative disease with unfavourable pathologic characteristics [3]. Such a statement may make urologists and patients ambivalent towards the value of aRT and justifies a critical analysis. Urologists do not want to face complaints from patients after aRT, particularly if the indication for aRT was questionable, and patients want to enjoy not only a cancer-free status but also a life free of physical and psychological health problems related to cancer and/or its treatment. In the Milan series [1,2], aRT was not assigned randomly, making the interaction of treatment exposure and patient characteristics likely, and the two cohorts harboured significant differences unfavourable to aRT with regard to age, pathologic stage, Gleason score, Cancer of the Prostate Risk Assessment (CAPRA) score used as a proxy for disease severity, and bilateral nerve-sparing approach. Other parameters were missing but also could be unfavourable to aRT: (1) the breakdown of the surgical margin positivity for pT3a-b stage; (2) the percentage of patients not achieving undetectable prostate-specific antigen (PSA); and (3) UC status at the delivery of aRT, of paramount importance because incontinence contraindicates aRT unless the patient has grade 1 urinary incontinence (coughing, sneezing). With a mean follow-up of 30 mo, the Milan series did not display late toxicity analysis but rather 3-yr UC recovery of 59% for patients submitted to aRT

Prognostic factors of second primary contralateral breast cancer in early‑stage breast cancer

The aim of the present study was to investigate the therapeutic outcome of early-stage breast cancer (pT1aN0M0) and to identify prognostic factors for secondary primary contralateral breast cancer (CBC). A total of 85 patients with mammary carcinomas were included. All patients had undergone breast surgery and adjuvant treatment between January 2001 and December 2008 at the Central Hospital of Grenoble University (Grenoble, France). The primary end-points were disease-free survival and secondary CBC, and the potential prognostic factors were investigated. During a median follow-up of 60 months, 10 of the 85 patients presented with secondary primary cancer, of which six suffered with CBC. No patient mortalities were reported. The rates of CBC were 2.35, 3.53 and 7.06% at one, two and five years, respectively. The cumulative univariate analysis showed that microinvasion and family history are potential risk factors for newly CBC. The current study also demonstrated that secondary CBC was more likely to occur in patients with microinvasion or a family history of hte dise. In addition, the systematic treatment of secondary CBC should include hormone therapy.

Adjuvant or Immediate External Irradiation After Radical Prostatectomy with Pelvic Lymph Node Dissection for High-Risk Prostate Cancer: A Multidisciplinary Decision

Abdollah et al. [1] selected, from a cohort of 6357 patients who underwent radical prostatectomy with extended pelvic lymph node dissection in the same institution between 1988 and 2008, a series of 1049 patients with pathologically advanced prostate cancer (PCa). The aim was to evaluate the impact of risk prognostic factors on survival with a regression analysis, and then to evaluate the relationship between adjuvant radiotherapy (ART) and survival according to the number of selected risk factors. The adjuvant treatments

Combination of 5-FU Cisplatinum and hypofractionated irradiation followed by split-course radiotherapy in 47 patients with unresectable non small cell lung cancer

Forty-seven patients with unresectable non small cell lung carcinoma, 15 stage IIIA, 31 stage IIIB, 1 stage IV (cervical lymphadenopathy) were treated with a combination of three courses of chemotherapy and hypofractionated irradiation followed after 3 weeks by split course radiotherapy. Each course was repeated every 3 weeks with the following sequence: Cisplatinum (CDDP) (20 mg/m2) was given in a 20-min infusion, followed by a 2-h infusion of 5-fluorouracil (5-FU) (400 mg/m2) on days 1, 2, 5 and 6. Radiation with a dose of 3 Gy on the target volume was given on days 3 and 4--in one fraction for the former 27 patients, in 2 fractions of 1.5 Gy for the latter 20 patients with a 6-h interval--after a 2-h infusion of 5-FU (400 mg/m2). The results remain disappointing: the objective response rate was 53%, the median survival was 10 months for the series, and the one-year survival 47%. The median survival was 14 months for IIIA, 10 months for IIIB and IV. Regarding the therapeutic regimen there seems to be less morbidity with 2 fractions per day for which the median survival is nearly the same at 10 months (1 fraction/day) versus 12 months (2 fractions/day).

Apport de l’association radiothérapie externe-hormonothérapie dans le traitement du cancer de la prostate à haut risque

Treatment of high-risk prostate cancer - localized or locally advanced - is based on the combination of external irradiation and hormonal treatment by LHRH analogue (aLHRH) according to the results of phases III randomized trials RTOG and/or EORTC trials. These trials show a significant improvement of overall or specific survival. Localized prostate cancer require 6-month complete androgen blockade, while locally advanced prostate cancer need a long-term hormonal treatment for a duration ranging from 2,5 to 3 years. Some trials, which have a long follow-up show that the risk of cardiovascular death is not significantly increased by hormonal treatment.