[Prevalence of pain in radiotherapy and improvement of its management]. / Prévalence de la douleur en radiothérapie et amélioration de sa prise en charge.

PURPOSE: To assess pain prevalence, its features and its management in a radiotherapy department of a French public general hospital. To highlight strategies to improve pain screening and treatment. METHODS: Designed in conjunction with pain management specialists, a cross-sectional study on pain was carried out. All patients treated in the department being interviewed with a standardised questionnaire during 2 days. RESULTS: Among 91 patients, 63.7% reported pain in daily life. They respectively represented 100%, 85.7% and 83.3% all of the patients treated for brain tumours, for bone metastasis and for head and neck cancers. Only 7.7% of patients reported pain during radiotherapy sessions. Among patients reporting pain, 70.7% received pain relief treatment and 60.8% of them thought this was adequate. While 51.6% of patients knew there was a specialist pain unit in the hospital, only 5.5% were offered a consultation with it. This unit provides non-pharmacological pain management techniques. CONCLUSIONS: This study confirms the importance, the underestimation and undertreatment, of pain management in radiotherapy departments. We recommend using a standardised questionnaire to identify patients at highest risk of pain, and the use of specialised pain relief teams when needed. A radiation therapist could act as a referrer to the pain relief team. Pain management remains teamwork, with links to specialised units.

Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.

BACKGROUND: How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy. METHODS: This open-label, multicentre, phase 3, randomised controlled trial, was done in 43 French study centres. We enrolled men (aged ≥18 years) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate (but no previous androgen deprivation therapy or pelvic radiotherapy), and who had stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0·2 to less than 2·0 µg/L following radical prostatectomy, without evidence of clinical disease. Patients were randomly assigned (1:1) centrally via an interactive web response system to standard salvage radiotherapy (three-dimensional [3D] conformal radiotherapy or intensity modulated radiotherapy, of 66 Gy in 33 fractions 5 days a week for 7 weeks) or radiotherapy plus short-term androgen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later. Randomisation was stratified using a permuted block method according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00423475. FINDINGS: Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% [95% CI 75-84] vs 62% [57-67]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone. The most frequently occuring acute adverse events related to goserelin were hot flushes, sweating, or both (30 [8%] of 366 patients had a grade 2 or worse event; 30 patients [8%] had hot flushes and five patients [1%] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group). Three (8%) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group. The most common late adverse events of grade 3 or worse were genitourinary events (29 [8%] in the radiotherapy alone group vs 26 [7%] in the radiotherapy plus goserelin group) and sexual disorders (20 [5%] vs 30 [8%]). No treatment-related deaths occurred. INTERPRETATION: Adding short-term androgen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable. Radiotherapy combined with short-term androgen suppression could be considered as a reasonable option in this population. FUNDING: French Ministry of Health, AstraZeneca, and La Ligue Contre le Cancer.

Concurrent and adjuvant docetaxel with three-dimensional conformal radiation therapy plus androgen deprivation for high-risk prostate cancer: preliminary results of a multicentre phase II trial.

BACKGROUND AND PURPOSE: We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas. METHODS: Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20mg/m(2)). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60mg/m(2)), every 3 weeks. Patients had to receive LHRH agonist during 3 years. RESULTS: The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3-4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced a grade 3 toxicity, and 15 patients experienced a grade 2 toxicity. With a median follow-up of 54 months, the 5-year clinical disease-free survival was 66.72% and the 5-year survival was 92.15%. CONCLUSIONS: 3D-CRT with androgen deprivation and concurrent weekly docetaxel, followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III randomized trial.

[Neoadjuvant hormonal treatment combined with external irradiation in the management of prostate cancer]. / L'association hormonothérapie néoadjuvante et irradiation externe dans les cancers de la prostate.

RTOG and EORTC trials have paved the way of the combination of radiation therapy and androgen suppression. Localized carcinoma with intermediate prognostic factors (cT2b, Gleason 7, or baseline PSA ranging between 10 and 20 ng/mL) may be submitted to a 4-month complete androgene blockade with 2 months before irradiation, unless to include patients in ongoing randomized trials. High risk cancers (cT2c, or Gleason > 7, or PSA > 20 ng/ml) should receive a 4-month or 6-month complete androgen blockade (RTOG trial 86-10), knowing that the results of EORTC trial 22961 are eagerly expected to tell us whether a 3- year androgen suppression is preferable. Very high risk prostate cancers, T3-4 N0 M0 or pelvic lymph node involvement (c or pN1) whatever the UICC T stage, need a long term androgen suppression of 3 years or more.

Boost radiotherapy in young women with ductal carcinoma in situ: a multicentre, retrospective study of the Rare Cancer Network.

BACKGROUND: Outcome data in young women with ductal carcinoma in situ (DCIS) are rare. The benefits of boost radiotherapy in this group are also unknown. We aimed to assess the effect of boost radiotherapy in young patients with DCIS. METHODS: We included 373 women from 18 institutions who met the following inclusion criteria: having tumour status Tis and nodal status (N)0, age 45 years or younger at diagnosis, and having had breast-conserving surgery. 57 (15%) patients had no radiotherapy after surgery, 166 (45%) had radiotherapy without boost (median dose 50 Gy [range 40-60]), and 150 (40%) had radiotherapy with boost (60 Gy [53-76]). The primary outcome was local relapse-free survival. FINDINGS: Median follow-up was 72 months (range 1-281). 55 (15%) patients had local relapse. Local relapse-free survival at 10 years was 46% (95% CI 24-67) for patients given no radiotherapy, 72% (61-83) for those given radiotherapy without boost, and 86% (78-93) for those given radiotherapy and boost (difference between all three groups, p<0.0001). Age, margin status, and radiotherapy dose were significant predictors of local relapse-free survival. Compared with patients who had no radiotherapy, those who had radiotherapy had a decreased risk of local relapse (without boost, hazard ratio 0.33 [95% CI 0.16-0.71], p=0.004; with boost, 0.15 [0.06-0.36], p<0.0001). INTERPRETATION: In the absence of randomised trials, boost radiotherapy should be considered in addition to surgery for breast-conserving treatment for DCIS.

[Indications of the association of radiotherapy and hormonal treatment in prostate cancer]. / Place de l'association de radiothérapie et d'hormonothérapie dans les cancers de la prostate.

RTOG and EORTC randomised phase III trials investigated combination of radiation therapy and hormonal treatment in locally advanced prostate cancer T2c-T4 N0-1 M0 (UICC 2002). Complete androgen blockade initiated 2 months prior to starting radiotherapy and stopped at the completion of radiotherapy vs radiation therapy alone, increased overall survival in patients with Gleason score 2-6. Adjuvant androgen suppression started at the end of the radiotherapy and continued indefinitely improved significantly overall survival of patients Gleason score 8 to 10. Complete androgen blockade in two months before and two months during radiation followed by 24 additional months of LHRH analogue alone improved overall survival of patients Gleason score 8-10 with respect to CAB alone. EORTC trial 22861 has shown that androgen suppression with LHRH analogue given during and for 3 years after external irradiation improved overall survival whatever the Gleason score. The role of hormonal treatment is currently assessed in localized prostate cancer (T1-2 N0) with poor prognostic factors: Gleason score 8-10, PSA>20 ng/ml.

MRI/TRUS data fusion for prostate brachytherapy. Preliminary results.

Prostate brachytherapy involves implanting radioactive seeds (I125 for instance) permanently in the gland for the treatment of localized prostate cancers, e.g., cT1c-T2a N0 M0 with good prognostic factors. Treatment planning and seed implanting are most often based on the intensive use of transrectal ultrasound (TRUS) imaging. This is not easy because prostate visualization is difficult in this imaging modality particularly as regards the apex of the gland and from an intra- and interobserver variability standpoint. Radioactive seeds are implanted inside open interventional MR machines in some centers. Since MRI was shown to be sensitive and specific for prostate imaging whilst open MR is prohibitive for most centers and makes surgical procedures very complex, this work suggests bringing the MR virtually in the operating room with MRI/TRUS data fusion. This involves providing the physician with bi-modality images (TRUS plus MRI) intended to improve treatment planning from the data registration stage. The paper describes the method developed and implemented in the PROCUR system. Results are reported for a phantom and first series of patients. Phantom experiments helped characterize the accuracy of the process. Patient experiments have shown that using MRI data linked with TRUS data improves TRUS image segmentation especially regarding the apex and base of the prostate. This may significantly modify prostate volume definition and have an impact on treatment planning.