Radiotherapy is the standard salvage treatment after radical prostatectomy. To date, the role of androgen deprivation therapy has not been formally shown. In this follow-up study, we aimed to update ...the results of the GETUG-AFU 16 trial, which assessed the efficacy of radiotherapy plus androgen suppression versus radiotherapy alone.
GETUG-AFU 16 was an open-label, multicentre, phase 3, randomised, controlled trial that enrolled men (aged ≥18 years) with Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed adenocarcinoma of the prostate (but no previous androgen suppression or pelvic radiotherapy), stage pT2, T3, or T4a (bladder neck involvement only) and pN0 or pNx according to the tumour, node, metastasis (TNM) staging system, whose prostate-specific antigen (PSA) concentration increased from 0·1 ng/mL to between 0·2 ng/mL and 2·0 ng/mL after radical prostatectomy, without evidence of clinical disease. Patients were assigned through central randomisation (1:1) to short-term androgen suppression (subcutaneous injection of 10·8 mg goserelin on the first day of irradiation and 3 months later) plus radiotherapy (3D conformal radiotherapy or intensity modulated radiotherapy of 66 Gy in 33 fractions, 5 days a week for 7 weeks) or radiotherapy alone. Randomisation was stratified using a permuted block method (block sizes of two and four) according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival in the intention-to-treat population. This post-hoc one-shot data collection done 4 years after last data cutoff included patients who were alive at the time of the primary analysis and updated long-term patient status by including dates for first local progression, metastatic disease diagnosis, or death (if any of these had occurred) or the date of the last tumour evaluation or last PSA measurement. Survival at 120 months was reported. Late serious adverse effects were assessed. This trial is registered on ClinicalTrials.gov, NCT00423475.
Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. At the time of data cutoff (March 12, 2019), the median follow-up was 112 months (IQR 102–123). The 120-month progression-free survival was 64% (95% CI 58–69) for patients treated with radiotherapy plus goserelin and 49% (43–54) for patients treated with radiotherapy alone (hazard ratio 0·54, 0·43–0·68; stratified log-rank test p<0·0001). Two cases of secondary cancer occurred since the primary analysis, but were not considered to be treatment related. No treatment-related deaths occurred.
The 120-month progression-free survival confirmed the results from the primary analysis. Salvage radiotherapy combined with short-term androgen suppression significantly reduced risk of biochemical or clinical progression and death compared with salvage radiotherapy alone. The results of the GETUG-AFU 16 trial confirm the efficacy of androgen suppression plus radiotherapy as salvage treatment in patients with increasing PSA concentration after radical prostatectomy for prostate cancer.
The French Health ministry, AstraZeneca, la Ligue Contre le Cancer, and La Ligue de Haute-Savoie.
To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer.
A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The ...primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules.
The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively (p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively (p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms (p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy (p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy (p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms.
High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity.
Summary 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.
Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate ...or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone.
This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis.
The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts.
ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study.
The purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC).
This retrospective ...study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models.
Median follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ΔTLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8-18, p = 0.002) and for patients with ΔTLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5-9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ΔSUVmax. Patients with MTV2> 23cc and ΔSUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1-15.4, p< 0.01).
Post-induction FDG PET might be an added value to assess the patients' prognosis in inoperable stage II/III NSCLC. TLG, ΔTLG as well as the association of MTV and ΔSUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.
Concomitant chemo-radiotherapy is the reference treatment for non-resectable locally-advanced Non-Small Cell Lung Cancer (NSCLC). Increasing radiotherapy total dose in the whole tumour volume has ...been shown to be deleterious. Functional imaging with positron emission tomography (PET/CT) offers the potential to identify smaller and biologically meaningful target volumes that could be irradiated with larger doses without compromising Organs At Risk (OAR) tolerance. This study investigated four scenarios, based on
FDG and
F-miso PET/CT, to delineate the target volumes and derive radiotherapy plans delivering up to 74Gy.
Twenty-one NSCLC patients, selected from a prospective phase II trial, had
FDG- and
F-miso PET/CT before the start of radiotherapy and
FDG PET/CT during the radiotherapy (42Gy). The plans were based planned on a standard plan delivering 66 Gy (plan 1) and on three different boost strategies to deliver 74Gy total dose in pre-treatment
FDG hotspot (70% of SUV
) (plan 2), pre-treatment
F-miso target (SUV
> 1.4) (plan 3) and per-treatment
FDG residual (40% of SUV
). (plan 4).
The mean target volumes were 4.8 cc (± 1.1) for
FDG hotspot, 38.9 cc (± 14.5) for
F-miso and 36.0 cc (± 10.1) for per-treatment
FDG. In standard plan (66 Gy), the mean dose covering 95% of the PTV (D95%) were 66.5 (± 0.33), 66.1 (± 0.32) and 66.1 (± 0.32) Gy for
FDG hotspot,
F-miso and per-treatment
FDG. In scenario 2, the mean D95% was 72.5 (± 0.25) Gy in
FDG hotspot versus 67.9 (± 0.49) and 67.9 Gy (± 0.52) in
F-miso and per-treatment
FDG, respectively. In scenario 3, the mean D95% was 72.2 (± 0.27) Gy to
F-miso versus 70.4 (± 0.74) and 69.5Gy (± 0.74) for
FDG hotspot and per-treatment
FDG, respectively. In scenario 4, the mean D95% was 73.1 (± 0.3) Gy to
FDG per-treatment versus 71.9 (± 0.61) and 69.8 (± 0.61) Gy for
FDG hotspot and
F-miso, respectively. The dose/volume constraints to OARs were matched in all scenarios.
Escalated doses can be selectively planned in NSCLC target volumes delineated on
FDG and
F-miso PET/CT functional images. The most relevant strategy should be investigated in clinical trials.
(RTEP5, NCT01576796 , registered 15 june 2012).
Characteristics of incisional hernia (IH) formation after live donor nephrectomy (LDN) are not well-defined. The goal of this study was to describe the incidence of IH within 3 years after LDN and ...identify risk factors contributing to their formation.
We performed a single-center, retrospective review of all LDN between February 2013 and October 2018. Patients with and without IH were compared based on donor and operative variables. Data were analyzed using chi-square tests with column proportions. Multivariable logistic regression with backward elimination was used to evaluate the likelihood of IH on the basis of potential risk factors.
Three hundred one individuals underwent live donor nephrectomy. Twenty-eight patients (9.3%) developed an IH, with a median time to development of 7 months (range: 2-24 months). Obesity (body mass index ≥30), periumbilical hand port, and vertical infraumbilical hand port were associated with increased risk of IH development on univariate analysis. On multivariate analysis, obesity and periumbilical hand port location were persistent risk factors for IH.
The incidence of IH after LDN is prevalent and associated with obesity and operative technique. Placing the hand port infraumbilical with a transverse fascial incision may reduce the risk of IH after LDN.
Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, ...including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection. Using automated delineation of the skeletal muscle, we have investigated the prognostic value of sarcopenia in locally advanced oesophageal cancer (LAOC) patients treated by curative-intent chemo-radiotherapy.
The clinical, nutritional, anthropometric, and functional-imaging (
FDG-PET/CT) data were collected in 97 patients treated between 2006 and 2012 in our institution. The skeletal muscle area was automatically delineated on cross-sectional CT images acquired at the 3rd. lumbar vertebra level and divided by the patient's squared height (SML3/h
) to obtain the Skeletal Muscle Index (SMI). The primary endpoint was overall survival probability.
Seventy-six deaths were reported. The median survival time was 27 95% Confidence Interval 23-40 months for the whole population. Univariate analyses (Cox Proportional Hazard Model) showed decreased survival probabilities in patients with reduced SMI, WHO > 0, Body Mass Index ≤21, and Nutritional Risk Index ≤97.5. Multivariate analyses showed that sarcopenia was the only significant prognostic factor (HR 2.32 1.24-4.34, p = 0.008). Using Receiver Operating Characteristics curves, the Area Under the Curve (AUC) was 0.73 in males (p = 0.0002, the optimal threshold being 51.5 cm
/m
. In women, the AUC was 0.65 (p = 0.19).
Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated exclusively by radiochemotherapy for a locally advanced oesophageal cancer. L3 CT images are easily gathered from
FDG-PET/CT acquisitions.
Stereotactic body radiotherapy (SBRT) is a treatment option for spine metastases. The International Spine Radiosurgery Consortium (ISRC) has published consensus guidelines for target delineation in ...spine SBRT. A new software called Elements™ Spine SRS by Brainlab
that includes the module Elements SmartBrush Spine (v3.0, Munich, Germany) has been developed specifically for SBRT treatment of spine metastases, and the latter provides the ability to perform semiautomatic clinical target volume (CTV) generation based on gross tumor volume (GTV) localization and guidelines. The aims of our study were to evaluate this software by studying differences in volumes between semiautomatic CTV contours compared to manual contouring performed by an expert radiation oncologist and to determine the dosimetric impact of these differences on treatment plans.
A total of 35 volumes ("Expert GTV" and "Expert CTV") from 30 patients were defined by a single expert. A semiautomatic definition of these 35 CTVs based on the location of "Expert GTV" and following ISRC guidelines was also performed in Elements SmartBrush Spine ("Brainlab CTV"). The spatial overlap between "Brainlab" and "Expert" CTVs was calculated using the Dice similarity coefficient (DSC). We considered a threshold of 0.80 or above to indicate that Elements SmartBrush Spine performed very well with adequate contours for clinical use. Two dosimetric treatment plans, each corresponding to a specific planning target volume (PTV; Expert PTV, Brainlab PTV), were created for 11 patients.
We showed that "Brainlab CTV" and "Expert CTV" mean volumes were 29.8 ± 16.1 and 28.7 ± 15.7 cm
, respectively (p = 0.23). We also showed that the mean DSC for semiautomatic contouring relative to expert manual contouring was 0.85 ± 0.08 and less than 0.80 in five cases. For metastases involving the vertebral body only (n = 13,37%), the mean DSC was 0.90 ± 0.03, and for ones involving other or several vertebral regions (n = 22.63%), the mean DSC was 0.81 ± 0.08 (p < 0.001). The comparison of dosimetric treatment plans was performed for equivalent PTV coverage. There were no differences between doses received by organs at risk (spinal cord and esophagus) for Expert and Brainlab PTVs, respectively.
The results showed that the semiautomatic method had quite good accuracy and can be used in clinical routine even for complex lesions.
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