Stereotactic body radiotherapy (SBRT) and elective nodal radiotherapy (ENRT) are being investigated as metastasis-directed treatments in oligorecurrent prostate cancer (PC); however, comparative data ...are still lacking.
To compare outcome and toxicity between both treatments. Primary endpoint was metastasis-free survival, adjusted for selected variables (aMFS).
This was a multi-institutional, retrospective analysis of 506 (SBRT: 309, ENRT: 197) patients with hormone-sensitive nodal oligorecurrent PC (five or fewer lymph nodes (LNs; N1/M1a), treated between 2004 and 2017. Median follow-up was 36 mo (interquartile range 23–56).
SBRT was defined as a minimum of 5 Gy per fraction to each lesion with a maximum of 10 fractions. ENRT was defined as a minimum dose of 45 Gy in up to 25 fractions to the elective nodes, with or without a simultaneous boost to the suspicious node(s). The choice of radiotherapy (RT) was at the discretion of the treating physician, with treatments being unbalanced over the centers.
In total, 506 patients from 15 different treatment centers were included. Primary treatment was radical prostatectomy, RT, or their combination. Nodal recurrences were detected by positron emission tomography/computer tomography (97%) or conventional imaging (3%). Descriptive statistics was used to summarize patient characteristics.
ENRT was associated with fewer nodal recurrences compared with SBRT (p < 0.001). In a multivariable analysis, patients with one LN at recurrence had longer aMFS after ENRT (hazard ratio: 0.50, 95% confidence interval 0.30–0.85, p = 0.009). Late toxicity was higher after ENRT compared with that after SBRT (16% vs. 5%, p < 0.01). Limitations include higher use of hormone therapy in the ENRT cohort and nonstandardized follow-up.
ENRT reduces the number of nodal recurrences as compared with SBRT, however at higher toxicity. Our findings hypothesize that ENRT should be preferred to SBRT in the treatment of nodal oligorecurrences. This hypothesis needs to be evaluated in a randomized trial.
This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal radiotherapy might be the preferred treatment.
In treating nodal oligorecurrent prostate cancer, elective nodal radiotherapy reduces nodal relapse compared with stereotactic body radiotherapy. However, elective nodal radiotherapy was associated with higher toxicity.
Abstract
Context
As patients are now living with prostate cancer for longer, the long-term impact of hormonal treatment on bone health is an increasingly debated subject.
Objective
To characterize ...the changes in bone mineral density (BMD) and bone turnover markers after degarelix administration in prostate cancer patients without bone metastases. To explore the predictive role of body composition on treatment induced bone loss.
Methods
BMD and body composition (lean body mass, fat body mass, and appendicular mass index ALMI) were assessed by dual X-ray absorptiometry on study entry and after 12 months of degarelix therapy. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline, and 6 and 12 months.
Results
Twenty-nine patients entered the study. Degarelix administration was associated with a significant decrease in BMD after 12 months (2.4% reduction from baseline at lumbar spine). Serum CTX and ALP increased significantly (median increase from baseline 99% and 19.3%, respectively). An inverse correlation was observed between ALMI and CTX, but not ALP, at both baseline (Pearson r = –0.62, P < .0001) and month 12 (Pearson r = –0.41, P = .032). Moreover, a significant inverse correlation between changes in ALMI and CTX at 12 months (Pearson r = –0.43, P = .019) and a direct relationship between changes of ALMI and ALP (Pearson r = 0.44, P = .016) during degarelix therapy were observed.
Conclusion
Degarelix administration is associated with a significant decrease in BMD and increase in bone turnover markers. ALMI is a promising predictor of bone loss in prostate cancer patients receiving androgen deprivation therapy, and ALMI changes during therapy are associated with bone turnover derangement favoring bone quality alterations.
Cetuximab and Radiation Therapy in Head and Neck Cancer Maddalo, Marta; Triggiani, Luca; Magrini, Prof, Stefano Maria ...
International journal of radiation oncology, biology, physics,
11/2019, Volume:
105, Issue:
3
Journal Article
The aim of this work was to investigate whether Caveolin-1 (Cav-1), a membrane scaffolding protein widely implicated in cancer, may play a role in radiation response in rhabdomyosarcoma (RMS), a ...pediatric soft tissue tumor. For this purpose, we employed human RD cells in which Cav-1 expression was stably increased via gene transfection. After radiation treatment, we observed that Cav-1 limited cell cycle arrest in the G2/M phase and enhanced resistance to cell senescence and apoptosis via reduction of p21Cip1/Waf1, p16INK4a and Caspase-3 cleavage. After radiotherapy, Cav-1-mediated cell radioresistance was characterized by low accumulation of H2AX foci, as confirmed by Comet assay, marked neutralization of reactive oxygen species (ROS) and enhanced DNA repair via activation of ATM, Ku70/80 complex and DNA-PK. We found that Cav-1-overexpressing RD cells, already under basal conditions, had higher glutathione (GSH) content and greater catalase expression, which conferred protection against acute treatment with hydrogen peroxide. Furthermore, pre-treatment of Cav-1-overexpressing cells with PP2 or LY294002 compounds restored the sensitivity to radiation treatment, indicating a role for Src-kinases and Akt pathways in Cav-1-mediated radioresistance. These findings were confirmed using radioresistant RD and RH30 lines generated by hypofractionated radiotherapy protocol, which showed marked increase of Cav-1, catalase and Akt, and sensitivity to PP2 and LY294002 treatment. In conclusion, these data suggest that concerted activity of Cav-1 and catalase, in cooperation with activation of Src-kinase and Akt pathways, may represent a network of vital mechanisms that allow irradiated RMS cells to evade cell death induced by oxidative stress and DNA damage.
•Cav-1 promoted RD cell survival after irradiation.•Cav-1 protected against cell senescence and apoptosis.•Cav-1 diminished oxidative stress and increased catalase expression.•Cav-1 enhanced DNA repair.•Src-kinase and Akt inhibition prevented radioresistance.
To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and ...costs.
In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage.
No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval CI 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores.
Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.
ARTO (ClinicalTrials.gov identifier: NCT03449719) is a multicenter, phase II randomized clinical trial testing the benefit of adding stereotactic body radiation therapy (SBRT) to abiraterone acetate ...and prednisone (AAP) in patients with oligometastatic castrate-resistant prostate cancer (CRPC).
All patients were affected by oligometastatic CRPC as defined as three or less nonvisceral metastatic lesions. Patients were randomly assigned 1:1 to receive either AAP alone (control arm) or AAP with concomitant SBRT to all the sites of disease (experimental arm). Primary end point was the rate of biochemical response (BR), defined as a prostate-specific antigen (PSA) decrease ≥50% from baseline measured at 6 months from treatment start. Complete BR (CBR), defined as PSA < 0.2 ng/mL at 6 months from treatment, and progression-free survival (PFS) were secondary end points.
One hundred and fifty-seven patients were enrolled between January 2019 and September 2022. BR was detected in 79.6% of patients (92%
68.3% in the experimental
control arm, respectively), with an odds ratio (OR) of 5.34 (95% CI, 2.05 to 13.88;
= .001) in favor of the experimental arm. CBR was detected in 38.8% of patients (56%
23.2% in the experimental
control arm, respectively), with an OR of 4.22 (95% CI, 2.12 to 8.38;
< .001). SBRT yielded a significant PFS improvement, with a hazard ratio for progression of 0.35 (95% CI, 0.21 to 0.57;
< .001) in the experimental versus control arm.
The trial reached its primary end point of biochemical control and PFS, suggesting a clinical advantage for SBRT in addition to first-line AAP treatment in patients with metastatic castration-resistant prostate cancer.
Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using ...different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by 18Ffluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio HR, 0.49 95% CI, 0.36-0.67; P < 0.0001), PFS2 (HR, 0.42 95% CI, 0.28-0.63; P < 0.0001), and overall survival (HR, 0.39 95% CI, 0.15-0.99; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent 68GaGa-PSMA-11 versus 18FF-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 95% CI, 0.26-1.00; P < 0.05; PFS2: HR, 0.24 95% CI, 0.09-0.60; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by 18Ffluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio HR, 0.49 95% CI, 0.36-0.67; P < 0.0001), PFS2 (HR, 0.42 95% CI, 0.28-0.63; P < 0.0001), and overall survival (HR, 0.39 95% CI, 0.15-0.99; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent 68GaGa-PSMA-11 versus 18FF-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 95% CI, 0.26-1.00; P < 0.05; PFS2: HR, 0.24 95% CI, 0.09-0.60; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.
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Background: ARTO (NCT03449719) is a multicentre, randomized phase II trial testing the benefit of concomitant stereotactic body radiation therapy (SBRT) and abiraterone acetate (AA)+ prednisone ...administration in oligometastatic Castrate Resistant Prostate Cancer (CRPC) patients. Results already showed significant benefit in terms of biochemical response and Progression Free Survival (PFS) in the experimental arm. To explore role of local treatment throughout the whole clinical history of these patients, here is reported a subgroup analysis focusing on impact of treatment (SBRT vs second line systemic therapy) after progression. Methods: Patients affected by oligometastatic CRPC (</= 3 non-visceral metastatic lesions) were enrolled in the trial and randomized 1:1 to receive either AA+ prednisone alone (control arm) or associated with concomitant SBRT on all sites of disease (treatment arm). PFS2 was defined as time between first progression event and second progression, death or last follow up. Cox regression analysis was performed to compare PFS2 in patients treated with SBRT on oligo-progressive metastatic sites vs patients undergoing second line systemic therapy (primarily taxane chemotherapy). Results: One hundred fifty-seven patients were enrolled in ARTO trial. At last follow up (August 2023), 77 patients progressed after abiraterone+ prednisone treatment (23 vs 54 in the experimental vs control arm, respectively). Of these, 14 received best supportive care and were excluded from the analysis, 23 underwent SBRT on oligo-progressive metastatic sites (17 and 6 originally randomized to the experimental vs control arm, respectively), 40 were treated with second line systemic treatment. A second progression event was detected in 14 patients. Median PFS 2 was 10 months (95% CI 10-17) and 10 months (95% CI 7-12) for patients undergoing SBRT vs second line treatment, respectively (HR 1.26, 95% CI 0.33-4.75, p 0.73). Conclusions: When oligoprogressive status is detected, SBRT may achieve similar benefit if compared to second line systemic treatment. These data, in the context of a randomized trial with positive results for primary endpoints, suggest that repeated SBRT may be a viable treatment option in selected patients. Clinical trial information: NCT03449719 .
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