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1.
Int J Cancer ; 146(6): 1643-1651, 2020 03 15.
Article in English | MEDLINE | ID: mdl-31318983

ABSTRACT

The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real-life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty-four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Bevacizumab/therapeutic use , Carcinoma, Renal Cell/mortality , Everolimus/therapeutic use , Female , France/epidemiology , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Molecular Targeted Therapy/adverse effects , Molecular Targeted Therapy/methods , Patient Selection , Prognosis , Prospective Studies , Risk Factors , Survival Analysis , Time Factors
2.
PLoS One ; 14(1): e0210514, 2019.
Article in English | MEDLINE | ID: mdl-30682036

ABSTRACT

OBJECTIVES: No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the dose to the involved seminal vesicles (ISV) while respecting the dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer. MATERIALS AND METHODS: This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data. RESULTS: A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed doses (Gy) to the prostate and to the ISV were 77 (70-80) and 76 (46-80), respectively. The dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The dose to the pelvic lymph node and the age were predictive of late digestive toxicity. CONCLUSION: IMRT for T3b prostate cancer allows delivery of a curative dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.


Subject(s)
Androgen Antagonists/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Aged, 80 and over , Androgen Antagonists/adverse effects , Chemoradiotherapy , Digestive System Diseases/chemically induced , Digestive System Diseases/diagnosis , Humans , Lymph Nodes/drug effects , Lymph Nodes/radiation effects , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prostate/diagnostic imaging , Prostate/drug effects , Prostate/radiation effects , Radiation Injuries/diagnosis , Radiation Injuries/etiology , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Seminal Vesicles/diagnostic imaging , Seminal Vesicles/drug effects , Seminal Vesicles/radiation effects
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