Search

Introduction: Radiotherapy can diminish quality of life (QoL) for prostate cancer patients. Our objective was to evaluate the effect of radiotherapy on QoL in men aged 75 years or older treated with radiotherapy for a localized prostate cancer, and to identify predictors of reduced QoL., Patients and Methods: We prospectively administered a battery of geriatric (MNA, GDS, Get up and Go Test, CIRS-G, ADL, IADL, MMSE), toxicity (IPSS; IIEF 5), and QoL (QLQ C30) screening tests in 100 elderly patients before and two months after prostate cancer radiotherapy (NCT 02876237). Patients ≥ 75 years undergoing radiotherapy with a curative intent for localized prostate cancer with or without androgen deprivation therapy (ADL) were eligible for study inclusion. Correlations between patient-assessed QoL and tumor characteristics, radiotherapy treatment or CGA parameters were sought using the Fisher or the Mann and Whitney tests. Changes in QoL parameters over time were analyzed using the Wilcoxon signed-rank test., Results: At study entry, scores for IADL impairments were present in 51%, reduced autonomy in activities of daily living in 16%, cognitive impairment found in 20%, depression-related symptoms in 31%, and 66% of patients had significant co-morbidities. Eight percent were judged to be at risk of fall and 2% were found to be undernourished. Severely impaired (IPSS ≥ 20) urinary function was observed in 11.2% and 13.5% of patients before and two months after completion of radiotherapy respectively. Significantly decreased QoL (> 20 points) at two months after treatment was found in 13% of patients and a moderate but clinically relevant reduction (10 to 20 points) in 17% of patients. No tumor characteristic, treatment, or oncogeriatric parameter was predictive of reduced QoL following prostate cancer radiotherapy., Conclusion: Despite sometimes markedly diminished oncogeriatric parameters, prostate cancer radiotherapy was generally well tolerated in these elderly patients. We found no predictive factor to determine which patients would experience impaired quality of life following radiotherapy.

Abstract: Five‐year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of a national series of adult patients with RMS in a large study. The study population consisted of two different cohorts: a retrospective cohort (157 adult patients treated in 13 reference centers between 05/1981 and 02/2010) and the prospective cohort (292 patients with RMS diagnosed and treated between 01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive analysis of patients’ characteristics and prognostic factors was conducted on both series which were compared. In the retrospective series, histological subtypes were embryonal (E‐RMS) for 21% of patients, alveolar (A‐RMS) for 35% of patients, and “adult‐type” P‐RMS (pleomorphic, spindle cell RMS, not otherwise specified) (P) for 44% patients. This distribution significantly differed in the prospective cohort: A‐RMS: 18%; E‐RMS: 17%; and P‐RMS 65%. With a median follow‐up of 8.5 years, 5‐year OS for localized RMS and advanced RMS (with nodes and/or metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33, and 16 months for E‐RMS, A‐RMS, and P‐RMS, respectively, in the retrospective cohort. The median OS was less than 40 months for the prospective nationwide cohort for the entire population. In a multivariate analysis of the retrospective study, independent prognostic factors for OS were A‐RMS, R0 resection, and adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric chemotherapy (CT) regimen are independent prognostic factors. Adult patients with RMS have a poorer overall survival than pediatric patients, and survival varies considerably across histological subtypes. [ABSTRACT FROM AUTHOR]

Background: Metastatic prostate cancer remains a common cause of death in Europe, and improvements in management of the disease are urgently needed. The advent of positron-emission tomography (PET) imaging enhanced with fluorocholine has led to the identification of a new sub-group of metastatic prostate cancer patients: those with so-called oligometastatic disease. Presenting with a low burden of metastatic disease (≤5 lesions), this new sub-group lies between true metastatic prostate cancer patients for whom androgen- deprivation therapy (ADT) is the mainstay of treatment, and patients with a rising PSA, but no visible lesion on conventional imaging, in whom intermittent ADT has been shown to be no less effective than continuous ADT. One might conclude that intermittent ADT would also be the standard of care for oligometastatic prostate cancer patients, but radical strategies such as extensive lymphadenectomy or high-dose radiotherapy have been suggested as another means to delay the need for ADT, and increase its effectiveness once initiated. This study will explore the role of salvage pelvic image-guided intensity-modulated radiation therapy (IMRT) combined with ADT administered for 6 months in pelvic oligometastatic patients in prolonging the failure-free interval between two consecutive ADT courses, or even to cure selected patients with limited metastatic burden.Methods/design: We plan to assess the two year outcome in oligometastatic prostate cancer patients (1-5 pelvic oligometastases) treated concomitantly with high-dose IMRT (54 Gy, 30 fractions to the pelvis and 66 Gy, 30 fractions to the lymph nodes) and ADT for six months.Discussion: This multicenter prospective phase II study will yield new data regarding the safety and efficacy of high-dose radiotherapy combined with ADT and will provide a basis for a larger phase III study to examine the role of radiotherapy in this population currently treated only with hormone therapy.Trial Registration: NCT02274779 , date of registration: 23/10/14. [ABSTRACT FROM AUTHOR]

Purpose: PET is a powerful tool for assessing targeted therapy. Since F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Methods: Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Results: Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT ( P = 0.011) and SUV ( P = 0.038) calculated before pRAIT and impact on DT ( P = 0.034), RECIST ( P = 0.009), PET ( P = 0.009), and combined response ( P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis. Conclusion: F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment. [ABSTRACT FROM AUTHOR]

Background: Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment. Methods: This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/2/day), LV (75 mg/ day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate. Results: Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days). Conclusion: Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events. [ABSTRACT FROM AUTHOR]

Abstract. This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of [sup 89]Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed. [ABSTRACT FROM AUTHOR]

Curative radiotherapy for prostate cancer is common in the elderly. However, concerns about potential toxicity have inhibited access to radiotherapy for this population, for whom preserving quality of life (QoL) is crucial. The primary endpoint was to identify predictors of impaired QoL in men aged 75 years or older treated with curative intent radiotherapy with or without androgen deprivation therapy (ADT) for localized prostate cancer. We prospectively performed comprehensive geriatric assessment (CGA) and administered QoL questionnaires to 208 elderly (>75 years) patients prior to, plus two and six months after, radiotherapy (NCT 02876237). The median age of the patients was 77 years (range 75–89). At the start of the study, comorbidities were highlighted in 65% of patients: 23% were depressed, 23% had cognitive impairment, and 16% had reduced independence. At six months, 9% of patients had a consistently decreased QoL (>20 points), and a further 16% had a more moderate reduction (10 to 20 points) in QoL. None of the parameters studied (tumor characteristic, treatment, or oncogeriatric parameters) were predictive of a reduced QoL following radiotherapy. Though co-existing geriatric impairment was common, QoL was maintained for 75% of patients six months after radiotherapy. CGA was poorly predictive of tolerance of prostatic radiotherapy. Geriatric assessments dedicated to quality of life following radiotherapy need to be developed. [ABSTRACT FROM AUTHOR]

Abstract Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using 18F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk prostate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiotherapy induces early prostate tumor reoxygenation. [ABSTRACT FROM AUTHOR]

Purpose: To determine prospectively intermediate-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). Patients and Methods: Fifty-five patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy). Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 6, and 18 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30(+3) and QLQ-PR25. Results: Median age was 73 years (range, 54–80 years). Risk categories were 18% low risk, 60% intermediate risk, and 22% high risk; 45% of patients received hormonal therapy (median duration, 6 months). The incidence of urinary and bowel toxicity immediately after IMRT was, respectively, 38% and 13% (Grade 2) and 2% and none (Grade 3); at 18 months it was 15% and 11% (Grade 2) and none (Grade 3). Significant worsening of QoL was reported at 2 months with regard to fatigue (+11.31, p = 1.10−7), urinary symptoms (+9.07, p = 3.10−11), dyspnea (+7.27, p = 0.008), and emotional (−7.02, p = 0.002), social (−6.36, p = 0.003), cognitive (−4.85, p = 0.004), and physical (−3.39, p = 0.007) functioning. Only fatigue (+5.86, p = 0.003) and urinary symptoms (+5.86, p = 0.0004) had not improved by 6 months. By 18 months all QoL scores except those for dyspnea (+8.02, p = 0.01) and treatment-related symptoms (+4.24, p = 0.01) had returned to baseline. These adverse effects were exacerbated by hormonal therapy. Conclusion: High-dose IMRT with accurate positioning induces only a temporary worsening of QoL. [Copyright &y& Elsevier]