20 research outputs found

    Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

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    <p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m<sup>2 </sup>weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m<sup>2 </sup>to 100 mg/m<sup>2</sup>. Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65‚Äď75 mg/m<sup>2 </sup>(induction phase) followed by 75‚Äď85 mg/m<sup>2 </sup>(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

    Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

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    <p>Abstract</p> <p>Background</p> <p>To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.</p> <p>Methods</p> <p>Four Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre.</p> <p>Results</p> <p>Clinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ‚ȧ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ‚ȧ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients.</p> <p>Conclusions</p> <p>In clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.</p

    Adult Granulosa Cell Tumor in Pregnancy: A New Case and a Review of the Literature

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    Granulosa cell tumors are rare ovarian tumors that can arise during pregnancy. We present a new case of recurrent adult granulosa cell tumor (AGCT) in pregnancy and a systematic review of the literature. The new case described is a 41-year-old woman G5P1122 with a prior history of AGCT that was referred to our center at 29 weeks because of a symptomatic abdominal mass, compatible with a possible recurrence of AGCT. At 36 + 3 weeks, she underwent a cesarean delivery for preterm labor and a total hysterectomy with a radical surgical staging. A healthy female infant was delivered. The patient received a platinum-based chemotherapy, with a 26-month follow-up negative for recurrence. Analyzing our case with the four identified by the literature review, three were recurrent and two were primary AGCT. Only one required surgery for AGCT at 15 weeks, while another underwent chemotherapy in pregnancy. In the other three cases, surgery for AGCT was done at the time of cesarean delivery. There were three cases of preterm delivery. All five pregnancies resulted in the birth of live babies with weight adequate for gestational age. In conclusion, AGCT diagnosed in pregnancy is rare, reported in only five cases. All gave birth to live babies in the third trimester, and maternal outcome at up to 18 months showed no recurrence

    Preoperative endogenous testosterone density predicts disease progression from localized impalpable prostate cancer presenting with PSA levels elevated up to 10 ng/mL

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    To investigate endogenous testosterone density (ETD) predicting disease progression from clinically localized impalpable prostate cancer (PCa) presenting with prostate-specific antigen (PSA) levels elevated up to 10&nbsp;ng/mL and treated with radical prostatectomy

    Clinical implications of endogenous testosterone density on prostate cancer progression in patients with very favorable low and intermediate risk treated with radical prostatectomy

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    : We tested the association between endogenous testosterone density (ETD; the ratio between endogenous testosterone [ET] and prostate volume) and prostate cancer (PCa) aggressiveness in very favorable low- and intermediate-risk PCa patients who underwent radical prostatectomy (RP). Only patients with prostate-specific antigen (PSA) within 10 ng ml-1, clinical stage T1c, and International Society of Urological Pathology (ISUP) grade group 1 or 2 were included. Preoperative ET levels up to 350 ng dl-1 were classified as abnormal. Tumor quantitation density factors were evaluated as the ratio between percentage of biopsy-positive cores and prostate volume (biopsy-positive cores density, BPCD) and the ratio between percentage of cancer invasion at final pathology and prostate weight (tumor load density, TLD). Disease upgrading was coded as ISUP grade group &gt;2, and progression as recurrence (biochemical and/or local and/or distant). Risk associations were evaluated by multivariable Cox and logistic regression models. Of 320 patients, 151 (47.2%) had intermediate-risk PCa. ET (median: 402.3 ng dl-1) resulted abnormal in 111 (34.7%) cases (median ETD: 9.8 ng dl-1 ml-1). Upgrading and progression occurred in 109 (34.1%) and 32 (10.6%) cases, respectively. Progression was predicted by ISUP grade group 2 (hazard ratio [HR]: 2.290; P = 0.029) and upgrading (HR: 3.098; P = 0.003), which was associated with ISUP grade group 2 (odds ratio [OR]: 1.785; P = 0.017) and TLD above the median (OR: 2.261; P = 0.001). After adjustment for PSA density and body mass index (BMI), ETD above the median was positively associated with BPCD (OR: 3.404; P &lt; 0.001) and TLD (OR: 5.238; P &lt; 0.001). Notably, subjects with abnormal ET were more likely to have higher BPCD (OR: 5.566; P = 0.002), as well as TLD (OR: 14.998; P = 0.016). Independently by routinely evaluated factors, as ETD increased, BPCD and TLD increased, but increments were higher for abnormal ET levels. In very favorable cohorts, ETD may further stratify the risk of aggressive PCa

    Preoperative endogenous total testosterone predicts prostate cancer progression: results in 580 consecutive patients treated with robot assisted radical prostatectomy for clinically localized disease

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    Purpose: To test the role of endogenous total testosterone (ETT) as a predictor of prostate cancer (PCa) progression in patients treated with robot assisted radical prostatectomy for clinically localized disease. Methods: Between November 2014 and December 2019, 580 consecutive patients were evaluated. Preoperative ETT levels were classified as‚ÄȂȧ‚ÄČ350&nbsp;ng/dL vs.‚ÄČ&gt;‚ÄČ350&nbsp;ng/dL. The associations between ETT levels and the risk of PCa progression, defined as any event of biochemical recurrence and/or local recurrence and/or distant metastases, or other clinical and pathological factors were evaluated by regression analyses. Results: Preoperative ETT levels resulted‚ÄȂȧ‚ÄČ350&nbsp;ng/dL in 173 (29.8%) patients. Disease progression occurred in 101 (17.1%) cases. Progressing patients were more likely to present with PSA levels‚ÄČ&gt;‚ÄČ10&nbsp;ng/mL, as well as with unfavorable tumor grade (ISUP 4-5) and stage (pT3b) at final pathology, but less likely to have ETT levels‚ÄȂȧ‚ÄČ350&nbsp;ng/mL. On clinical multivariable Cox regression models, ETT‚ÄȂȧ‚ÄČ350&nbsp;ng/mL exhibited a statistically significant protective effect on tumor progression (hazard ratio: 0.57, p‚ÄČ=‚ÄČ0.013). Subjects presenting with ETT levels‚ÄȂȧ‚ÄČ350&nbsp;ng/mL were less likely to harbor ISUP 4-5 tumor grade either at biopsy (odds ratio [OR]: 0.46, p‚ÄČ=‚ÄČ0.028) or final pathology (OR: 0.45, p‚ÄČ=‚ÄČ0.032). Conclusions: At PCa diagnosis, ETT, which associates with ISUP tumor grade, is an independent predictor of disease progression. Accordingly, as ETT decreases to levels‚ÄȂȧ‚ÄČ350&nbsp;ng/dL, the risk of unfavorable tumor grade decreases, and a more favorable prognosis is expected. Preoperative ETT levels may allow further patient stratification along prognostic risk groups

    Normal preoperative endogenous testosterone levels predict prostate cancer progression in elderly patients after radical prostatectomy

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    Background: The impact of senior age on prostate cancer (PCa) oncological outcomes following radical prostatectomy (RP) is controversial, and further clinical factors could help stratifying risk categories in these patients. Objective: We tested the association between endogenous testosterone (ET) and risk of PCa progression in elderly patients treated with RP. Design: Data from PCa patients treated with RP at a single tertiary referral center, between November 2014 and December 2019 with available follow-up, were retrospectively evaluated. Methods: Preoperative ET (classified as normal if &gt;350‚ÄČng/dl) was measured for each patient. Patients were divided according to a cut-off age of 70‚ÄČyears. Unfavorable pathology consisted of International Society of Urologic Pathology (ISUP) grade group &gt;2, seminal vesicle, and pelvic lymph node invasion. Cox regression models tested the association between clinical/pathological tumor features and risk of PCa progression in each age subgroup. Results: Of 651 included patients, 190 (29.2%) were elderly. Abnormal ET levels were detected in 195 (30.0%) cases. Compared with their younger counterparts, elderly patients were more likely to have pathological ISUP grade group &gt;2 (49.0% versus 63.2%). Disease progression occurred in 108 (16.6%) cases with no statistically significant difference between age subgroups. Among the elderly, clinically progressing patients were more likely to have normal ET levels (77.4% versus 67.9%) and unfavorable tumor grades (90.3% versus 57.9%) than patients who did not progress. In multivariable Cox regression models, normal ET [hazard ratio (HR)‚ÄČ=‚ÄČ3.29; 95% confidence interval (CI)‚ÄČ=‚ÄČ1.27-8.55; p‚ÄČ=‚ÄČ0.014] and pathological ISUP grade group &gt;2 (HR‚ÄČ=‚ÄČ5.62; 95% CI‚ÄČ=‚ÄČ1.60-19.79; p‚ÄČ=‚ÄČ0.007) were independent predictors of PCa progression. On clinical multivariable models, elderly patients were more likely to progress for normal ET levels (HR‚ÄČ=‚ÄČ3.42; 95% CI‚ÄČ=‚ÄČ1.34-8.70; p‚ÄČ=‚ÄČ0.010), independently by belonging to high-risk category. Elderly patients with normal ET progressed more rapidly than those with abnormal ET. Conclusion: In elderly patients, normal preoperative ET independently predicted PCa progression. Elderly patients with normal ET progressed more rapidly than controls, suggesting that longer exposure time to high-grade tumors could adversely impact sequential cancer mutations, where normal ET is not anymore protective on disease progression

    Advanced age portends poorer prognosis after radical prostatectomy: a single center experience

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    Introduction and objective Although advanced age doesn't seem to impair oncological outcomes after robot-assisted radical prostatectomy (RARP), elderly patients have increased rates of prostate cancer (PCa) related deaths due to a higher incidence of high-risk disease. The potential unfavorable impact of advanced age on oncological outcomes following RARP remains an unsettled issue. We aimed to evaluate the oncological outcome of PCa patients &gt; 69 years old in a single tertiary center. Materials and methods 1143 patients with clinically localized PCa underwent RARP from January 2013 to October 2020. Analysis was performed on 901 patients with available follow-up. Patients &gt;= 70 years old were considered elderly. Unfavorable pathology included ISUP grade group &gt; 2, seminal vesicle, and pelvic lymph node invasion. Disease progression was defined as biochemical and/or local recurrence and/or distant metastases. Results 243 cases (27%) were classified as elderly patients (median age 72 years). Median (IQR) follow-up was 40.4 (38.7-42.2) months. Disease progression occurred in 159 cases (17.6%). Elderly patients were more likely to belong to EAU high-risk class, have unfavorable pathology, and experience disease progression after surgery (HR = 5.300; 95% CI 1.844-15.237; p = 0.002) compared to the younger patients. Conclusions Elderly patients eligible for RARP are more likely to belong to the EAU high-risk category and to have unfavorable pathology that are independent predictors of disease progression. Advanced age adversely impacts on oncological outcomes when evaluated inside these unfavorable categories. Accordingly, elderly patients belonging to the EAU high-risk should be counseled about the increased risk of disease progression after surgery
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