Acquired resistance occurs in metastatic hormone receptor–positive breast cancer patients. The addition of interferon beta/interleukin-2 immunotherapy to first-line salvage hormone therapy (HT) ...prolonged progression-free (PFS) and overall survivals (OS) in 26 patients, as compared with 30 historical controls and literature data. This was a 2 : 1 ratio case–control retrospective observational study. The cases were from an open pilot study, started in 1992, and controls were recruited in 2006. The planned mean follow-up time was the time at which more than 80% of controls progressed. The median PFS was significantly longer in the cases than that in controls, 33.1 (95% CI 24.5–41.8) vs 18 (95% CI 12.1–23.8) months (
p
< 0.0001). Also, median OS was significantly longer in the cases, 81 vs 62 (95% CI 48.1–75.9) months (
p
< 0.0029). When analysis of the 2 groups was adjusted for the disease-free interval (DFI), hormone receptor status, HER2, site of metastases and molecular-targeted therapies, the hazard ratio for PFS and for OS in the cases increased from 2.347 to 3.090 and from 1.874 to 2.147, respectively. This occurred in spite of the higher proportion of controls (82% vs 7.1%) treated with aromatase inhibitors (AIs), while selective oestrogen receptor modulators (SERMs) were given to 92.9% of the cases and to 18% of the control group (
p
< 0.0001). Immunotherapy significantly prolonged PFS and OS during conventional first-line HT. A multi-centre randomised clinical trial is advised to enter this immunotherapy into clinical practice.
Key messages
• Acquired resistance occurs in metastatic endocrine-dependent breast cancer patients.
• Interferon beta-interleukin-2 immunotherapy added to first-line salvage hormone therapy prolonged progression-free (PFS) and overall (OS) survivals in 26 patients of a pilot study as compared with 30 historical controls.
• In this 2:1 ratio case–control prospective observational study, the PFS median time was significantly longer in the study group than that in controls, 33.1 (95% CI 24.5–41.8) vs 18 (95% CI 12.1–23.8) months (
p
< 0.0001).
• Also, the OS median time was significantly longer in the study group, 81 vs 62 (95% CI 48.1–75.9) months (
p
< 0.0029).
Background
If Parkinson’s Disease (PD) may represent a risk factor for Coronavirus disease 2019 (COVID-19) is debated and there are few data on the direct and indirect effects of this pandemic in PD ...patients.
Objective
In the current study we evaluated the prevalence, mortality and case-fatality of COVID-19 in a PD cohort, also exploring possible risk factors. We also aimed to investigate the effect of lockdown on motor/non-motor symptoms in PD patients as well as their acceptability/accessibility to telemedicine.
Method
A case-controlled survey about COVID-19 and other clinical features in PD patients living in Tuscany was conducted. In non-COVID-19 PD patients motor/non-motor symptoms subjective worsening during the lockdown as well as feasibility of telemedicine were explored.
Results
Out of 740 PD patients interviewed, 7 (0.9%) were affected by COVID-19, with 0.13% mortality and 14% case-fatality. COVID-19 PD patients presented a higher presence of hypertension (
p
< 0.001) and diabetes (
p
= 0.049) compared to non-COVID-19. In non-COVID-19 PD population (
n
= 733) about 70% did not experience a subjective worsening of motor symptoms or mood, anxiety or insomnia. In our population 75.2% of patients was favorable to use technology to perform scheduled visits, however facilities for telemedicine were available only for 51.2% of cases.
Conclusion
A higher prevalence of COVID-19 respect to prevalence in Tuscany and Italy was found in the PD population. Hypertension and diabetes, as for general population, were identified as risk factors for COVID-19 in PD. PD patients did not experience a subjective worsening of symptoms during lockdown period and they were also favorable to telemedicine, albeit we reported a reduced availability to perform it.
Background
The purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric non-medullary ...thyroid carcinoma, in order to tailor the therapeutic strategy to be adopted for patients with family history.
Methods
We analyzed the records of 76 pediatric patients that underwent surgery for differentiated thyroid cancer from 2014 to 2019 at the Surgical Pathology Department of the University of Pisa, Italy. Among these, 20 (26,3%) had positive family history (familial non-medullary thyroid carcinoma—FNMTC group) while 56 (73.7%) were affected by sporadic forms (sporadic non-medullary thyroid carcinoma—SNMTC group).
Results
In our study, the correlation between the FNMTC and the SNMTC group showed no difference in terms of tumor features like multifocality, bilaterality, capsular/extracapsular invasion and the presence of vascular emboli. A statistical significance, on the other hand, was revealed by observation of clinical outcomes, such as distant metastasis (
p
= 0,022), persistence of disease (
p
= 0,054) and necessity of radioiodine sessions (
p
= 0,005).
Conclusions
These findings suggest that family history may have an independent role on the outcome, expressing its action through an intrinsic more aggressive biological behavior. Therefore, familial non-medullary thyroid carcinoma in children represents a nosological entity that requires an accurate pre-operative evaluation, an adequate surgical strategy and a careful follow up.
Modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine + nab-paclitaxel (GemNab) regimens represent a standard treatment in advanced pancreatic cancer (aPC). DPYD and UGT1A1 variants are relevant ...predictors of fluoropyrimidine and irinotecan-associated adverse events (AEs). Furthermore, data about the associations between polymorphisms in ABCB and CDA genes and GemNab-related toxicities are still controversial. The present study analyzes the association between DPYD, UGT, ABCB1, CDA variants, and AEs in aPC patients (pts) treated with mFOLFIRINOX or GemNab. Blood samples collected from 104 aPC pts treated with mFOLFIRINOX and 63 with GemNab were tested for DPYD c.1679T>G, IVS14+1G>A, c.2194G>A, c.2846A>T, UGT1A1*28, CDA c.79A>C, and ABCB1 c.1236C>T, c.2677G>T/A, c.3435C>T by real-time PCR and automatic sequencing. In mFOLFIRINOX cohort, DPYD IVS14+1GA genotype was associated with G4 hematological AEs, while the UGT1A1*28 significantly correlated with the risk of thrombocytopenia (p = 0.006). In the GemNab cohort, a significant association between CDA c.79CC and high-grade nausea was observed (p = 0.002). Moreover, the presence of at least a mutant allele in ABCB1 increased the risk of overall hematological AEs (p = 0.01), both further strengthened by the presence of CDA c.79CC (p = 0.0002). DPYD IVS14+1A allele is confirmed to be associated with fluoropyrimidine life-threatening toxicities, and UGT1A1*28 is related with a higher risk of hematologic AEs following irinotecan treatment. CDA c.79C and ABCB1 c.1236T, c.2677T/A, and c.3435T mutant alleles are predictive biomarkers of GemNab-related AEs. All these variants should be considered in aPC pts candidate to mFOLFIRINOX or GemNab treatments.
Background
Our purpose was to assess the performance of ESR iGuide for assisting the selection of the most appropriate imaging tests based on clinical signs and symptoms in patients with ...hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC).
Methods
We retrospectively reviewed the medical records of 113 patients with a final diagnosis of HCC or CC. Data from a cohort of 40 patients with a reported clinical history suggestive for either disease, who had undergone at least their first imaging test related to their condition at the same Institution, were entered into ESR iGuide. The appropriateness level of the diagnostic tests suggested by ESR iGuide was compared with that of the tests actually performed.
Results
All patients underwent several imaging examinations, ranging from a minimum of 1 to a maximum of 4, for a total of 98 diagnostic procedures. Of these, 79.6% (78/98) were considered “
usually appropriate
” by ESR iGuide, 11.2% (11/98) were designated as “
may be appropriate
”, and 9.2% (9/98) were not even suggested. Given a total estimated cost of €14,016 for the 98 examinations performed within the regional (BLINDED) healthcare system, the usage of ESR iGuide would have allowed saving €3033 (21.6%) due to inappropriate testing.
Conclusions
In patients with HCC or CC, ESR iGuide can be effective in guiding the selection of the appropriate imaging examinations and cutting costs due to inappropriate testing.
Background
Retroperitoneal fibrosis (RF) is a rare disease of unclear etiology characterized by the presence of fibroinflammatory tissue in the retroperitoneal space, which can entrap and obstruct ...retroperitoneal structures, notably the ureters. The disease responds well to steroid therapy, but tends to recur even after years. The aim of our study was to evaluate the long-term renal outcome of patients affected by idiopathic retroperitoneal fibrosis looking for predictive risk factors for recurrence of the disease and progression to end-stage renal disease.
Methods
Retrospective observational study of patients with idiopathic RF diagnosed from 2004 to 2017 and follow-up of at least 1 year after the end of first course therapy with steroid, with or without tamoxifen (TMX) and with urological procedures when applicable.
Results
Forty-three patients were included in the study. The follow-up was 93 ± 52 months. All the patients obtained remission after therapy that was maintained until the last observation in 26 of them. In 17 patients, there was at least one recurrence. Risk factors associated with relapse were identified and resulted in smoking habit, onset with acute kidney injury (AKI), low back pain and antinuclear antibodies (ANA) positivity. Renal function remained fairly stable during the long-term follow-up. The renal end-point (doubling of serum creatinine or ESRD) occurred in 8% of the patients; however, eGFR in patients with relapse was similar to that of non-recurrent at the diagnoses, but it decreased over time more in the relapsing than in non-relapsing patients (
p
group = 0.20;
p
time = 0.001;
p
time × group interactions = 0.04). Based on these 4 predictor conditions, patients were divided into “low risk” (with 0–1 risk factor), and “high risk” (3–4 risk factors). The renal end-point occurred in 40% of high-risk patients, while none of the low-risk patients reached it (
p
= 0.02).
Conclusions
Smoking habit, AKI at diagnosis, ANA positivity and lumbar pain were associated with relapse of RF after initial remission due to steroid and/or TMX therapy; the combination of these conditions was also predictive of worse renal function outcome. Identification of risk factors for relapse can be useful not only to modulate the choice, the dosage of first-line treatment and the duration of maintenance therapy but also for preventing a progressive loss of kidney function, as well.
Circulating cell-free DNA (cfDNA) may help understand the molecular response to pharmacologic treatment and provide information on dynamics of clonal heterogeneity. Therefore, this study evaluated ...the correlation between treatment outcome and activating EGFR mutations (act-EGFR) and T790M in cfDNA in patients with advanced NSCLC given osimertinib.
Thirty-four NSCLC patients resistant to first/second-generation EGFR-TKIs, positive for both act-EGFR and T790M in cfDNA at the time of progression were enrolled in this study. Plasma samples were obtained at osimertinib baseline and after 3 months of therapy; cfDNA was analyzed by droplet digital PCR and results were expressed as mutant allele frequency (MAF).
At baseline, act-EGFR MAF was significantly higher than T790M (p < 0.0001). act-EGFR MAF and T790M/act-EGFR MAF ratio were significantly correlated with disease response (p = 0.02). Cut-off values of act-EGFR MAF and T790M/act-EGFR ratio of 2.6% and 0.22 were found, respectively. The PFS of patients with act-EGFR MAF of > 2.6% and < 2.6%, were 10 months vs. not reached, respectively (p = 0.03), whereas patients with T790M/act-EGFR ≤ 0.22 had poorer PFS than patients with a value of > 0.22 (6 months vs. not reached, respectively, p = 0.01).
act-EGFR MAF and T790M/act-EGFR MAF ratio are potential markers of outcome in patients treated with osimertinib.
To compare the efficacy of intraoperative localized and 360° laser retinopexy in cases of rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy and air tamponade.
In this ...interventional, prospective, randomized, comparative study, 93 consecutive cases of RRD were enroled. After randomization 48 eyes received circumferential, while 45 underwent localized intraoperative laser retinopexy. Number and position of the retinal breaks, presence of proliferative vitreoretinopathy and/or lattice degeneration were recorded. Anatomical and visual outcome of the two groups were compared at 6 months postoperatively.
Baseline characteristics did not significantly differ between groups. The single-operation reattachment rate was 86.66% in localized group and 89.58% in 360° group. The difference was not significant. (P = 0.46, χ
test). At 6 months postoperatively, visual acuity (logMAR) was 0.06 ± 0.05 in localized group and 0.05 ± 0.03 in 360° group. The difference was not statistically significant (P = 0.673, t-test).
Localized laser resulted to be as effective as 360° laser application; this may lead some advantages in term of lower invasiveness, reduction risk of complications and time saving.
Objective
Markers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure ...recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features.
Methods
We compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year (“cases”) after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG (“controls”). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the “cases”, or 1‐year seizure freedom for “controls”). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact‐free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods.
Results
Both the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut‐off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity.
Significance
The occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.
Placement of flow-diverters across the ostia of major ICA branches carries a risk of arterial occlusion. We determined the rate of occlusion of the supraclinoid ICA branches and the related symptoms, ...following coverage with flow-diverters.
A systematic search was performed in PubMed, MEDLINE, and EMBASE. We selected studies reporting treatments with flow-diverters in which the device was placed across the ostium of the OphtA, PcomA, or AchorA. Random-effects meta-analysis was used to pool the following outcomes: rate of arterial occlusion, diminished flow, incidence of related symptoms, factors associated with arterial occlusion.
Twenty-one studies evaluating 1152 supraclinoid ICA branches were included in the meta-analysis. The incidence of OphtA occlusion and associated symptoms was 5.9% (95 CI% = 3.1–8.6%) (incidence rate = 6% per patient-year), and 0.8% (95% CI = 0.1–1.4%) (incidence rate = 0.8% per patient-year), respectively. Although asymptomatic in all cases, PcomA showed a higher occlusion rate (20.7%, 95% CI = 8.9–32.4%) (incidence rate = 19.5% per patient-year). AchorA was occluded in 1% (95% CI = 0.3–2.4%) of cases, with approximately 1% (95% CI = 0.4–2.3%) of transient neurological symptoms (incidence rate = 0.96% per patient-year). There was a trend toward higher odds of arterial patency among arteries arising from the aneurysm (OR = 2.94, P = 0.06). Demographic factors and multiple stents were not associated with higher risk of arterial impairment. Adequate collateral circulation was reported in 94.5% of patients with arterial occlusion.
During aneurysm treatment, the ostium of the supraclinoid ICA branches can be covered with flow-diverter devices with low rates of neurological symptoms related to arterial occlusion.
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