Purpose
In the present study, the acute toxicity profiles for prostate patients treated with simultaneous integrated boost (SIB) with volumetric modulated arcs in a hypofractionated regime are ...reported.
Patients and methods
A total of 70 patients treated with RapidArc between May 2010 and September 2011 were retrospectively evaluated. Patients were stratified into low (36%), intermediate (49%), and high-risk (16%) groups. Target volumes (expanded to define the planning volumes (PTV)) were clinical target volume (CTV) 1: prostate; CTV2: CTV1 + seminal vesicles; CTV3: CTV2 + pelvic nodes. Low-risk patients received 71.4 Gy to PTV1; intermediate-risk 74.2 Gy to PTV1 and 61.6 or 65.5 Gy to PTV2; high-risk 74.2 Gy to PTV1, 61.6 or 65.5 Gy to PTV2, and 51.8 Gy to PTV3. All treatments were in 28 fractions. The median follow-up was 11 months (range 3.5–23 months). The acute rectal, gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to EORTC/RTOG scales.
Results
Acute toxicities were recorded for the GU G0 = 31/70 (44%), G1 = 22/70 (31%); G2 = 16/70 (23%); G3 = 1/70 (1%), the rectum G0 = 46/70 (66%); G1 = 12/70 (17%); G2 = 12/70 (17%); no G3, and the GI G0 = 54/69 (77%); G1 = 11/69 (16%); G2 = 4/69 (6%); no G3. Median time to rectal, GU, and GI toxicities were 27, 30, and 33 days, respectively. Only the GI toxicity correlated with stage and pelvic irradiation. Univariate analysis presented significant correlations between GI toxicity and intestinal irradiation (V
50 Gy
and V
60 Gy
). In the multivariate analysis, the only significant dosimetric variable was V
50 Gy
for the intestinal cavity.
Conclusion
Moderate hypofractionation with SIB and RapidArc was shown to be safe, with acceptable acute toxicity. Longer follow-up is needed to assess late toxicity and clinical outcome.
Abstract
BACKGROUND
Patients with high-grade gliomas (HGGs) have historically been excluded from immunotherapeutic early-phase clinical trials (ieCTs) due to unavailability of serial bioptic ...sampling, the frequent need of corticosteroids, concerns regarding activity of immunotherapy in central nervous system, and rapid clinical deterioration.
MATERIAL AND METHODS
We retrospectively reviewed data of all recurrent HGG patients enrolled in ieCTs at Humanitas Cancer Center Phase I Unit between 2014 and 2019. Disease control rate (DCR) according to RANO criteria, six-months progression-free and overall survival (PFS-6; OS-6), and treatment-related adverse events (TRAEs), were evaluated. A control-cohort (CC) of patients treated with standard treatments (temozolomide, fotemustine, lomustine and procarbazine, bevacizumab) matched (1:1) for sex, age, line of treatment, MGMT methylation status, and IDH mutational status, was selected for comparison. A series of clinical parameters with an established prognostic value for patients with solid tumors treated into ieCTs were correlated with survivals through an univariate analysis. These include: use of steroids, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, lactate dehydrogenase, albumin, total protein.
RESULTS
Five among the 23 ieCTs conducted at our Phase I Unit allowed inclusion of HGG patients. 25 patients were enrolled in the experimental cohort (EC): 22 (88%) glioblastoma, 3 (12%) anaplastic astrocytoma. Median age was 50 years (range 25–71); 16 patients (64%) were men, 9 (36%) women; 17 pts (68%) required steroid therapy, with a median baseline dexamethasone dose of 2 mg (range 1–6). The median number of prior systemic therapies was 1 (range 1–2). Twelve patients (48%) received monotherapies (anti PD-1, anti CSFR-1, anti TGF-ß, anti cereblon), 13 (52%) combination regimens (anti PD-L1 + anti CD38, anti PD-1 + anti CSFR-1). DCR was 40% (1 CR + 2 PR + 7 SD) and 37% (9 SD), in EC and CC, respectively. Four patients (16%) in EC had grade ≥3 TRAEs (1 neutropenia, 1 pneumonia, 2 hepatitis). With a median follow-up of 14 months PFS-6 were 35% and 16% (p=0.075), in EC and CC respectively, while OS-6 was significantly improved in the EC (82% vs 44%, p=0.004). In our small series, none of clinical factors resulted prognostic.
CONCLUSION
Survival outcomes of ourHGG patients treated into ieCTs compared very favorably with a matched CC. Inclusion of HGGs patients into ieCTs should be strongly encouraged. Identification of clinical factors to select who may benefit from ieCTs still remains crucial.
Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we ...retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.
Abstract
Background
Primary cardiac sarcomas (PCS) have a dismal prognosis (a reported median survival of 17 months). Complete surgical resection is the mainstay of treatment, but the resection may ...be incomplete or impossible because of the local extension. Multimodal treatment (MMT) with chemotherapy and radiotherapy (RT) is widely used in soft tissue sarcomas of the extremities, improving survival, and could be considered for PCS. A consequence of the inclusion of the heart in a radiation field, is acute and chronic radiation-induced heart disease (RIHD). New RT techniques, as Intensity Modulated Radiotherapy (IMRT) reduce the risk, focusing the radiation burden to the target neoplasm and limiting the involvement of the cardiac structures. Nevertheless, RT is rarely used in PCS, because the target lesion is inside the heart, and the heart's movement make difficult to avoid the irradiation of the surrounding structures.
Purpose
Our aim was to report the short and long term clinical and echocardiographic changes in patients (pts) with cardiac sarcomas treated with IMRT.
Methods
Amongst a group of 33 with PCS seen in our hospitals, we reviewed the data of 20 pts (12 males, 8 females) with PCS treated with local RT. The tumors were left-sided in 10 pts, right-sided in 8 and involved both right and left chambers in 2; fifteen patients had received also anthracyclines chemotherapy (CT). For every patient, we reviewed the clinical data and the echocardiograms performed (as for protocol) before and after CT, before starting RT, weekly during RT and at follow-up (FU), performed every 3 months for 2 years, every 6 months for 3 more years, then yearly. The mean age at diagnosis was 48 years (range 22–72). The FU lasted 2 to 131 months (mean 31, median 14). Five pts are alive 29–85 months (mean 57), after ending therapies, the others died of non-cardiac causes.
Results
At the end of RT 3 pts had atrial fibrillation (AF), which was cardioverted with Amiodarone, and one had acute pericarditis, treated with non-steroidal anti-inflammatory drugs for one week. Long-term therapy was not needed. The left ventricular ejection fraction (LVEF) was 52% to 70%, decreased by −1% to −10% in 10 pts. At last FU, LVEF ranged from 52 to 75%; it decreased (compared to baseline) by >11% in 1 pt only; global longitudinal LV strain (GLS), available in 8 pts only, was −17%. Amongst the pts with IMRT on the right heart, right ventricular function (evaluated by tricuspid annulus excursion, and right ventricular area shortening fraction) was within normal limits in all both at short and long term FU. There were no cases of constrictive pericarditis or of valvular disease.
Conclusion
In our experience IMRT for heart sarcomas seems to be relatively safe using modern RT techniques, without evident RIHD at long term follow-up. Larger studies are necessary to further evaluate the safety of RT in the multimodal treatment of cardiac sarcomas.
Abstract
Background
Meningioma is the most common primary intracranial tumor, accounting for approximately 15–30% of primary brain tumors. Skull base meningiomas, represent a subgroup of tumors in ...which a complete surgical removal is rarely achieved and the amount of surgical resection represents a crucial factor influencing the risk of recurrence. The role of adjuvant radiotherapy (RT) is still unclear and evidence is lacking. The aim of the present study was to evaluate prognostic factors influencing the local recurrence rate in a large series of grade I-II skull base meningiomas treated with surgery followed by RT in selected cases. Local toxicity, patients symptoms relief and local control rate were evaluated as well.
Material and Methods
Newly diagnosed skull base meningiomas underwent surgery, were included. The extent of surgical resection (EOR) was defined according to Simpson criteria, and were dichotomized as gross total resection (GTR) and subtotal resection (STR). Adjuvant RT was considered in case of STR. Clinical outcome was evaluated by neurological examination and brain MRI performed every 6 months for the first year and yearly thereafter. The 30-days postoperative morbidity and mortality were recorded.
Results
From January 2000 to December 2015, 142 patients were analyzed. The majority were female (69.1%), with a KPS ≥80 (95.8%), grade I meningioma(86.6%), and symptoms at diagnosis (92.3%). STR was performed in 69.7%, followed by adjuvant RT in 15%. Improvement or stability of neurological status was obtained in 78.9% of patients. The median follow-up time was 71 months (range 24–214 months). Local recurrence occurred in 43 (30.3%) patients at a median time of 32 months (range 6–199 months). No patients who underwent surgery plus adjuvant RT had local relapse. The median PFS was 172 months (95%CI 144–193 months), and the 2,5,10-year PFS were 87.9%(±2.8%), 78.2%(±3.8%) and 65.1%(±5.6%), respectively. The 2, 5, 10-year OS were (median not reached) 98.6% (±0.9%),96.7% (±1.6%), and 94.4% (±2.7%), respectively. On univariate analysis factors identified as significantly impacting PFS were the EOR (p value<0.01), the combined treatment, surgery plus RT (p value<<0.01), and the meningioma grade (p value <0.01). The combined treatments was confirmed on multivariate too (p value <<0.01).
Conclusion
Overall, our findings suggest that recurrence rates are influenced by WHO meningiomas grade, the extent of surgical resection, and the employ of adjuvant RT in not completely resected meningioma, regardless of tumor grade. Local control and durability of results suggest for a routine application of this approach in properly selected cases.
Production of neutrinos is abundant at LHC. Flavour composition and energy reach of the neutrino flux from proton-proton collisions depend on the pseudorapidity \(\eta\). At large \(\eta\), energies ...can exceed the TeV, with a sizeable contribution of the \(\tau\) flavour. A dedicated detector could intercept this intense neutrino flux in the forward direction, and measure the interaction cross section on nucleons in the unexplored energy range from a few hundred GeV to a few TeV. The high energies of neutrinos result in a larger \(\nu\)N interaction cross section, and the detector size can be relatively small. Machine backgrounds vary rapidly while moving along and away from the beam line. Four locations were considered as hosts for a neutrino detector: the CMS quadruplet region (~25 m from CMS Interaction Point (IP)), UJ53 and UJ57 (90 and 120 m from CMS IP), RR53 and RR57 (240 m from CMS IP), TI18 (480 m from ATLAS IP). The potential sites are studied on the basis of (a) expectations for neutrino interaction rates, flavour composition and energy spectrum, (b) predicted backgrounds and in-situ measurements, performed with a nuclear emulsion detector and radiation monitors. TI18 emerges as the most favourable location. A small detector in TI18 could measure, for the first time, the high-energy \(\nu\)N cross section, and separately for \(\tau\) neutrinos, with good precision, already with 300 fb\(^{-1}\) in the LHC Run3.
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