Publications by authors named "Luca Triggiani"

63 Publications

Impact of Gastrointestinal Side Effects on Patients' Reported Quality of Life Trajectories after Radiotherapy for Prostate Cancer: Data from the Prospective, Observational Pros-IT CNR Study.

Cancers (Basel) 2021 Mar 23;13(6). Epub 2021 Mar 23.

Radiation Oncology Department, University and Spedali Civili Hospital, 25123 Brescia, Italy.

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients' reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04-7.08; OR = 2.17, 95% CI 1.22-3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06-2.67; OR = 2.57, 95% CI 1.70-3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects.
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http://dx.doi.org/10.3390/cancers13061479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004900PMC
March 2021

OLIGO-AIRO: a national survey on the role of radiation oncologist in the management of OLIGO-metastatic patients on the behalf of AIRO.

Med Oncol 2021 Mar 24;38(5):48. Epub 2021 Mar 24.

Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Negrar, Verona, Italy.

In the last years, several evidences demonstrated the role of stereotactic body radiotherapy (SBRT) in the oligometastatic disease and the possibility to increase survival in selected patients. In 2020 the study group "biology and treatment of the oligometastatic disease" of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey evaluating the attitude of physicians in treating the oligometastatic disease and the definition of it. An electronic questionnaire was administered online to the society members. 105 questionnaires were returned. 78% responders considered as oligometastatic a disease with ≤ 5 metastases. The majority of the responders (77%) treated > 50 patients in the last year, and 89% responders agreed in considering every oligometastatic tumor susceptible to local treatments. Regarding the clinical management of the oligometastatic disease, the majority of the responders (66%) suggested an interdisciplinary discussion. When choosing a treatment option for fit patients with a single oligometastatic focus, 52% of the responders agreed in proposing only SBRT. In the case of unfit patients with a single oligometastatic lesion the agreement was in favor of the SBRT alone (89%). In the oligoprogressive setting, 41% responders opted to continue the current systemic treatment and to add SBRT, while in the case of oligoresidual disease, 70% responders was in favor of adding SBRT and continuing the current systemic treatment. In conclusions, the survey illustrated the current agreement and prescribing attitude for oligometastatic patients in Italy. The non-homogenous agreement in some clinical scenarios suggest the need of more robust evidence.
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http://dx.doi.org/10.1007/s12032-021-01493-yDOI Listing
March 2021

Changes in body composition and lipid profile in prostate cancer patients without bone metastases given Degarelix treatment: the BLADE prospective cohort study.

Prostate Cancer Prostatic Dis 2021 Mar 15. Epub 2021 Mar 15.

Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, Brescia, Italy.

Background: Luteinizing hormone-releasing hormone (LHRH)-agonists in prostate cancer (PCa) patients induce sarcopenic obesity. The effect of LHRH-antagonist on body composition has never been explored. We evaluated changes in fat (FBM) and lean body mass (LBM) in PCa patients undergoing Degarelix.

Methods: This is a single-center prospective study, enrolling 29 non-metastatic PCa patients eligible to LHRH-antagonist from 2017 to 2019. All patients received monthly subcutaneous injection of Degarelix for 12 months. Changes in FBM and LBM between baseline and 12-month Degarelix, as measured by dual-energy x-ray absorptiometry, were the co-primary endpoints. Secondary endpoints were changes in serum lipids, glucose profile and follicle-stimulating hormone (FSH). Appendicular lean mass index (ALMI) and ALMI/FBM ratio were assessed as post-hoc analyses. Linear mixed models with random intercept tested for estimated least squared means differences (EMD).

Results: FBM significantly increased after 12 months (EMD +2920.7, +13.8%, p < 0.001), whereas LBM remained stable (EMD -187.1, -0.3%, p = 0.8). No differences occurred in lipid profile. Glycated hemoglobin significantly increased and serum FSH significantly decreased. A significant inverse relationship was found between serum FSH and ALMI/FBM ratio after 12 month (r = -0.44, p = 0.02).

Conclusions: The BLADE study prospectively evaluated changes in body composition after LHRH-antagonist. LHRH-antagonist therapy is associated to an increased risk of obesity and diabetes, but lean body mass and serum lipids are not affected. This may represent an additional evidence supporting the reduced cardiovascular risk associated with LHRH-antagonist. The role of FSH in influencing sarcopenic obesity in PCa after androgen deprivation deserves to be further explored.
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http://dx.doi.org/10.1038/s41391-021-00345-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958940PMC
March 2021

Caveolin-1 promotes radioresistance in rhabdomyosarcoma through increased oxidative stress protection and DNA repair.

Cancer Lett 2021 May 18;505:1-12. Epub 2021 Feb 18.

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address:

The aim of this work was to investigate whether Caveolin-1 (Cav-1), a membrane scaffolding protein widely implicated in cancer, may play a role in radiation response in rhabdomyosarcoma (RMS), a pediatric soft tissue tumor. For this purpose, we employed human RD cells in which Cav-1 expression was stably increased via gene transfection. After radiation treatment, we observed that Cav-1 limited cell cycle arrest in the G2/M phase and enhanced resistance to cell senescence and apoptosis via reduction of p21, p16 and Caspase-3 cleavage. After radiotherapy, Cav-1-mediated cell radioresistance was characterized by low accumulation of H2AX foci, as confirmed by Comet assay, marked neutralization of reactive oxygen species (ROS) and enhanced DNA repair via activation of ATM, Ku70/80 complex and DNA-PK. We found that Cav-1-overexpressing RD cells, already under basal conditions, had higher glutathione (GSH) content and greater catalase expression, which conferred protection against acute treatment with hydrogen peroxide. Furthermore, pre-treatment of Cav-1-overexpressing cells with PP2 or LY294002 compounds restored the sensitivity to radiation treatment, indicating a role for Src-kinases and Akt pathways in Cav-1-mediated radioresistance. These findings were confirmed using radioresistant RD and RH30 lines generated by hypofractionated radiotherapy protocol, which showed marked increase of Cav-1, catalase and Akt, and sensitivity to PP2 and LY294002 treatment. In conclusion, these data suggest that concerted activity of Cav-1 and catalase, in cooperation with activation of Src-kinase and Akt pathways, may represent a network of vital mechanisms that allow irradiated RMS cells to evade cell death induced by oxidative stress and DNA damage.
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http://dx.doi.org/10.1016/j.canlet.2021.02.005DOI Listing
May 2021

Health-related quality of life 24-month after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

Minerva Urol Nefrol 2021 Jan 13. Epub 2021 Jan 13.

Urology Unit, Azienda Socio-Sanitaria Territoriale Lariana, Sant'Anna Hospital, Como, Italy.

Background: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study.

Methods: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), radiotherapy plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain.

Results: Overall, 1 537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, p<0.001 and - 19.7, p<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, p=0.02) and RT plus ADT groups at 12 months (-10.3, p=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, p<0.001, -37.8, p<0.001, -20.4, p<0.001, respectively).

Conclusions: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.
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http://dx.doi.org/10.23736/S0393-2249.20.04032-1DOI Listing
January 2021

Radiotherapy for the treatment of solitary plasmacytoma: 7-year outcomes by a mono-institutional experience.

J Cancer Res Clin Oncol 2020 Nov 17. Epub 2020 Nov 17.

Department of Radiation Oncology, Brescia University, Piazza Spedali Civili,1, 25100, Brescia, Italy.

Objectives: Solitary plasmacytoma (SP) is characterized by a single mass of clonal plasma cells. Definitive RT can result in long-term local control of the SP. Due to the small number of patients and narrow range of doses, phase III randomized trials are lacking. The aim of this study is to further support the potential use of RT for the treatment of SP.

Methods: Clinical data of all patients treated for SP at our Institution between 1992 and 2018 were reviewed. A total of 42 consecutive patients were analyzed.

Results: The median follow-up was 84.8 months. Radiation dose did not differ significantly as a function of sex, type of SP (solitary bone plasmacytoma or as extramedullary plasmacytoma), tumor size; conversely differs significantly as a function of age (p = 0.04). The 5y-OS and 10y-OS were, respectively, 96 and 91%. Local recurrences developed in 21.4% of patients (9/42). 16 patients progressed to MM (38.1%). The 5y-progression to MM free survival (PMFS) and the 10y-PMFS were, respectively, 68.6 and 61.9%.

Conclusions: Our data confirm that good results are achievable with RT to treat SP, but they don't allow defining a dose-effect correlation; therefore, it remains uncertain which is the most effective dose and whether lower doses can guarantee adequate disease control.
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http://dx.doi.org/10.1007/s00432-020-03452-yDOI Listing
November 2020

Metastasis-directed Therapy (SBRT) Guided by PET-CT F-CHOLINE Versus PET-CT Ga-PSMA in Castration-sensitive Oligorecurrent Prostate Cancer: A Comparative Analysis of Effectiveness.

Clin Genitourin Cancer 2020 Aug 6. Epub 2020 Aug 6.

Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy; Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.

Background: The present analysis aims to compare the impact of 18F-fluorocholine (F-choline) and gallium-68 prostate-specific membrane antigen (Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)-guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC).

Materials And Methods: Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by F-choline or Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered.

Results: A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET-guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with Ga-PSMA-based SBRT.

Conclusion: In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the F-choline-PET cohort. Randomized trials are advocated.
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http://dx.doi.org/10.1016/j.clgc.2020.08.002DOI Listing
August 2020

A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients.

Sci Rep 2020 08 12;10(1):13589. Epub 2020 Aug 12.

Department of Radiation Oncology, Brescia University, Piazzale Spedali Civili, 1, 25123, Brescia, Italy.

Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3-4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3-4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.
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http://dx.doi.org/10.1038/s41598-020-70430-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423932PMC
August 2020

Two months of radiation oncology in the heart of Italian "red zone" during COVID-19 pandemic: paving a safe path over thin ice.

Radiat Oncol 2020 Aug 10;15(1):191. Epub 2020 Aug 10.

Department of Radiation Oncology, Brescia University, Università degli Studi di Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.

Background: Coronavirus Disease 2019 (COVID-19) pandemic had an overwhelming impact on healthcare worldwide. Outstandingly, the aftermath on neoplastic patients is still largely unknown, and only isolated cases of COVID-19 during radiotherapy have been published. We will report the two-months experience of our Department, set in Lombardy "red-zone".

Methods: Data of 402 cancer patients undergoing active treatment from February 24 to April 24, 2020 were retrospectively reviewed; several indicators of the Department functioning were also analyzed.

Results: Dedicated measures allowed an overall limited reduction of the workload. Decrease of radiotherapy treatment number reached 17%, while the number of administration of systemic treatment and follow up evaluations kept constant. Conversely, new treatment planning faced substantial decline. Considering the patients, infection rate was 3.23% (13/402) and mortality 1.24% (5/402). Median age of COVID-19 patients was 69.7 years, the large majority were male and smokers (84.6%); lung cancer was the most common tumor type (61.5%), 84.6% of subjects were stage III-IV and 92.3% had comorbidities. Remarkably, 92.3% of the cases were detected before March 24. Globally, only 2.5% of ongoing treatments were suspended due to suspect or confirmed COVID-19 and 46.2% of positive patients carried on radiotherapy without interruption. Considering only the last month, infection rate among patients undergoing treatment precipitated to 0.43% (1/232) and no new contagions were reported within our staff.

Conclusions: Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during SARS-Cov-2 pandemic by endorsing consistent preventive measures.
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http://dx.doi.org/10.1186/s13014-020-01631-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416803PMC
August 2020

Non-metastatic ductal adenocarcinoma of the prostate: pattern of care from an uro-oncology multidisciplinary group.

World J Urol 2020 Jun 26. Epub 2020 Jun 26.

Urology Unit, Department of Medical and Surgical Specialties, Radiological Science and Public Health, ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy.

Purpose: To retrospectively review our 20 year experience of multidisciplinary management of non-metastatic ductal prostate cancer (dPC), a rare but aggressive histological subtype of prostate cancer whose optimal therapeutic approach is still controversial.

Methods: Histologically confirmed dPC patients undergoing primary, curative treatment [radical prostatectomy (RP), external beam radiotherapy (EBRT), and androgen deprivation therapy (ADT)] were included, and percentage of ductal and acinar pattern within prostate samples were derived. Survival outcomes were assessed using the subdistribution hazard ratio (SHR) and Fine-and-Gray model.

Results: From January 1997 to December 2016, 81 non-metastatic dPC fitted selection criteria. Compared to surgery alone, SHR for progression-free survival and cancer-specific mortality were 2.8 (95% CI 0.6-13.3) and 1.3 (95% CI 0.1-16.2) for exclusive EBRT, 2.7 (95% CI 0.6-13.0) and 6.5 (95% CI 0.6-69.8) for adjuvant EBRT, 4.9 (95% CI 0.7-35.5) and 5.8 (95% CI 0.5-65.6) for salvage EBRT post-prostatectomy recurrence, and 3.2 (95% CI 0.7-14.0) and 3.9 (95% CI 0.3-44.1) for primary ADT (P = 0.558; P = 0.181), respectively. Comparing multimodal treatment and monotherapy confirmed the above trends. Local recurrence more typically occurred in pure dPC patients, mixed histology more frequently produced metastatic spread (29.6% relapse in total, P = 0.026).

Conclusion: Albeit some limitations affected the study, our findings support the role of local treatment to achieve better disease control and improve quality of life. Different behavior, with typical local growth in pure dPC, higher distant metastatization in the mixed form, might influence treatment response. Given its poor prognosis, we recommend multidisciplinary management of dPC.
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http://dx.doi.org/10.1007/s00345-020-03315-8DOI Listing
June 2020

PROLAPSE: survey about local prostate cancer relapse salvage treatment with external beam re-irradiation: results of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

J Cancer Res Clin Oncol 2020 Sep 24;146(9):2311-2317. Epub 2020 Jun 24.

Advanced Radiation Oncology Department, Cancer Care Center, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy.

Purpose: We herein present the results of the first Italian Association of Radiotherapy and Clinical Oncology (AIRO) survey regarding salvage external beam re-irradiation of local prostate cancer relapse named PROLAPSE.

Methods: A questionnaire with 12 items was administered to the 775 Italian radiation oncologist members of the AIRO.

Results: One hundred of the members completed the survey. The survey highlighted that 59% of the participants are currently performing prostate re-EBRT, while nearly two-thirds (65%) affirmed that they are taking into consideration the procedure in case of intraprostatic relapse. Regarding the clinical target volume (CTV), only a minority (16%) declared to always prefer the partial prostate re-irradiation, while a consistent portion (nearly two-thirds) relied on clinical considerations of the choice towards partial or whole gland irradiation. The main techniques used for re-irradiation resulted to be intensity-modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) and SBRT, having received approximately 40% of responses each. Regarding the criteria for patients' selection, more than 75% of responders agreed on the use of positron emission tomography (PET)/computed tomography (CT)-choline to exclude distant metastases and of multiparametric magnetic resonance imaging (mp-MRI) to detect intraprostatic recurrence. A sufficient timeframe (> 3 years) between primary RT and reirradiation was indicated by more than half of participants as an important driver in decision-making, while histological confirmation of the relapse was considered not essential by more than two-thirds. For the use of concomitant androgen deprivation therapy (ADT), most AIRO members (79%) agreed that the prescription should be based on a case-by-case analysis. Extreme hypofractionation (> 5 Gy/fraction) was preferred by the majority (52%) of the AIRO members. In most centers (more than 74%), the planning dose-volume constraints were generally extrapolated from the published data. In half of the cases, the interviewed responders affirmed that no major gastrointestinal (GI) and genitourinary (GU) toxicities were registered in the follow-up of their re-EBRT patients. Bladder complications represented the most commonly observed form of toxicity, with an incidence of 67%.

Conclusion: This first AIRO survey about salvage prostate re-EBRT provides an interesting snapshot and suggests increasing interest in re-EBRT patients in Italy. Consensus about some aspects of patients' selection, the necessity of biopsy, fractionation, and highly selective techniques seems feasible, but other key points such as irradiated volume, dosimetry parameters, and hormonal treatment association need to be clarified.
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http://dx.doi.org/10.1007/s00432-020-03297-5DOI Listing
September 2020

When Less Is More: Specific Capture and Analysis of Tumor Exosomes in Plasma Increases the Sensitivity of Liquid Biopsy for Comprehensive Detection of Multiple Androgen Receptor Phenotypes in Advanced Prostate Cancer Patients.

Biomedicines 2020 May 22;8(5). Epub 2020 May 22.

Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy.

We evaluated the advantages and the reliability of novel protocols for the enrichment of tumor extracellular vesicles (EVs), enabling a blood-based test for the noninvasive parallel profiling of multiple androgen receptor ( gene alterations. Three clinically relevant variants related to response/resistance to standard-of-care treatments (-V7 transcript, T878A point mutation and gene amplification) were evaluated by digital PCR in 15 samples from patients affected by Castration-Resistant Prostate Cancer (CRPC). Plasma was processed to obtain circulating RNA and DNA using protocols based on tumor EVs enrichment through immuno-affinity and peptide-affinity compared to generic extraction kits. Our results showed that immuno-affinity enrichment prior to RNA extraction clearly outperforms the generic isolation method in the detection of -V7, also allowing for a distinction between responder (R) and non-responder (NR) patients. The T878A mutation was detected, overall, in nine out of 15 samples and no approach alone was able to reveal mutations in all harboring samples, showing that the employed methods complement each other. amplification was detected in the majority of CRPC samples analysed using either cell-free DNA (cfDNA) or exosome isolation kits (80%). We demonstrated that selective isolation of a subset of circulating exosomes enriched for tumor origin, rather than analysis of total plasma exosomes, or total plasma nucleic acids, increases sensitivity and specificity for the detection of specific alterations.
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http://dx.doi.org/10.3390/biomedicines8050131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277361PMC
May 2020

A simplified integrated molecular and immunohistochemistry-based algorithm allows high accuracy prediction of glioblastoma transcriptional subtypes.

Lab Invest 2020 10 13;100(10):1330-1344. Epub 2020 May 13.

Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Glioblastomas (GBM) can be classified into three major transcriptional subgroups (proneural, mesenchymal, classical), underlying different molecular alterations, prognosis, and response to therapy. However, transcriptional analysis is not routinely feasible and assessment of a simplified method for glioblastoma subclassification is required. We propose an integrated molecular and immunohistochemical approach aimed at identifying GBM subtypes in routine paraffin-embedded material. RNA-sequencing analysis was performed on representative samples (n = 51) by means of a "glioblastoma transcriptional subtypes (GliTS) redux" custom gene signature including a restricted number (n = 90) of upregulated genes validated on the TCGA dataset. With this dataset, immunohistochemical profiles, based on expression of a restricted panel of gene classifiers, were integrated by a machine-learning approach to generate a GliTS based on protein quantification that allowed an efficient GliTS assignment when applied to an extended cohort (n = 197). GliTS redux maintained high levels of correspondence with the original GliTS classification using the TCGA dataset. The machine-learning approach designed an immunohistochemical (IHC)-based classification, whose concordance was 79.5% with the transcriptional- based classification, and reached 90% for the mesenchymal subgroup. Distribution and survival of GliTS were in line with reported data, with the mesenchymal subgroup given the worst prognosis. Notably, the algorithm allowed the identification of cases with comparable probability to be assigned to different GliTS, thus falling within overlapping regions and reflecting an extreme heterogeneous phenotype that mirrors the underlying genetic and biological tumor heterogeneity. Indeed, while mesenchymal and classical subgroups were well segregated, the proneural types frequently showed a mixed proneural/classical phenotype, predicted as proneural by the algorithm, but with comparable probability of being assigned to the classical subtype. These cases, characterized by concomitant high expression of EGFR and proneural biomarkers, showed lower survival. Collectively, these data indicate that a restricted panel of highly sensitive immunohistochemical markers can efficiently predict GliTS with high accuracy and significant association with different clinical outcomes.
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http://dx.doi.org/10.1038/s41374-020-0437-0DOI Listing
October 2020

Cetuximab and Radiation Therapy Versus Cisplatin and Radiation Therapy for Locally Advanced Head and Neck Cancer: Long-Term Survival and Toxicity Outcomes of a Randomized Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2020 07 14;107(3):469-477. Epub 2020 Mar 14.

Radiation Oncology Department, ASST Spedali Civili di Brescia - Brescia University, Brescia, Italy.

Purpose: This study describes the long-term survival and toxicity outcomes of a multicenter randomized phase 2 trial comparing radiation therapy (RT) plus cisplatin (CDDP) or cetuximab (CTX) as first line treatment in locally advanced head and neck cancer (LASCCHN).

Methods And Materials: Between January 2011 and August 2014, 70 patients were enrolled and randomized to receive RT plus weekly CDDP (40 mg/m) or CTX (250 mg/m plus a loading dose of 400 mg/m). This updated series focuses on late toxicities (graded by using Common Terminology Criteria for Adverse Events version 4.0) and long-term survival outcomes in terms of local control, overall survival, cancer-specific survival, and metastasis-free survival (MFS). A supplementary analysis based on human papilloma virus (HPV) status was also performed.

Results: No statistically significant difference was found in terms of late effects (xerostomia, fibrosis, mucosal atrophy, weight loss). In the CDDP arm and the CTX arm, 5-year local control rates were 67% and 48%; 5-year MFS rates were 83% and 97%; 5-year overall survival rates were 61% and 52%; and 5-year cancer-specific survival rates were 70% and 59%, respectively. None of these differences reached statistical significance. A subgroup analysis by HPV status and anatomic subsites revealed that in HPV+ oropharyngeal carcinoma, better survival was obtained in the CDDP arm (although statistical tests were not performed owing to the small sample size). Conversely, no statistically significant differences were observed in HPV- oropharyngeal carcinoma and other anatomic subsites, except for the confirmed better MFS rates of the CTX arm.

Conclusions: Long-term results are in line with current literature suggesting that RT + CTX is inferior to RT + CDDP for the definitive treatment of LASCCHN. However, if not as an alternative to CDDP, CTX might still play a role in LASCCHN, particularly in HPV- cases.
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http://dx.doi.org/10.1016/j.ijrobp.2020.02.637DOI Listing
July 2020

Modeling Acquired Resistance to the Second-Generation Androgen Receptor Antagonist Enzalutamide in the TRAMP Model of Prostate Cancer.

Cancer Res 2020 04 6;80(7):1564-1577. Epub 2020 Feb 6.

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration-resistant prostate cancer (CRPC) in chemotherapy-naïve as well as in patients previously exposed to chemotherapy. However, resistance to enzalutamide and enzalutamide withdrawal syndrome have been reported. Thus, reliable and integrated preclinical models are required to elucidate the mechanisms of resistance and to assess therapeutic settings that may delay or prevent the onset of resistance. In this study, the prostate cancer multistage murine model TRAMP and TRAMP-derived cells have been used to extensively characterize and the response and resistance to enzalutamide. The therapeutic profile as well as the resistance onset were characterized and a multiscale stochastic mathematical model was proposed to link the and evolution of prostate cancer. The model showed that all therapeutic strategies that use enzalutamide result in the onset of resistance. The model also showed that combination therapies can delay the onset of resistance to enzalutamide, and in the best scenario, can eliminate the disease. These results set the basis for the exploitation of this "TRAMP-based platform" to test novel therapeutic approaches and build further mathematical models of combination therapies to treat prostate cancer and CRPC. Merging mathematical modeling with experimental data, this study presents the "TRAMP-based platform" as a novel experimental tool to study the and evolution of prostate cancer resistance to enzalutamide.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-3637DOI Listing
April 2020

A pilot study on the Vanderbilt head and neck symptom survey Italian version (VHNSS-IT) to test its feasibility and utility in routine clinical practice.

Radiol Med 2020 Apr 10;125(4):423-431. Epub 2020 Jan 10.

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: Patient-reported outcome measures can be useful to assess symptoms in head and neck cancer (HNC) patients treated with radio-chemotherapy. This is a pilot study on the VHNSS-IT (the Italian version of the Vanderbilt head and neck symptom survey) performed to assess both the feasibility and utility of its administration in clinical practice.

Methods: The outcomes analyzed were feasibility to recruit patients, feasibility to complete the questionnaire, feasibility to review the questionnaire, utility perceived by clinicians, distribution of patient's answers reflecting symptom's intensity.

Results: Among the 38 patients enrolled, 37 completed the VHNSS-IT (refusal rate 2.6%). Median time of completion was 6'57″. Time of completion was influenced by age (p = 0.002), grade of education (p = 0.023) and employment status (p = 0.004). Time after the start of the radiotherapy course (< 6 months vs. > 6 months) and surgery (yes vs. no) influenced symptoms' intensity. Median time for review was 2'15″. Time burden was perceived to be acceptable for all clinicians; they all also found the questionnaire easy to use. Rates of global perceived utility and future intention to use the questionnaire were 100%.

Conclusions: The VHNSS-IT has demonstrated to be a useful measurement of symptoms' burden for patients with HNC. The survey can be easily completed during the clinic routine without interfering with doctors' visits schedule, and it can help healthcare providers to identify symptoms that require referral, education or intervention.
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http://dx.doi.org/10.1007/s11547-019-01125-6DOI Listing
April 2020

The linguistic validation process of the Vanderbilt Head and Neck Symptom Survey - Italian Version (VHNSS-IT).

Radiol Med 2020 Feb 29;125(2):228-235. Epub 2019 Nov 29.

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: To linguistically validate the Italian translation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), there is a patient-reported outcome measure to screen for symptoms in the head and neck cancer (HNC) patients population. The goal was to ensure conceptually equivalence with the original version and maintain clarity, ease of use and understanding.

Methods: We conducted a multi-step linguistic process (forward translation, backward translation and patient testing) to generate and validate an Italian translation of the VHNSS.

Results: Two intermediate Italian versions were created: The first Italian version was derived from a reconciliation of the three forward translations, and the second Italian version was derived from changes in the first version after the backward translation step. All investigators involved actively discussed possible solutions to produce a translated instrument that maintained a reading and comprehension level accessible by most respondents, without altering the meaning and content of the original source. During the patient testing step, only two patients reported problems with items comprehension and the rate of comprehension problems per single item was lower than expected. This phase allowed patients to give suggestion in order to make items clearer and easier to understand: 43% of patients proposed a revision of the survey during the face-to-face interview, and most of these suggestions were retained.

Conclusions: A valid multi-step process leads to the creation of the final version of the VHNSS-IT, a suitable instrument to screen for symptoms in the Italian HNC patients population and an official measurement tool that can be used in cooperative research group.
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http://dx.doi.org/10.1007/s11547-019-01105-wDOI Listing
February 2020

Treatment paths for localised prostate cancer in Italy: The results of a multidisciplinary, observational, prospective study (Pros-IT CNR).

PLoS One 2019 1;14(11):e0224151. Epub 2019 Nov 1.

Radiation Oncology Department, University and Spedali Civili Hospital, Brescia, Italy.

Background: There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study.

Methods: The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method.

Results: At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis.

Conclusions: An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224151PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824566PMC
March 2020

Cetuximab and Radiation Therapy in Head and Neck Cancer.

Int J Radiat Oncol Biol Phys 2019 11;105(3):678-679

Radiation Oncology Department, ASST Spedali Civili di Brescia - Brescia University, Brescia, Italy.

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http://dx.doi.org/10.1016/j.ijrobp.2019.07.025DOI Listing
November 2019

Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature.

Cancers (Basel) 2019 Aug 31;11(9). Epub 2019 Aug 31.

Department of Radiation Oncology, Brescia University, 25123 Brescia, Italy.

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called "cancer stem cells". Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.
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http://dx.doi.org/10.3390/cancers11091284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769799PMC
August 2019

Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group.

Head Neck 2019 10 29;41(10):3684-3692. Epub 2019 Jul 29.

Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background: To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published.

Methods: We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population.

Results: Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability.

Conclusion: Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population.
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http://dx.doi.org/10.1002/hed.25890DOI Listing
October 2019

Metastasis-directed Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A Multi-institutional Analysis Comparing the Outcome and Toxicity of Stereotactic Body Radiotherapy and Elective Nodal Radiotherapy.

Eur Urol 2019 12 20;76(6):732-739. Epub 2019 Jul 20.

Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium.

Background: Stereotactic body radiotherapy (SBRT) and elective nodal radiotherapy (ENRT) are being investigated as metastasis-directed treatments in oligorecurrent prostate cancer (PC); however, comparative data are still lacking.

Objective: To compare outcome and toxicity between both treatments. Primary endpoint was metastasis-free survival, adjusted for selected variables (aMFS).

Design, Setting, And Participants: This was a multi-institutional, retrospective analysis of 506 (SBRT: 309, ENRT: 197) patients with hormone-sensitive nodal oligorecurrent PC (five or fewer lymph nodes (LNs; N1/M1a), treated between 2004 and 2017. Median follow-up was 36 mo (interquartile range 23-56).

Intervention: SBRT was defined as a minimum of 5 Gy per fraction to each lesion with a maximum of 10 fractions. ENRT was defined as a minimum dose of 45 Gy in up to 25 fractions to the elective nodes, with or without a simultaneous boost to the suspicious node(s). The choice of radiotherapy (RT) was at the discretion of the treating physician, with treatments being unbalanced over the centers.

Outcome Measurements And Statistical Analysis: In total, 506 patients from 15 different treatment centers were included. Primary treatment was radical prostatectomy, RT, or their combination. Nodal recurrences were detected by positron emission tomography/computer tomography (97%) or conventional imaging (3%). Descriptive statistics was used to summarize patient characteristics.

Results And Limitations: ENRT was associated with fewer nodal recurrences compared with SBRT (p < 0.001). In a multivariable analysis, patients with one LN at recurrence had longer aMFS after ENRT (hazard ratio: 0.50, 95% confidence interval 0.30-0.85, p = 0.009). Late toxicity was higher after ENRT compared with that after SBRT (16% vs. 5%, p < 0.01). Limitations include higher use of hormone therapy in the ENRT cohort and nonstandardized follow-up.

Conclusions: ENRT reduces the number of nodal recurrences as compared with SBRT, however at higher toxicity. Our findings hypothesize that ENRT should be preferred to SBRT in the treatment of nodal oligorecurrences. This hypothesis needs to be evaluated in a randomized trial.

Patient Summary: This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal radiotherapy might be the preferred treatment.
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http://dx.doi.org/10.1016/j.eururo.2019.07.009DOI Listing
December 2019

Applying radiation protection and safety in radiotherapy.

Radiol Med 2019 Aug 18;124(8):777-782. Epub 2019 May 18.

Radiation Oncology Department, San Martino Teaching Hospital, Genova University (DISSAL), Genoa, Italy.

Radiotherapy is one of the primary treatment options in cancer management. Modern radiotherapy includes complex processes requiring many different kinds of expertise. Among them, knowledge and skills are needed in clinical oncology, radiobiology, radiotherapy planning and simulation, dose measurement and calculation, radiation safety and medical physics. Radiation oncologists should assume the full and final responsibility for treatment, follow-up and supportive care of the patient. For all these activities, radiation oncologist should coordinate and collaborate with a team including different professionals: nurses, radiographers (RTT), clinical engineers, information system experts, taking advantage in particular of the dosimetry expertise of the medical physicist. Radiation therapy is widely recognized to be one of the safest areas of modern medicine, and errors are very rare. However, radiation protection recommendations developed at national level should comply with the EURATOM Directive 2013/59. This paper describes several contemporary and emerging concerns related to radioprotection in radiation therapy including quality and safety in external beam radiotherapy and brachytherapy, foetal dose, secondary malignancies, and the safety issues related to the new techniques and treatment strategies.
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http://dx.doi.org/10.1007/s11547-019-01043-7DOI Listing
August 2019

Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Crit Rev Oncol Hematol 2019 Jun 1;138:24-28. Epub 2019 Apr 1.

Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy.

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.
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http://dx.doi.org/10.1016/j.critrevonc.2019.03.014DOI Listing
June 2019

Hypofractionated radiation therapy versus chemotherapy with temozolomide in patients affected by RPA class V and VI glioblastoma: a randomized phase II trial.

J Neurooncol 2019 Jul 4;143(3):447-455. Epub 2019 May 4.

Radiation Oncology Department, Brescia University, Piazzale Spedali Civili 1, 23123, Brescia, Italy.

Introduction: In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment regimens in terms of survival and quality of life.

Methods: Patients with histologic diagnosis of glioblastoma were randomized to hypofractionated radiotherapy (RT-30 Gy in 6 fractions) and exclusive chemotherapy (CHT-emozolomide 200 mg/m/day 5 days every 28 days). Overall (OS) and progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors. Quality- adjusted survival (QaS) was evaluated according to the Murray model (Neurological Sign and Symptoms-NSS) RESULTS: From 2010 to 2015, 31 pts were enrolled (CHT: 17 pts; RT: 14pts). Four pts were excluded from the analysis. RPA VI (p = 0.048) and absence of MGMT methylation (p = 0.001) worsened OS significantly. Biopsy (p = 0.048), RPA class VI (p = 0.04) and chemotherapy (p = 0.007) worsened PFS. In the two arms the initial NSS scores were overlapping (CHT: 12.23 and RT: 12.30) and progressively decreased in both group and became significantly worse after 5 months in CHT arm (p = 0.05). Median QaS was 104 days and was significantly better in RT arm (p = 0.01).

Conclusions: The data obtained are limited by the poor accrual. Both treatments were well tolerated. Patients in RT arm have a better PFS and QaS, without significant differences in OS. The deterioration of the NSS score would seem an important parameter and coincide with disease progression rather than with the toxicity of the treatment.
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http://dx.doi.org/10.1007/s11060-019-03175-2DOI Listing
July 2019

Combining abiraterone and radiotherapy in metastatic castration-resistant prostate cancer: a review of current evidence.

Tumori 2019 Aug 25;105(4):277-281. Epub 2019 Mar 25.

4 Department of Radiation Oncology, Policlinico Tor Vergata, University of Rome, Rome, Italy.

Prostate cancer is the second most frequent cancer worldwide, with a very high rate of progression despite treatment. The most aggressive form of the disease is known as castration-resistant prostate cancer, which carries a poor prognosis. We reviewed available literature regarding the combination of abiraterone acetate antihormonal drug and ablative radiation therapy for the treatment of metastatic castration-resistant prostate cancer. This dual treatment may enhance the effects of second-line hormonal therapy, as radiotherapy renders cancer cells more prone to immune-mediated cytotoxicity. Moreover, radiotherapy exerts its effect both on directly irradiated cells and on other distant tissues, with an abscopal effect, already demonstrated in other solid tumors. This combination treatment is safe and effective, with few adverse events. Moreover, it is of paramount importance in patients with oligoprogression of the primary disease, when current guidelines recommend continuing abiraterone treatment. Ablative radiation therapy is a noninvasive, nontoxic treatment with very high efficacy on local tumor growth control. In the available literature, the combination of radiation therapy and abiraterone acetate has prolonged both overall survival and progression-free survival, with a positive impact also on locoregional recurrence and distant metastases.
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http://dx.doi.org/10.1177/0300891619839282DOI Listing
August 2019

Bone metastases from head and neck malignancies: Prognostic factors and skeletal-related events.

PLoS One 2019 20;14(3):e0213934. Epub 2019 Mar 20.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy.

Background: We conducted a multicenter retrospective analysis to describe the characteristics, frequency of skeletal-related events (SREs), and prognosis of head and neck cancer (HNC) in patients with bone metastases (BM).

Patients And Methods: The data of 192 HNC patients with BMs were collected. Analyses were conducted separately in 64 nasopharyngeal cancer (NPC) patients and in 128 non-NPC patients.

Results: SREs occurred in 34 (27%) non-NPC and in 6 (9%) NPC patients, respectively. Median overall survival (OS) was 25 and 6 months in NPC and non-NPC patients, respectively. Locoregional recurrence (hazard ratio [HR] 2.33, 95% confidence interval (CI) 1.1-4.93), synchronous BM (HR 0.25, 95% CI 0.59-0.71) and bone-directed therapies (BDT) (HR 0.26, 95% CI 0.10-0.68) were independent prognostic factors for OS in NPC patients. Combined bone radiotherapy (RT) and BDT in NPC patients obtained longer survival (38 months) than either therapy alone (25 months) or neither of these therapies (8 months).

Conclusions: Patients with BMs from non-NPC have a poor prognosis and are at high risk of SREs. NPC patients with BMs are at relatively low risk of SREs. BDT may potentially improve survival, particularly when combined with bone RT. This last finding deserves prospective confirmation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213934PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426213PMC
December 2019