Publications by authors named "Marco Krengli"

127 Publications

Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study.

Eur J Cancer 2021 Apr 6;150:190-202. Epub 2021 Apr 6.

Policlinico Universitario Campus Bio-Medico, Rome, Italy.

Background: Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU.

Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19-specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes in multivariable Cox regression models.

Findings: Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard ratio [HR], 1.64 [95% confidence interval {CI}, 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33-1.88]). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti-COVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy after COVID-19 were similar in the UK and EU cohorts.

Interpretation: UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted.
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http://dx.doi.org/10.1016/j.ejca.2021.03.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023206PMC
April 2021

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR ( = 0.030 and = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS ( = 0.050) and was significantly associated with lower EFS ( = 0.030) and histological grade 3 with a lower LC ( = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.
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http://dx.doi.org/10.3390/cancers13081902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071256PMC
April 2021

Psychotherapy with Music Intervention Improves Anxiety, Depression and the Redox Status in Breast Cancer Patients Undergoing Radiotherapy: A Randomized Controlled Clinical Trial.

Cancers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Physiology Laboratory, Department of Translational Medicine, University of "Piemonte Orientale", Via Solaroli 17, 28100 Novara, Italy.

The aim of this study was to assess the effects of psychotherapy with music intervention (PMI) on anxiety, depression, redox status, and inflammation in breast cancer patients undergoing radiotherapy (RT). This monocentric randomized clinical trial recruited 60 patients who had a breast cancer operation and were undergoing postoperative RT. Eligible patients were randomized (1:1) in two groups: the control group (CG) received treatment as usual ( = 30), i.e., RT alone; the intervention group (PMI) received RT and psychotherapy with music intervention ( = 30), which was delivered in a group setting. Five patients were excluded after randomization. Assessments were performed at baseline (T0), at the end of RT (T1), and three months after the end of RT (T2). The main objectives of the study were the assessment of anxiety/depression, plasma glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in the two arms of the study. Our findings revealed a positive effect of PMI on anxiety, depression, resilience, and quality of life. Furthermore, a positive effect of PMI on redox status was found for the first time. Thus, in the PMI group, we found a significant increase of GSH (mean change 2.2 95%, CI 0.7 to 3.7) and a significant reduction of TBARS (mean change -1.1 95%, CI -1.8 to -0.3) at T2 vs. T0.
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http://dx.doi.org/10.3390/cancers13081752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067630PMC
April 2021

Macrophages expressing TREM-1 are involved in the progression of HPV16-related oropharyngeal squamous cell carcinoma.

Ann Med 2021 Dec;53(1):541-550

Pathology Unit, Ospedale "Sant'Andrea", DiMeT, University of Piemonte Orientale (UPO), Vercelli, Italy.

Introduction: Many types of research have been performed to improve the diagnosis, therapy, and prognosis of oropharyngeal carcinomas (OP-SCCs). Since they arise in lymphoid-rich areas and intense lymphocytic infiltration has been related to a better prognosis, a TREM-1 putative function in tumour progression and survival has been hypothesized.

Materials And Methods: Twenty-seven human papillomavirus (HPV) 16 OP-SCC specimens have been analyzed to relate TREM-1 expression with histiocytic and lymphocytic markers, HPV presence and patients' outcome.

Results: No differences have been shown between intratumoral and stromal CD4 cells, while intratumoral CD8 lymphocytes are higher with respect to the tumour stroma (=.0005). CD68 cells are more than CD35 and TREM-1; their presence is related to CD35 and TREM-1 histiocytes (=.005 and .026, respectively). Intratumoral CD4 lymphocytes are higher in p16 cases (11/27) than in p16 (=.042); moreover, p16 positivity correlates to a better survival (=.034). CD4, CD8 and CD35 cells have no impact on survival, while CD68 expression heavily influences progression and bad outcome (=.037). TREM-1 positivity also leads to worst overall survival (=.001): peritumoral expression and death-cause relationship are always significant, particularly when the cause is OP-SCC (=.000).

Conclusion: While p16 shows to better stratify HPV16 patients' outcome, TREM-1 macrophages suggest their key importance in HPV-related OP-SCCs progression.KEY MESSAGESTREM-1 positivity correlates to the worst overall survival of HPV16-positive OPSCCs-affected patients.p16-positive HPV16 related OPSCCs patients have a better prognosis with respect to p16-negative ones.
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http://dx.doi.org/10.1080/07853890.2021.1905872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008925PMC
December 2021

Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19.

J Thromb Thrombolysis 2021 Mar 1. Epub 2021 Mar 1.

Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy.

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.
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http://dx.doi.org/10.1007/s11239-021-02401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919624PMC
March 2021

Post-operative management of brain metastases: GRADE-based clinical practice recommendations on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

J Cancer Res Clin Oncol 2021 Mar 23;147(3):793-802. Epub 2021 Jan 23.

Department of Radiation Oncology, Policlinico S. Gerardo and University of Milan "Bicocca", Milan, Italy.

Purpose: To perform a systematic review of the current level of evidence on post-operative management following brain metastasectomy (namely: adjuvant stereotactic radiosurgery, whole brain radiotherapy or observation), and to propose a GRADE-based dedicated recommendation to inform Radiation Oncologists' clinical practice.

Methods: A panel of expert Radiation Oncologists from the Italian Association of Radiotherapy and Clinical Oncology had defined the search question per the PICO methodology. Electronic databases were independently screened; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was adopted. The individual and pooled hazard ratios with 95% confidence intervals (CI), as well as the pooled risk ratio (RR) were calculated using a fixed- or random-effects model.

Results: Eight full-texts were retrieved: six retrospective studies and two randomized clinical trials. Outcomes of benefit and damage were analyzed for SRS + observation (PICO A) and SRS + WBRT. SRS allowed for increased rates of local control when compared to both observation and WBRT, while evidence was less conclusive for distant brain control, leptomeningeal disease control and overall survival. In the SRS, the incidence of severe radionecrosis was higher as compared to WBRT, despite neurocognitive deterioration rates were lower. Overall, SRS seems to favorably compare with observation and whole brain RT, despite the level of evidence for the recommendation was low and very low, respectively.

Conclusion: Despite low level of evidence, the panel concluded that the risk/benefit ratio probably favors adjuvant SRS as compared to the observation and whole brain RT as adjuvant treatments following brain metastasectomy (5 votes/5 participants, 100% attendance).
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http://dx.doi.org/10.1007/s00432-021-03515-8DOI Listing
March 2021

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients.

Sci Rep 2020 11 26;10(1):20731. Epub 2020 Nov 26.

Department of Translational Medicine, Università del Piemonte Orientale UPO, Via Solaroli 17, 28100, Novara, NO, Italy.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO/FiO ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.
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http://dx.doi.org/10.1038/s41598-020-77698-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692524PMC
November 2020

AKR1C3 is a biomarker and druggable target for oropharyngeal tumors.

Cell Oncol (Dordr) 2021 Apr 19;44(2):357-372. Epub 2020 Nov 19.

Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy.

Purpose: Oropharynx squamous cell carcinoma (OPSCC) is a subtype of head and neck squamous cell carcinoma (HNSCC) arising from the base of the tongue, lingual tonsils, tonsils, oropharynx or pharynx. The majority of HPV-positive OPSCCs has a good prognosis, but a fraction of them has a poor prognosis, similar to HPV-negative OPSCCs. An in-depth understanding of the molecular mechanisms underlying OPSCC is mandatory for the identification of novel prognostic biomarkers and/or novel therapeutic targets.

Methods: 14 HPV-positive and 15 HPV-negative OPSCCs with 5-year follow-up information were subjected to gene expression profiling and, subsequently, compared to three extensive published OPSCC cohorts to define robust biomarkers for HPV-negative lesions. Validation of Aldo-keto-reductases 1C3 (AKR1C3) by qRT-PCR was carried out on an independent cohort (n = 111) of OPSCC cases. In addition, OPSCC cell lines Fadu and Cal-27 were treated with Cisplatin and/or specific AKR1C3 inhibitors to assess their (combined) therapeutic effects.

Results: Gene set enrichment analysis (GSEA) on the four datasets revealed that the genes down-regulated in HPV-negative samples were mainly involved in immune system, whereas those up-regulated mainly in glutathione derivative biosynthetic and xenobiotic metabolic processes. A panel of 30 robust HPV-associated transcripts was identified, with AKR1C3 as top-overexpressed transcript in HPV-negative samples. AKR1C3 expression in 111 independent OPSCC cases positively correlated with a worse survival, both in the entire cohort and in HPV-positive samples. Pretreatment with a selective AKR1C3 inhibitor potentiated the effect of Cisplatin in OPSCC cells exhibiting higher basal AKR1C3 expression levels.

Conclusions: We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.
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http://dx.doi.org/10.1007/s13402-020-00571-zDOI Listing
April 2021

Running a Radiation Oncology Department at the Time of Coronavirus: An Italian Experience.

Adv Radiat Oncol 2020 Nov 29;5(Suppl 1):3-6. Epub 2020 Oct 29.

Department of Oncology, University of Torino, Torino, Italy.

Starting from Wuhan, China, SARS-CoV-2 has been a catastrophic epidemic involving many countries worldwide. After China, Italy has been heavily affected, and severe measures to limit the spread of the virus have been taken in the last weeks. Radiation oncology departments must guarantee optimal cancer treatments even in such a challenging scenario of an ongoing aggressive epidemic. Adopted preventive measures and recommendations are highlighted for patients, professionals, and clinical operations to minimize the risk of infection while safely treating patients with cancer.
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http://dx.doi.org/10.1016/j.adro.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598890PMC
November 2020

Multicentre clinical radiotherapy audit in rectal cancer: results of the IROCA project.

Radiat Oncol 2020 Aug 27;15(1):208. Epub 2020 Aug 27.

Institut Català d'Oncologia, L'Hospitalet, Avinguda Granvia de l'Hospitalet, 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.

Purpose: To perform a clinical audit to assess adherence to standard clinical practice for the diagnosis, treatment, and follow-up of patients undergoing radiotherapy for rectal cancer treatment in four European countries.

Materials And Methods: Multi-institutional, retrospective cohort study of 221 patients treated for rectal cancer in 2015 at six European cancer centres. Clinical indicators applicable to general radiotherapy processes were evaluated. All data were obtained from electronic medical records.

Results: The audits were performed in the year 2017. We found substantial inter-centre variability in adherence to standard clinical practices: 1) presentation of cases at departmental clinical sessions (range, 0-100%) or multidisciplinary tumour board (50-95%); 2) pretreatment MRI (61.5-100%) and thoracoabdominal CT (15.0-100%). Large inter-centre differences were observed in the mean interval between biopsy and first visit to the radiotherapy department (range, 21.6-58.6 days) and between the first visit and start of treatment (15.1-38.8 days). Treatment interruptions ≥ 1 day occurred in 43.9% (2.5-90%) of cases overall. Treatment compensation was performed in 2.1% of cases. Treatment was completed in the prescribed time in 55.7% of cases.

Conclusions: This multi-institutional clinical audit revealed that most centres adhered to standard clinical practices for most of the radiotherapy processes-related variables assessed. However, the audit revealed marked inter-centre variability for certain quality indicators, particularly inconsistent record keeping. Multiple targets for improvement and/or harmonisation were identified, confirming the value of routine clinical audits to detect potential deviations from standard clinical practice.
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http://dx.doi.org/10.1186/s13014-020-01648-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453535PMC
August 2020

Bladder cancer following renal transplantation: experiences with radical cystectomy and adjuvant radiotherapy.

Minerva Chir 2020 10 6;75(5):378-380. Epub 2020 Aug 6.

Division of Urology, Department of Surgical and Integrated Surgical Sciences, IRCCS San Martino University Hospital, University of Genoa, Genoa, Italy.

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http://dx.doi.org/10.23736/S0026-4733.20.08377-7DOI Listing
October 2020

A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.

Eur J Cancer 2020 08 8;135:130-146. Epub 2020 Jun 8.

Department of Medical Oncology, Oncology and Radiology Institute of Serbia, Belgrade, Serbia.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.
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http://dx.doi.org/10.1016/j.ejca.2020.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834380PMC
August 2020

ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in borderline-resected pancreatic cancer.

Clin Transl Radiat Oncol 2020 Jul 15;23:91-99. Epub 2020 May 15.

Radiotherapy Unit, Department of Translation Medicine, University of Piemonte Orientale, Novara, Italy.

Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise RT modality to intensify the irradiation effect for cancer involving upper abdominal structures and organs, generally delivered with electrons (IOERT). Unresectable, borderline and resectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Encouraging survival rates have been documented in patients treated with preoperative chemoradiation followed by radical surgery and IOERT (>20 months median survival, >35% survival at 3 years). Intensive preoperative treatment, including induction chemotherapy followed by chemoradiation and an IOERT boost, appears to prolong long-term survival within the subset of patients who remain relapse-free for>2 years (>30 months median survival; >40% survival at 3 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted approach in the clinical scenario (maturity and reproducibility of results), and extremely accurate in terms of dose-deposition characteristics and normal tissue sparing. The technique can be adapted to systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend use of IOERT in cases of close surgical margins and residual disease. We hereby report the ESTRO/ACROP recommendations for performing IOERT in borderline-resectable pancreatic cancer.
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http://dx.doi.org/10.1016/j.ctro.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280753PMC
July 2020

Adaptive Strategy for External Beam Radiation Therapy in Prostate Cancer: Management of the Geometrical Uncertainties With Robust Optimization.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e521-e528. Epub 2020 May 25.

Division of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy; Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. Electronic address:

Purpose: We aim to develop and validate a new adaptive method for prostate cancer radiation therapy (RT), using an offline strategy to improve treatment personalization by modeling the internal target volume on individual basis and account for the residual set-up uncertainties by robust optimization.

Methods And Materials: Twenty patients with intermediate-high prostate cancer treated with radical radiation therapy were enrolled. The first step of the offline adaptive RT strategy is the identification of a patient-specific internal target volume based on the kV cone beam computed tomography (kV-CBCT) data sets acquired during the first 5 fractions. The deformable image registration algorithm ANACONDA was used to propagate the clinical target volumes (CTVs) from the reference-planning computed tomography to the CBCTs; these contours were assessed by a radiation oncologist. In the second step, the internal target volume was used to replan the treatment using a min-max robust algorithm based on the worst scenario optimization. The CTV coverage and organs-at-risk sparing achieved with the robust plan (RP) were analyzed and compared with the original standard plan, calculating the dose distributions on the residual CBCTs.

Results: The RP was shown to achieve optimal coverage of the CTV even in the worst scenario, with significantly lower doses to the rectum and bladder. CTV coverage of the RP was statistically better than the standard plan in terms of D99 (P = .008) and D98 (P = .02). Statistically significant mean dose reduction and D2 reduction were noted for the rectum (P < .05) and bladder (P < .009). Moreover, the RP appeared to be less sensitive to bladder and rectal filling.

Conclusions: This adaptive strategy in prostate cancer radiation therapy is feasible and safe; it may be used to adapt the treatment with better target coverage and organs-at-risk sparing than standard planning target volume-based planning.
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http://dx.doi.org/10.1016/j.prro.2020.05.006DOI Listing
May 2020

Skull-base surgery during the COVID-19 pandemic: the Italian Skull Base Society recommendations.

Int Forum Allergy Rhinol 2020 Aug 15;10(8):963-967. Epub 2020 Jun 15.

Division of Maxillo-Facial Surgery, Department of Biomedical, Surgical and Dental Sciences, San Paolo Hospital, University of Milan, Milan, Italy.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment (PPE) is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combating the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was 1 of the earliest and hardest-hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, filtering facepiece 3 (FFP3) and/or powered air purifying respirator (PAPR) devices, goggles, full-face visor, double gloves, water-resistant gowns, and protective caps are mandatory. For negative patients, use of at least an FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS-CoV-2, dura handling should be minimized. It is only through widely-agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic.
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http://dx.doi.org/10.1002/alr.22596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267564PMC
August 2020

Apoptotic and predictive factors by Bax, Caspases 3/9, Bcl-2, p53 and Ki-67 in prostate cancer after 12 Gy single-dose.

Sci Rep 2020 04 27;10(1):7050. Epub 2020 Apr 27.

Department of Translational Medicine, University of Piemonte Orientale (UPO), via Solaroli 17, 28100, Novara, Italy.

Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p < 0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p = 0.0001). At statistical analysis, it was observed that cancer cells with Ki-67 ≥ 8% had a trend toward greater expression of Bax (p = 0.0641). We observed an increase of Bcl-2 expression after IORT in neoplastic areas (p = 0.0041). Biopsy specimens with p53 ≥ 18% and Ki-67 ≥ 8% had worse post-operative staging with extracapsular invasion (p = 0.04 for both parameters) and nodal positivity (p = 0.04 for p53 and p = 0.0001 at pathology for ki-67). No correlation between IORT and Caspases activation was noted. In conclusion, after 12 Gy IORT, Bax was overexpressed in tumor and PIN cells. Pre-operative Ki-67 and p53 definition could be used in future studies to predict patients with worse pathological stage, while Bcl-2 activation after IORT might be a predictive factor for loco-regional failure.
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http://dx.doi.org/10.1038/s41598-020-64062-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184731PMC
April 2020

ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in unresected pancreatic cancer.

Radiother Oncol 2020 07 8;148:57-64. Epub 2020 Apr 8.

Department of Radiation Oncology, University Hospital of Heidelberg, Germany.

Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise sub-component of RT that can intensify the irradiation effect for cancer involving an anatomically well-defined volume, generally delivered with electrons (IOERT). Unresectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Long-term survivors were observed among unresected patients treated with external beam RT and an IOERT boost (OS 6% at 3 years; 3% >5 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted asset in the clinical scenario (maturity and reproducibility of results, albeit of low official level of evidence) and extremely accurate in terms of dose-deposit characteristics and normal tissue sparing. It is a technique that can be integrated with systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend the use of IOERT in cases of close surgical margins and residual disease. We report the ESTRO/ACROP recommendations for performing IOERT in unresected pancreatic cancer.
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http://dx.doi.org/10.1016/j.radonc.2020.03.040DOI Listing
July 2020

Running a Radiation Oncology Department at the Time of Coronavirus: An Italian Experience.

Adv Radiat Oncol 2020 Jul-Aug;5(4):527-530. Epub 2020 Mar 20.

Department of Oncology, University of Torino, Torino, Italy.

Starting from Wuhan, China, SARS-CoV-2 has been a catastrophic epidemic involving many countries worldwide. After China, Italy has been heavily affected, and severe measures to limit the spread of the virus have been taken in the last weeks. Radiation oncology departments must guarantee optimal cancer treatments even in such a challenging scenario of an ongoing aggressive epidemic. Adopted preventive measures and recommendations are highlighted for patients, professionals, and clinical operations to minimize the risk of infection while safely treating patients with cancer.
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http://dx.doi.org/10.1016/j.adro.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102610PMC
March 2020

Postoperative Radiation Therapy in Patients with Extracranial Chondrosarcoma: A Joint Study of the French Sarcoma Group and Rare Cancer Network.

Int J Radiat Oncol Biol Phys 2020 07 11;107(4):726-735. Epub 2020 Apr 11.

Department of Radiation Oncology, Centre Baclesse/ARCHADE-Normandie Université, Caen, France; Laboratoire de Physique Corpusculaire, Caen, France; Unicaen-Normandie Université, Caen, France. Electronic address:

Purpose: Postoperative radiation therapy (poRT) of intracranial/skull base chondrosarcomas (CHSs) is standard treatment. However, consensus is lacking for poRT in extracranial CHS (eCHS) owing to their easier resectability and intrinsic radioresistance. We assessed the practice and efficacy of poRT in eCHS.

Methods And Materials: This multicentric retrospective study of the French Sarcoma Group/Rare Cancer Network included patients with eCHS who were operated on between 1985 and 2015. Inverse propensity score weighting (IPTW) was used to minimize poRT allocation biases.

Results: Of 182 patients, 60.4% had bone and 39.6% had soft-tissue eCHS. eCHS were of conventional (31.9%), myxoid (28.6%; 41 extraskeletal, 11 skeletal), mesenchymal (9.9%), or other subtypes. En-bloc surgery with complete resection was performed in 52.6% and poRT in 36.8% of patients (median dose, 54 Gy). Irradiated patients had unfavorable initial characteristics, with higher grade and incomplete resection. Median follow-up time was 61 months. Five-year incidence of local relapse was 10% with poRT versus 21.6% without (P = .050). Using the IPTW method, poRT reduced the local relapse risk (hazard ratio, 0.27; 95% confidence interval, 0.14-0.52; P < .001). Five-year disease-free survival (DFS) was 71.8% with poRT and 64.2% without (P = .680). Using the IPTW method, poRT improved DFS (hazard ratio, 0.51; 95% confidence interval, 0.30-0.85; P = .010). The benefit of poRT on local relapse and DFS was confirmed after exclusion of the extraskeletal subtype. There was no difference in overall survival. Prognostic factors of poorer DFS in multivariate analysis were deeper location, higher grade, incomplete resection, and no poRT.

Conclusions: poRT should be offered in patients with eCHS and high-grade or incomplete resection, regardless of the histologic subtype.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.041DOI Listing
July 2020

Mixed-beam approach in locally advanced nasopharyngeal carcinoma: IMRT followed by proton therapy boost versus IMRT-only. Evaluation of toxicity and efficacy.

Acta Oncol 2020 May 23;59(5):541-548. Epub 2020 Feb 23.

Scientific Direction, European Institute of Oncology IRCCS, Milan, Italy.

To compare radiation-induced toxicity and dosimetry parameters in patients with locally advanced nasopharyngeal cancer (LANPC) treated with a mixed-beam (MB) approach (IMRT followed by proton therapy boost) with an historic cohort of patients treated with a full course of IMRT-only. Twenty-seven patients with LANPC treated with the MB approach were compared to a similar cohort of 17 patients treated with IMRT-only. The MB approach consisted in a first phase of IMRT up to 54-60 Gy followed by a second phase delivered with a proton therapy boost up to 70-74 Gy (RBE). The total dose for patients treated with IMRT-only was 69.96 Gy. Induction chemotherapy was administrated to 59 and 88% and concurrent chemoradiotherapy to 88 and 100% of the MB and IMRT-only patients, respectively. The worst toxicity occurring during the entire course of treatment (acute toxicity) and early-late toxicity were registered according to the Common Terminology Criteria Adverse Events V4.03. The two cohorts were comparable. Patients treated with MB received a significantly higher median total dose to target volumes ( = .02). Acute grade 3 mucositis was found in 11 and 76% ( = .0002) of patients treated with MB and IMRT-only approach, respectively, while grade 2 xerostomia was found in 7 and 35% ( = .02) of patients treated with MB and IMRT-only, respectively. There was no statistical difference in late toxicity. Local progression-free survival (PFS) and progression-free survival curves were similar between the two cohorts of patients ( = .17 and  = .40, respectively). Local control rate was 96% and 81% for patients treated with MB approach and IMRT-only, respectively. Sequential MB approach for LANPC patients provides a significantly lower acute toxicity profile compared to full course of IMRT. There were no differences in early-late morbidities and disease-related outcomes (censored at two-years) but a longer follow-up is required to achieve conclusive results.
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http://dx.doi.org/10.1080/0284186X.2020.1730001DOI Listing
May 2020

Radiotherapy in the treatment of extracranial hemangiopericytoma/solitary fibrous tumor: Study from the Rare Cancer Network.

Radiother Oncol 2020 03 2;144:114-120. Epub 2019 Dec 2.

Dept. Of Radiation Oncology, Centre A. Lacassagne, Nice, France; Dept. of Radiation Oncology, Centre F. Baclesse, Caen, France.

Background And Purpose: The role of radiotherapy (RT) in the treatment of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) is still under debate. We aimed at investigating whether radiotherapy can improve the results in patients operated for extracranial HPC/SFT.

Materials And Methods: Data from patients with HPC/SFT, treated from 1982 to 2012, were retrospectively reviewed within the Rare Cancer Network framework. Actuarial local control (LC), disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) were calculated with Kaplan-Meyer method. Patient and tumor parameters were analyzed by univariate and multivariate analysis.

Results: Of 114 HPC/SFT, 58 (50.9%) occurred in the extremities/superficial trunk and 56 (49.1%) in intra-thoracic/retroperitoneum. Seventy-eight patients (68.4%) underwent surgery only (Sx), and 36 (31.6%) Sx and RT (Sx + RT). Median RT dose was 60 Gy (range 45-68.4 Gy) in 1.6-2.2 Gy fractions. In the extremities/superficial trunk group of patients, actuarial 5-year LC rates were 50.4% after Sx and 91.6% after Sx + RT (p < 0.0001) for LC, and 50.4% after Sx and 83.1% after Sx + RT (p = 0.008) for DFS. In the intra-thoracic/retroperitoneum group of patients, actuarial 5-year rates were 89.3% after Sx and 77.8% after Sx + RT (p = 0.99) for LC, and 73.8% after Sx and 77.8% after Sx + RT (p = 0.93) for DFS. At multivariate analysis, the addition of RT resulted in better LC and DFS in the whole series. The advantage was confirmed for LC in the group of patients affected by extremity/superficial trunk tumors.

Conclusion: Addition of RT to Sx could improve the prognosis, in terms of LC and DFS, essentially in patients with extremities/superficial trunk tumor locations.
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http://dx.doi.org/10.1016/j.radonc.2019.11.011DOI Listing
March 2020

Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis.

PLoS One 2019 22;14(11):e0225685. Epub 2019 Nov 22.

Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy.

The relationship between the ataxia-telangiectasia mutated (ATM) rs1801516 gene polymorphism and risk of radiation-induced late skin side effects remains a highly debated issue. In the present study, we assessed the role of ATM rs1801516 as risk factor for radiation-induced fibrosis and telangiectasia, using the LENT-SOMA scoring scale in 285 breast cancer patients who received radiotherapy after breast conserving surgery. A systematic review with meta-analysis and trial sequential analysis (TSA) was then conducted to assess reliability of the accumulated evidence in breast cancer patients. In our cohort study, no association was found between ATM rs1801516 and grade ≥ 2 telangiectasia (GA+AA vs GG, HRadjusted: 0.699; 95%CI: 0.273-1.792, P = 0.459) or grade ≥ 2 fibrosis (GA+AA vs GG, HRadjusted: 1.175; 95%CI: 0.641-2.154, P = 0.604). Twelve independent cohorts of breast cancer patients were identified through the systematic review, of which 11 and 9 cohorts focused respectively on the association with radiation-induced fibrosis and radiation-induced telangiectasia. Pooled analyses of 10 (n = 2928 patients) and 12 (n = 2783) cohorts revealed, respectively, no association of ATM rs1801516 with radiation-induced telangiectasia (OR: 1.14; 95%CI: 0.88-1.48, P = 0.316) and a significant correlation with radiation-induced fibrosis (OR: 1.23; 95%CI: 1.00-1.51, P = 0.049), which however did not remain significant after TSA adjustment (TSA-adjusted 95%CI: 0.85-1.78). These results do not support an impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer, nevertheless further large studies are still required for conclusive evidences.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225685PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874351PMC
March 2020

Second breast-conserving therapy with interstitial brachytherapy (APBI) as a salvage treatment in ipsilateral breast tumor recurrence: a retrospective study of 40 patients.

J Contemp Brachytherapy 2019 Apr 29;11(2):101-107. Epub 2019 Apr 29.

Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.

Purpose: Breast-conserving treatment (BCT) have emerged as an alternative to mastectomy in patients with ipsilateral breast tumor recurrence (IBTR). We evaluated survival outcomes and treatment-related toxicity in a series of 40 patients with IBTR, who underwent tumorectomy plus interstitial brachytherapy (APBI) as a salvage treatment.

Material And Methods: Retrospective analysis included 40 patients diagnosed with IBTR and treated with intraoperative (26 patients) or post-operative (14 patients) multicatheter brachytherapy for APBI at our institution between June 2002 and October 2017. We assessed cosmesis, toxicity, overall survival (OS), and cancer-specific survival (CSS).

Results: Tumorectomy was performed in all cases, including intraoperative tumor margin assessment and sentinel node biopsy. Median age was 65 years (range, 41-92). The total prescribed dose was 32 Gy (8 fractions) in 19 patients and 34 Gy (10 fractions) in 20 patients. One elderly patient (age 92) received a single fraction of 16 Gy. Median follow-up was 61.5 months (range, 6-153). A median of 14 tubes were inserted. Mean treated V was 115 cc. Two patients developed a second relapse at 3 and 5 years after salvage treatment: one patient underwent salvage mastectomy and remains alive 10 years after brachytherapy, and the second one developed both local relapse and bone metastasis. The disease is stable at present. Five-year OS and CSS rates were 85.3% and 97.5%, respectively. Two patients died from cancer-related causes. Acute and late toxicity rates were low; seven patients developed acute infectious mastitis. Late fibrosis > grade 3 and late mastitis were observed in 14 and 6 cases, respectively.

Conclusions: Second BCT with APBI as a salvage treatment in ipsilateral breast recurrence achieves good local disease control, with a satisfactory toxicity profile compared to mastectomy. This approach seems to be safe and effective, although more data from randomized trials are needed.
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http://dx.doi.org/10.5114/jcb.2019.84689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536137PMC
April 2019

Outcomes of music therapy interventions in cancer patients-A review of the literature.

Crit Rev Oncol Hematol 2019 Jun 5;138:241-254. Epub 2019 Apr 5.

Psychiatry Institute, Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy; Psychiatry Ward, Azienda Ospedaliera Universitaria Maggiore della Carità, Corso Mazzini 18, Novara, Via Solaroli 17, Italy.

Background: Effectiveness of music-based interventions (MI) on cancer patients' anxiety, depression, pain and quality of life (QoL) is a current research theme. MI are highly variable, making it challenging to compare studies.

Objective And Methods: To summarize the evidence on MI in cancer patients, 40 studies were reviewed following the PRISMA statement. Studies were included if assessing at least one outcome among anxiety, depression, QoL and pain in patients aged ≥ 18, with an active oncological/onco-haematological diagnosis, participating to any kind of Music Therapy (MT), during/after surgery, chemotherapy or radiotherapy.

Results: A positive effect of MI on the outcomes measured was supported. Greater reductions of anxiety and depression were observed in breast cancer patients. MI involving patients admitted to a hospital ward were less effective on QoL.

Conclusion: The increasing evidence about MI effectiveness, tolerability, feasibility and appreciation, supports the need of MI implementation in Oncology, Radiotherapy and Surgery wards, and promotion of knowledge among health operators.
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http://dx.doi.org/10.1016/j.critrevonc.2019.04.004DOI 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

Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study.

Eur J Cancer 2019 04 28;111:69-81. Epub 2019 Feb 28.

Department of Radiation Therapy, Centre Francois Baclesse, Advanced Resource Center for Hadrontherapy in Europe, Caen, France, Unicaen-Normandie Universite. Electronic address:

Introduction: Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.

Methods: This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015.

Results: Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p < 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival.

Conclusion: Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.
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http://dx.doi.org/10.1016/j.ejca.2019.01.004DOI Listing
April 2019

Primary extranodal lymphoma of the glands. Literature review and options for best practice in 2019.

Crit Rev Oncol Hematol 2019 Mar 18;135:8-19. Epub 2019 Jan 18.

APHP, Henri Mondor University Hospital, Department of Radiation Oncology and Henri Mondor Breast Center, University of Paris - Est Créteil (UPEC), INSERM, U955 Eq07, Créteil, France.

Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments.
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http://dx.doi.org/10.1016/j.critrevonc.2019.01.005DOI Listing
March 2019