Pre-implant magnetic resonance and transrectal ultrasound imaging in high-dose-rate prostate brachytherapy : comparison of prostate volumes, craniocaudal extents, and contours

Purpose: The purpose of this study was to compare the prostate contours drawn by two radiation oncologists and one radiologist on magnetic resonance (MR) and transrectal ultrasound (TRUS) images. TRUS intra- and inter-fraction variability as well as TRUS vs. MR inter-modality and inter-operator variability were studied. Material and methods: Thirty patients affected by localized prostate cancer and treated with interstitial high-dose-rate (HDR) prostate brachytherapy at the National Cancer Institute in Milan were included in this study. Twenty-five patients received an exclusive two-fraction (14 Gy/fraction) treatment, while the other 5 received a single 14 Gy fraction as a boost after external beam radiotherapy. The prostate was contoured on TRUS images acquired before (virtual US) and after (real US) needle implant by two radiation oncologists, whereas on MR prostate was independently contoured by the same radiation oncologists (MR1, MR2) and by a dedicated radiologist (MR3). Absolute differences of prostate volumes ( 06V) and craniocaudal extents ( 06dz) were evaluated. The Dice's coefficient (DC) was calculated to quantify spatial overlap between MR contours. Results: Significant difference was found between Vvirtual and Vlive (p < 0.001) for the first treatment fractions and between VMR1 and VMR2 (p = 0.043). Significant difference between cranio-caudal extents was found between dzvirtual and dzlive (p < 0.033) for the first treatment fractions, between dzvirtual of the first treatment fractions and dzMR1 (p < 0.001) and between dzMR1 and dzMR3 (p < 0.01). Oedema might be responsible for some of the changes in US volumes. Average DC values resulting from the comparison MR1 vs. MR2, MR1 vs. MR3 and MR2 vs. MR3 were 0.95 \ub1 0.04 (range, 0.82-0.99), 0.87 \ub1 0.04 (range, 0.73-0.91) and 0.87 \ub1 0.04 (range, 0.72-0.91), respectively. Conclusions: Our results demonstrate the importance of a multiprofessional approach to TRUS-guided HDR prostate brachytherapy. Specific training in MR and US prostate imaging is recommended for centers that are unfamiliar with HDR prostate brachytherapy

Predictors of Patient-Reported Dysphagia Following IMRT Plus Chemotherapy in Oropharyngeal Cancer

The aim of this cross-sectional study is to evaluate the factors associated with patient-reported dysphagia in patients affected by locally advanced oropharyngeal cancer (OPC) treated with definitive intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CHT), with or without induction CHT. We evaluated 148 OPC patients treated with IMRT and concurrent CHT, without evidence of disease and who had completed their treatment since at least 6 months. At their planned follow-up visit, patients underwent clinical evaluation and completed the M.D. Anderson dysphagia inventory (MDADI) questionnaire. The association between questionnaire composite score (MDADI-CS) and different patients\u2019 and tumor\u2019s characteristics and treatments (covariates) was investigated by univariable and multivariable analyses, the latter including only covariates significant at univariable analysis. With a median time from treatment end of 30 months [range 6\u201374 months, interquartile range (IQR) 16\u201350 months], the median (IQR) MDADI-CS was 72 (63\u201384). The majority of patients (82.4%) had a MDADI-CS 65 60. At multivariable analysis, female gender, human papilloma virus (HPV)-negative status, and moderate and severe clinician-rated xerostomia were significantly associated with lower MDADI-CS. Patient-perceived dysphagia was satisfactory or acceptable in the majority of patients. HPV status and xerostomia were confirmed as important predictive factors for swallowing dysfunction after radiochemotherapy. Data regarding female gender are new and deserve further investigation

RANK expression in EBV positive nasopharyngeal carcinoma metastasis: A ready-to-treat target?

Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumorinfiltrating Tregs. We collected 17 paired FFPE specimen of primary and metachronous metastatic or regionally relapsed EBV related NPC and evaluated RANK expression by immunohistochemistry. All primary tumour specimens resulted not evaluable whereas all metastatic specimens, regardless of sites, showed high RANK IHC expression in the tumor with no staining in normal surrounding tissues. This observation deserves further clarifications and could open the way to trials testing the hypotesis that targeting the RANK/RANKL pathway with denosumab, an already available, clinically approved monoclonal antibody for metastatic bone lesions, might restore proper antitumor immune response in NPC metastatic patients

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer

COVID-19 Outbreak and Cancer Radiotherapy Disruption in Lombardy, Northern Italy

none37nononeJereczek-Fossa B.A.; Palazzi M.F.; Soatti C.P.; Cazzaniga L.F.; Ivaldi G.B.; Pepa M.; Amadori M.; Antognoni P.; Arcangeli S.; Buffoli A.; Beltramo G.; Berlinghieri S.; Bignardi M.; Bracelli S.; Bruschieri L.; Castiglioni S.; Catalano G.; Di Muzio N.; Fallai C.; Fariselli L.; Filippi A.R.; Gramaglia A.; Italia C.; Lombardi F.; Magrini S.M.; Nava S.; Orlandi E.; Pasinetti N.; Sbicego E.L.; Scandolaro L.; Scorsetti M.; Stiglich F.; Tonoli S.; Tortini R.; Valdagni R.; Vavassori V.; Marvaso G.Jereczek-Fossa, B. A.; Palazzi, M. F.; Soatti, C. P.; Cazzaniga, L. F.; Ivaldi, G. B.; Pepa, M.; Amadori, M.; Antognoni, P.; Arcangeli, S.; Buffoli, A.; Beltramo, G.; Berlinghieri, S.; Bignardi, M.; Bracelli, S.; Bruschieri, L.; Castiglioni, S.; Catalano, G.; Di Muzio, N.; Fallai, C.; Fariselli, L.; Filippi, A. R.; Gramaglia, A.; Italia, C.; Lombardi, F.; Magrini, S. M.; Nava, S.; Orlandi, E.; Pasinetti, N.; Sbicego, E. L.; Scandolaro, L.; Scorsetti, M.; Stiglich, F.; Tonoli, S.; Tortini, R.; Valdagni, R.; Vavassori, V.; Marvaso, G

Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas

Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations