Post-operative intensity-modulated vs 3D conformal radiotherapy after conservative surgery for laryngeal tumours of the supraglottic region: a dosimetric analysis on 20 patients.

Objective: To perform a dosimetric comparison between intensity modulated radiotherapy (IMRT) and 3D conformal radiotherapy in patients with locally advanced (stage III and IV) tumours of the supraglottic region treated with conservative surgery and post-operative radiotherapy. Methods: An in-silico plan using a 3D conformal shrinking field technique was retrospectively produced for 20 patients and compared with actually delivered IMRT plans. Eighteen structures (arytenoids, constrictor muscles, base of tongue, floor of mouth, pharyngeal axis, oral cavity, submandibular glands and muscles of the swallowing functional units [SFU]) were considered. Results: IMRT allowed a reduction of maximum and mean doses to 9 and 14 structures, respectively (p < .05). Conclusions: IMRT achieved a reduction of unnecessary dose to the remnant larynx and the majority of surrounding SFUs. Further prospective analyses and correlations with functional clinical outcomes are required to confirm these dosimetric findings.

Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer-Evidence from a 17-Year Follow-Up Study.

BACKGROUND AND AIM: The involvement of cholesterol in cancer development remains a topic of debate, and its association with breast cancer has yet to be consistently demonstrated. Considering that circulating cholesterol levels depend on several concomitant processes, we tested the liability of plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key regulators of cholesterol levels, as a prognostic biomarker in the context of breast neoplastic events. METHODS: Within a prospective randomized breast cancer prevention trial we measured baseline plasma levels of PCSK9. A total of 235 at-risk premenopausal women were randomized and followed up for 17 years. Participants enrolled in this placebo-controlled, phase II, double-blind trial were randomly assigned to receive either tamoxifen 5 mg/d or fenretinide 200 mg/d, both agents, or placebo for 2 years. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models, adjusted for randomization strata (5-year Gail risk ≥ 1.3% vs. intraepithelial neoplasia or small invasive breast cancer of favorable prognosis), age, and treatment allocation. PCSK9 associations with biomarkers linked to breast cancer risk were assessed on blood samples collected at baseline. RESULTS: The plasmatic PCSK9 median and interquartile range were 207 ng/mL and 170-252 ng/mL, respectively. Over a median follow-up period of 17 years and 89 breast neoplastic events, disease-free survival curves showed a hazard ratio of 1.002 (95% CI: 0.999-1.005, p = 0.22) for women with PCSK9 plasma levels ≥ 207 ng/mL compared to women with levels below 207 ng/mL. No differences between randomization strata were observed. We found a negative correlation between PCSK9 and estradiol (r = -0.305), maintained even after partial adjustment for BMI and age (r = -0.287). Cholesterol (r = 0.266), LDL-C (r = 0.207), non-HDL-C (r = 0.246), remnant cholesterol (r = 0.233), and triglycerides (r = 0.233) also correlated with PCSK9. CONCLUSIONS: In premenopausal women at risk of early-stage breast cancer, PCSK9 did not appear to have a role as a prognostic biomarker of breast neoplastic events. Larger studies are warranted investigating patients in different settings.

Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report.

PURPOSE: Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. METHODS: Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. RESULTS: One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. CONCLUSIONS: HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.

Primary malignant phyllodes tumors of the breast: A retrospective analysis from a referral center.

BACKGROUND: The treatment for primary malignant phyllodes tumors of the breast (B-MPT) consists of wide local excision with negative margins (≥1 cm). However, because of their rarity, prognostic factors, type of surgery and adjuvant treatments are still a matter of debate. METHODS: We conducted a single-center retrospective study to describe outcomes and prognostic factors of patients with primary B-MPT, who underwent breast surgery from January 2000 to December 2021. The primary endpoint was the cumulative incidence of any recurrence. Secondary endpoints were the cumulative incidences of distant and local recurrences. RESULTS: 131 patients were included, of whom all received surgery, 5 adjuvant anthracycline-based chemotherapy and 15 radiation therapy. After a median follow-up of 6.4 years, the cumulative incidences at 5-years of any, local and distant recurrences were of 26% (95% Confidence Interval [CI], 4-34%), 16% (95%CI, 10-24%) and 10% (95%CI, 5.3-16%), respectively. Tumor size ≥ 5 cm was associated with higher distant recurrences (p = 0.05); instead, among small tumors (<5 cm), distant recurrences were higher in those with heterologous differentiation and/or multifocal disease (p = 0.06). Type of breast surgery (mastectomy vs. lumpectomy/excision) was not found to be significantly associated with distant (p = 0.32) or local (p = 0.17) recurrence, even after controlling local recurrence incidence for negative pathologic prognostic factors (p = 0.17). CONCLUSIONS: The natural history of B-MPT is burdened by local and distant recurrences. Pathologic prognostic factors (i.e., tumor size, heterologous differentiation and multifocal disease) more than the type of wide breast surgery (mastectomy vs. lumpectomy) seem to represent the most significant prognostic factor for recurrences.

Are sex and gender considered in head and neck cancer clinical studies?

We analyzed the inclusion of sex and/or gender (S/G) in Head and Neck Cancer (HNC) clinical studies, through inspecting ClinicalTrials.gov (AACT) and the mention of Human Papilloma Virus (HPV) on a specific subgroup, namely oral cavity, larynx and oropharynx. Only 5% of HNC studies mention S/G as a planned analytical variable. Proportionally more observational studies treated S/G as an analytical variable than interventional studies (10% vs 5%, P-value ≤ 0.001), 8% of studies that mentioned S/G involved more than 100 subjects while 4% less than 100 (P-value ≤ 0.001). In randomized protocols, S/G was mentioned more in studies with a planned sample of more than 100 patients and including HPV status (P-value < 0.05). Small controlled studies have lower mention of S/G as an analytical variable than uncontrolled studies (4% and 10%, respectively among studies with less than 100 subjects). Significantly greater mention of S/G as an analytical variable is observed in controlled and randomized studies with a sample size greater than 100 subjects. HPV was mentioned in only 18% of oral cavity-larynx-oropharynx studies. Interventional studies do not regularly account for S/G during HNC study design. Thus, although fundamental, in studies concerning HNC the S/G variable is often not considered. In trials published in scientific journals (P-value = 0.01) and in more recent clinical trials (P-value = 0.002), S/G is taken more into account suggesting an increasing awareness on its importance. However, the need to systematically include S/G in study design clearly emerges, to better highlight sex-related differences in disease incidence and prognosis and best imbue science and medicine with the proper biological and cultural differences.

Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit.

AIMS: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. METHODS: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. RESULTS: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52-66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5-7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80-0.84] for OS and 0.77 [CI: 0.75-0.79] for LRPFS. CONCLUSIONS: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.

The role of radiomics in tongue cancer: A new tool for prognosis prediction.

BACKGROUND: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning. METHODS: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index. RESULTS: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively). CONCLUSION: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery.

Prediction of the Malignancy of a Breast Lesion Detected on Breast Ultrasound: Radiomics Applied to Clinical Practice.

The study aimed to evaluate the performance of radiomics features and one ultrasound CAD (computer-aided diagnosis) in the prediction of the malignancy of a breast lesion detected with ultrasound and to develop a nomogram incorporating radiomic score and available information on CAD performance, conventional Breast Imaging Reporting and Data System evaluation (BI-RADS), and clinical information. Data on 365 breast lesions referred for breast US with subsequent histologic analysis between January 2020 and March 2022 were retrospectively collected. Patients were randomly divided into a training group (n = 255) and a validation test group (n = 110). A radiomics score was generated from the US image. The CAD was performed in a subgroup of 209 cases. The radiomics score included seven radiomics features selected with the LASSO logistic regression model. The multivariable logistic model incorporating CAD performance, BI-RADS evaluation, clinical information, and radiomic score as covariates showed promising results in the prediction of the malignancy of breast lesions: Area under the receiver operating characteristic curve, [AUC]: 0.914; 95% Confidence Interval, [CI]: 0.876-0.951. A nomogram was developed based on these results for possible future applications in clinical practice.

Prognostic impact of germline BRCA1/2 pathogenic variants in breast cancer.

PURPOSE: This study investigates the impact of different subtypes of pathogenic BRCA variants on the prognosis and on the survival of breast cancer (BC) patients. METHODS: Associations between BRCA1/2 pathogenic variants (PVs) mutations, clinicopathological features, locoregional tumor reappearance, and survival data were analyzed. The Gray's test was used to test difference of the cumulative incidence of local relapse between missense/splicing and other mutations, taking into of competing events. The multivariate proportional hazard model was used to assess the independent association between type of mutation and local relapse, after adjustment for other prognostic factors and clinicopathological characteristics. RESULTS: Out of 482 patients, 285 presented 98 different BRCA1 PVs and 201 harbored 103 different BRCA2 PVs. Missense mutations were found in 46 BC patients (9.5%), splicing mutations in 42 (8.6%), deletions in 206 (42.4%), insertions in 73 (15%), indel mutations in 6 (1.2%), nonsense mutations in 86 (17.7%), and large rearrangements in 27 (5.6%). Kalbfleisch and Prentice cumulative incidence curves analysis showed a significantly lower locoregional recurrence incidence in the missense/splicing group (Gray-test P-value = 0.011). We found that the risk of local relapse was 58% less likely in women carrying missense/splicing variants than in those with other PV subtypes (HR 95% CI 0.42 [0.21-0.82]; P-value = 0.0108). No significant differences were observed in overall survival (OS) in all groups. CONCLUSIONS: Having been found to be associated with a lower risk of BC reappearance, germline BRCA1/2 PVs of the missense/splicing subtypes can be used as prognostic predictors and are likely to improve BC patients' management.

Women's perceptions and attitudes to the use of AI in breast cancer screening: a survey in a cancer referral centre.

OBJECTIVE: Although breast cancer screening can benefit from Artificial Intelligence (AI), it is still unknown whether, to which extent or under which conditions, the use of AI is going to be accepted by the general population. The aim of our study is to evaluate what the females who are eligible for breast cancer screening know about AI and how they perceive such innovation. METHODS: We used a prospective survey consisting of a 11-multiple-choice questionnaire evaluating statistical associations with Chi-Square-test or Fisher-exact-test. Multinomial-logistic-regression was performed on items with more than two response categories. Odds ratio (OR) with 95% CI were computed to estimate the probability of a specific response according to patient's characteristics. RESULTS: In the 800 analysed questionnaires, 51% of respondents confirmed to have knowledge of AI. Of these, 88% expressed a positive opinion about its use in medicine. Non-Italian respondents were associated with the belief of having a deep awareness about AI more often than Italian respondents (OR = 1.91;95% CI[1.10-3.33]). Higher education level was associated with better opinions on the use of AI in medicine (OR = 4.69;95% CI[1.36-16.12]). According to 94% of respondents, the radiologists should always produce their own report on mammograms, whilst 77% agreed that AI should be used as a second reader. Most respondents (52%) considered that both the software developer and the radiologist should be held accountable for AI errors. CONCLUSIONS: Most of the females undergoing screening in our Institute approve the introduction of AI, although only as a support to radiologist, and not in substitution thereof. Yet, accountability in case of AI errors is still unsolved. advances in knowledge:This survey may be considered as a pilot-study for the development of large-scale studies to understand females's demands and concerns about AI applications in breast cancer screening.

The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis.

BACKGROUND: Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC). METHODS: We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts "nicotinamide", "chemoprevention", and "skin cancer" up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC. RESULTS: Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48-1.37; I2 = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50-1.55; I2 = 63%), and NMSC (RR 0.82, 95% CI 0.61-1.12; I2 = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma. CONCLUSIONS: The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.

Radiomic Features Applied to Contrast Enhancement Spectral Mammography: Possibility to Predict Breast Cancer Molecular Subtypes in a Non-Invasive Manner.

We aimed to investigate the association between the radiomic features of contrast-enhanced spectral mammography (CESM) images and a specific receptor pattern of breast neoplasms. In this single-center retrospective study, we selected patients with neoplastic breast lesions who underwent CESM before a biopsy and surgical assessment between January 2013 and February 2022. Radiomic analysis was performed on regions of interest selected from recombined CESM images. The association between the features and each evaluated endpoint (ER, PR, Ki-67, HER2+, triple negative, G2-G3 expressions) was investigated through univariate logistic regression. Among the significant and highly correlated radiomic features, we selected only the one most associated with the endpoint. From a group of 321 patients, we enrolled 205 malignant breast lesions. The median age at the exam was 50 years (interquartile range (IQR) 45-58). NGLDM_Contrast was the only feature that was positively associated with both ER and PR expression (p-values = 0.01). NGLDM_Coarseness was negatively associated with Ki-67 expression (p-value = 0.02). Five features SHAPE Volume(mL), SHAPE_Volume(vx), GLRLM_RLNU, NGLDM_Busyness and GLZLM_GLNU were all positively and significantly associated with HER2+; however, all of them were highly correlated. Radiomic features of CESM images could be helpful to predict particular molecular subtypes before a biopsy.

The prognostic role of sex and hemoglobin levels in patients with oral tongue squamous cell carcinoma.

Background: Women and men differ genetically, biologically (sex) and by social construct (gender), possibly impacting on prognostic factors in predicting cancer survival. Hemoglobin levels and immune system activation are players acting in this scenario which could play a role in partly determining prognosis between patients of different sex/gender (S/G). Here, we investigate these factors in patients affected by tongue squamous cell carcinoma. Methods: This is an observational retrospective cohort study. We collected tongue cancer patients' clinical data, including hemoglobin levels and neutrophil lymphocyte ratio (NLR). Overall survival (OS) and disease-free survival (DFS) were compared between women and men considering confounding and prognostic factors in multivariate Cox proportional hazard models. Stratified analyses were also conducted by sex and tumor stage. Result: 576 patients, 39.9% women and 60.1% men, were found eligible for the analysis. Men were more often smokers (p<0.001), alcohol consumers (p<0.001), overweight or obese (p<0.001) and undergoing radiotherapy (p=0.002). In multivariate models for stage I-II, men showed half risk of death and relapse compared to women (HR=0.44; 95%CI 0.24-0.81, p=0.009; HR=0.55; 95%CI 0.34-0.87, p=0.01, for OS and DFS respectively). Moreover, low hemoglobin levels appeared to be an independent prognostic factor for women but not for men in terms of both OS and DFS. Specifically, women with low hemoglobin levels showed a worse tumor outcome (HR=2.66; 95%CI 1.50-4.70; HR=2.09; 95%CI 1.24-3.53, for OS and DFS respectively). Low hemoglobin levels appeared to be a poor OS prognostic factor for women at stage I-II (p<0.004) but not for men (p=0.10). Women with advanced stage tumors, NLR>2.37, who did not performed Radiotherapy and with depth of invasion (DOI)> 10 were associated with a significant increase in relapse and death (all p<0.05). Conclusion: In our cohort of patients with oral tongue squamous cell carcinoma, men present better OS and DFS than women with early stages tumors. Low hemoglobin level was an independent prognostic factor for women, especially at early-stage tumors. For advanced stages (III-IV), sex is not a significant factor related to patients' prognosis.

Prognostic Impact of Post-Diagnosis Smoking Cessation among Bladder Cancer Patients: A Systematic Literature Review and Meta-Analysis.

We reviewed the studies examining whether quitting smoking at or around diagnosis favourably affects the prognosis of bladder cancer (BC) patients, who are often active smokers at diagnosis. We found only nine eligible articles published until 31 January 2022, which encompassed around 5500 BC in total, the majority of which were nonmuscle invasive BC (only one paper included muscle-invasive BC). We used random effects meta-analysis to obtain a summary hazard ratio (SHR) and 95% confidence intervals (CI). The median proportion of smokers who quit at or around diagnosis was 29.8% (range 8.4-43.1%). For the overall, BC-specific, and progression-free survival, the studies were limited in number (n = 3) and provided conflicting results. At the same time, quitters did not appear to have a lower risk of recurrence than continued smokers (SHR 0.99, 95% CI 0.61-1.61). In conclusion, while the evidence is currently not sufficient to draw firm conclusions (especially for patients with muscle-invasive BC), physicians should not refrain from educating smoking BC patients about the benefits of smoking cessation and provide the necessary support.

Upfront transoral robotic surgery (TORS) versus intensity-modulated radiation therapy (IMRT) in HPV-positive oropharyngeal cancer: real-world data from a tertiary comprehensive cancer centre.

Objective: This study aims to provide real-world data on oncologic and functional outcomes of the most modern surgical and non-surgical treatments of locally advanced HPV-positive oropharyngeal cancer. Methods: We reviewed data on patients treated for stage III and IV HPV-positive oropharyngeal squamous cell carcinoma with either endoscopic surgery (Transoral Robotic Surgery, TORS; Transoral Laser Microsurgery, TLM - group A) or intensity-modulated radiotherapy (IMRT - group B). The minimum follow-up required was 6 months. Survival outcomes and toxicities of treatments were evaluated. Results: 30 patients in group A and 66 in group B were eligible for the analysis. 28% of patients in group A underwent a unimodal treatment, while 42% needed trimodal treatment. 90% of patients in group B underwent concurrent chemoradiation. We found no statistically significant difference in survival outcomes (group A: overall survival 97%, progression-free survival 83%; group B: OS 98%, PFS 86%) or toxicities between groups. Conclusions: Both transoral surgery and IMRT provide excellent outcomes in HPV-positive oropharyngeal cancer. Because of the good prognosis, treatments need to be refined to reduce toxicities while preserving oncologic soundness.

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

Intensity-Modulated Radiotherapy (IMRT) following Conservative Surgery of the Supraglottic Region: Impact on Functional Outcomes.

The aim of the present study was to investigate the role of intensity-modulated radiotherapy (IMRT) on the toxicity profile of patients treated with conservative surgery (CS) of the supraglottic (SG) region. Data on patients treated with CS and postoperative radiotherapy (PORT)-IMRT were prospectively collected. Results. In total, 20 patients were analyzed. Of these, six patients (35%) required the positioning of a temporary tracheostomy. The functional larynx preservation rate was 95%. Females had a higher risk of both endoscopic intervention and chondronecrosis, while the median age was significantly higher in patients requiring enteral nutrition. The incidence of long-term severe toxicities was lower in patients treated with IMRT than in the historical 3D-CRT cohort. Patients who had received PORT-IMRT achieved a lower rate of permanent laryngeal and swallowing dysfunctions. Overall, results from the comparison with the historical 3D-CRT cohort favor the IMRTs.

The Association between Vitamin D and Gut Microbiota: A Systematic Review of Human Studies.

Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastrointestinal microbiota alterations. A systematic review of studies with human subjects has been conducted up to January 2021. We included publications reporting the association between gut microbiota and VD, including VD supplementation, dietary VD intake and/or level of 25(OH)D. We identified 25 studies: 14 were interventional and 11, observational. VD supplementation was found to be associated with a significant change in microbiome composition, in particular of Firmicutes, Actinobacteria and Bacteroidetes phyla. Furthermore, Firmicutes were found to be correlated with serum VD. Concerning alpha and beta diversity, a high nutritional intake of VD seems to induce a shift in bacterial composition and/or affects the species' richness. Veillonellaceae and Oscillospiraceae families, in the Firmicutes phylum, more frequently decreased with both increasing levels of 25(OH)D and vitamin D supplementation. We found evidence of an association, even though the studies are substantially heterogeneous and have some limitations, resulting sometimes in conflicting results. To further understand the role of VD on the modulation of the gastrointestinal microbiota, future research should be geared toward well-designed animal-based studies or larger randomized controlled trials (RCTs).