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Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25–40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC.

PurposeDoses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity.MethodA systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: “urethra-steering” SBRT (restriction of hotspots to the urethra) and “urethra dose-reduction” SBRT (dose reduction to urethra below the prescribed dose).ResultsBy limiting the urethra Dmax to 90GyEQD2 (α/β = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years.ConclusionUS-SBRT techniques limiting maximum doses to urethra below a 90GyEQD2 (α/β = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.

The expanding clinical application of CDK4- and CDK6-inhibiting drugs in the managements of breast cancer has raised a great interest in testing these drugs in other neoplasms. The potential of combining these drugs with other therapeutic approaches seems to be an interesting work-ground to explore. Even though a potential integration of CDK4 and CDK6 inhibitors with radiotherapy (RT) has been hypothesized, this kind of approach has not been sufficiently pursued, neither in preclinical nor in clinical studies. Similarly, the most recent discoveries focusing on autophagy, as a possible target pathway able to enhance the antitumor efficacy of CDK4 and CDK6 inhibitors is promising but needs more investigations. The aim of this review is to discuss the recent literature on the field in order to infer a rational combination strategy including cyclin-D1/CDK4-CDK6 inhibitors, RT, and/or other anticancer agents targeting G1-S phase cell cycle transition.

Background: Stereotactic body radiation therapy (SBRT) is the most commonly used metastasis-directed therapy (MDT) for oligometastatic urothelial carcinoma (omUC). Despite efforts in defining this disease entity, open questions remain concerning the role of MDT and the use of biomarkers, imaging, and its combination with systemic therapies. The aim of the present systematic review is to provide an updated overview of the current clinical evidence on SBRT for omUC in terms of survival and local control benefits. We also aim to provide updates on controversial areas and future directions in this emerging field. Methods: With a systematic approach, following PRISMA recommendations, we searched two databases to identify and select articles published up until March 2024 reporting the use of SBRT for omUC with or without concomitant systemic therapies. Prospective randomized or non-randomized studies as well as retrospective studies were included. Results: Eight studies were selected for data extraction and 293 omUC patients treated with SBRT were collectively analyzed. In metachronous omUC patients, SBRT delivered with ablative doses (BED10 ≥ 78 Gy) was associated with a 2-year overall survival (OS) rate of 50.7% (95% CI 35.1–64.4%). The use of sub-ablative SBRT doses (BED10 = 43.2 Gy) in combination with immunotherapy did not demonstrate significant clinical outcome improvement in two prospective studies. The overall tolerance was good, with only one study reporting toxicity of grade 3 in up to 18% of the patients treated with SBRT in combination with immunotherapy. Conclusions: SBRT is an effective and widely available MDT option in omUC, although this is based on a limited number of studies. Despite the attempt to use SBRT as an immune response trigger in combination with immunotherapy, no significant improvement in survival outcomes has been observed. The integration of new systemic agents with MDT will likely define a new scenario for the treatment of omUC. The review protocol was registered in PROSPERO, ID: CRD42024522381.

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefore, carried out in order to correlate the above-mentioned TA parameters with the frequency of pathological responses in the examined patients’ population focusing on the detection of complete pathological response (pCR, with no viable cancer cells: TRG 1) as main statistical endpoint. ROC curves were performed on three different datasets considering that on the 21 patients, only 21% achieved an actual pCR. In our training dataset series, pCR frequency significantly correlated with ADC GLCM-Entropy only, when univariate and binary logistic analysis were performed (AUC for pCR was 0.87). A confirmative binary logistic regression analysis was then repeated in the two remaining validation datasets (AUC for pCR was 0.92 and 0.88, respectively). Overall, these results support the hypothesis that D-TA may have a significant predictive value in detecting the occurrence of pCR in our patient series. If confirmed in prospective and multicenter trials, these results may have a critical role in the selection of patients with locally advanced rectal cancer who may benefit form radical surgery after neoadjuvant chemoradiotherapy.

BackgroundRecent evidence has indicated an increased risk of Barrett’s esophagus (BE) in the long term after sleeve gastrectomy (SG).AimThe aim of the study is to investigate the spectrum of gastroesophageal reflux disease (GERD) symptoms as well as the prevalence of BE, at minimum 5 years after SG in patients who underwent SG in different bariatric centers of two countries: France and Italy.Patients and MethodsFive high volume outpatient centers dedicated to bariatric surgery that routinely perform upper GI endoscopy before any bariatric procedures were invited to participate in the study. From January 2017 to June 2018, each center during scheduled postoperative evaluation after surgery asked a minimum 10 consecutive patients, which had performed SG at least 5 years before and with no evidence of BE preoperatively, to undergo another upper GI endoscopy.ResultsNinety (66 F) consecutive patients were enrolled. The mean follow-up was 78 ± 15 months, and the mean total body weight loss was 25 ± 12%. The prevalence of BE was 18.8% with no significant difference among centers. Weight loss failure was significantly associated with BE (p < 0.01). The prevalence of GERD symptoms, erosive esophagitis, and the usage of PPIs increased from 22%, 10%, and 22% before the SG to 76%, 41%, and 52% at the time of follow-up, respectively (p < 0.05).ConclusionsThis multicenter study show a high rate of BE at least 5 years after SG. Weight loss failure was significantly associated with BE. We suggest to provide systematic endoscopy in these patients to rule out this condition.

BackgroundHiatal hernia (HH) is common in obese patients undergoing bariatric surgery. Preoperative traditional techniques such as upper gastrointestinal endoscopy (UGIE) or barium swallow/esophagram do not always correlate with intraoperative findings. High-resolution manometry (HRM) has shown a higher sensitivity and specificity than traditional techniques in non-obese patients in the HH diagnosis, whereas there is a lack of data in the morbidly obese population. We aimed to prospectively assess the diagnostic accuracy of HRM in HH detection, in comparison with barium swallow and UGIE, assuming intraoperative diagnosis as a standard of reference.MethodsForty-one consecutive morbidly obese patients prospectively recruited from a tertiary-care referral hospital devoted to bariatric and metabolic surgery underwent a preoperative evaluation including standardized GERD questionnaires, barium swallow, UGIE, and HRM. The surgical procedures were performed by a single surgeon who was blinded to the results of other investigations.ResultsHH was intraoperatively diagnosed in 11/41 patients (26.8%). In 10/11 patients, the preoperative HRM showed an esophagogastric junction suggestive of HH. When compared to intraoperative evaluation, the sensitivity of the HRM was 90.9% and the specificity 63.3%, with a positive predictive value of 47.6% and a negative predictive value of 95.0%. HRM showed a higher sensitivity and specificity compared to barium swallow and UGIE.ConclusionsHRM has a high accuracy of HH detection in morbidly obese patients assuming an intraoperative diagnosis as reference standard. It could therefore be a very useful tool in the preoperative work-up of obese patients undergoing bariatric surgery.

BackgroundRevisional bariatric surgery (RBS) constitutes a possible solution for patients who experience an inadequate response following bariatric surgery or significant weight regain following an initial satisfactory response. This paper reports results from the first modified Delphi consensus-building exercise on RBS.MethodsWe created a committee of 22 recognised opinion-makers with a special interest in RBS. The committee invited 70 RBS experts from 27 countries to vote on 39 statements concerning RBS. An agreement amongst ≥ 70.0% experts was regarded as a consensus.ResultsSeventy experts from twenty-seven countries took part. There was a consensus that the decision for RBS should be individualised (100.0%) and multi-disciplinary (92.8%). Experts recommended a preoperative nutritional (95.7%) and psychological evaluation (85.7%), endoscopy (97.1%), and a contrast series (94.3%). Experts agreed that Roux-Y gastric bypass (RYGB) (94.3%), One anastomosis gastric bypass (OAGB) (82.8%), and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) (71.4%) were acceptable RBS options after gastric banding (84.3%). OAGB (84.3%), bilio-pancreatic diversion/duodenal switch (BPD/DS) (81.4%), and SADI-S (88.5%) were agreed as consensus RBS options after sleeve gastrectomy. lengthening of bilio-pancreatic limb was the only consensus RBS option after RYGB (94.3%) and OAGB (72.8%).ConclusionExperts achieved consensus on a number of aspects of RBS. Though expert opinion can only be regarded as low-quality evidence, the findings of this exercise should help improve the outcomes of RBS while we develop robust evidence to inform future practice.

The time-base used by digital storage oscilloscopes allows limited selections of the sample rate, namely constrained to a few integer submultiples of the maximum sample rate. This limitation offers the advantage of simplifying the data transfer from the analog-to-digital converter to the acquisition memory, and of assuring stability performances, expressed in terms of absolute jitter, that are independent of the chosen sample rate. On the counterpart, it prevents an optimal usage of the memory resources of the oscilloscope and compels to post processing operations in several applications. A time-base that allows selecting the sample rate with very fine frequency resolution, in particular as a rational submultiple of the maximum rate, is proposed. The proposal addresses the oscilloscopes with time-interleaved converters, that require a dedicated and multifaceted approach with respect to architectures where a single monolithic converter is in charge of signal digitization. The proposed time-base allows selecting with fine frequency resolution sample rate values up to 200 GHz and beyond, still assuring jitter performances independent of the sample rate selection.

This work presents a comparison of different commercial tapes belonging to the second-generation High-Temperature Superconductors (2G HTS) produced by SuNAM Co., Ltd., SuperOx, and Shanghai Superconductors Technology Co., Ltd. (SST) companies. The aim is to investigate pinning mechanisms responsible for best performances, looking at the anisotropy of the irreversibility field and of the flux pinning energy. The irreversibility line states the upper limit of current-carrying capacity, whereas the flux pinning energy explores the ability of material defects to act as weak collectively or strong single vortex pinning centers. All investigated samples have artificial pinning centers (APCs) included in the superconducting matrix: BHO-doped EuBCO for SST, Y2O3 in YBCO for SuperOx, and Gd2O3 particles trapped in GdBCO for SuNAM. Resistive transition curves were measured in high magnetic fields up to 16 T for magnetic field orientations parallel and perpendicular to the tape surface. We found that the anistropy of SST tape shows an overall independence both on temperature and magnetic field, while the other two samples show a more complex behavior. This leads to the conclusion that properly engineered APC optimization in coated conductors can further reduce anisotropy of superconducting properties.