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The role of neoadjuvant and adjuvant hormonal or chemotherapy-based treatments before or after radical prostatectomy in localized or locally advanced high-risk prostate cancer (PCa) is currently debatable. European guidelines recommend adjuvant androgen deprivation therapy (ADT) only in pN1 patients after extended pelvic lymph node dissection based on outdated evidence on standard hormonal agents. The introduction of new-generation androgen receptor targeting agents (ARTAs) has revolutionized the treatment of metastatic PCa and might also impact the perioperative management of patients with high-risk localized disease. In the last years, a renewed interest has also arisen in chemotherapy-based neoadjuvant or adjuvant treatments alone or in combination with ADT and/or ARTAs. In the present review, we gathered the current evidence on the oncological outcomes of neoadjuvant and adjuvant systemic treatments in surgically treated patients with localized or locally advanced PCa. Despite mild benefits in terms of pathologic responses or oncological outcomes reported in some studies investigating ADT and/or chemotherapy in this setting of patients, strong evidence to support their use in clinical practice is lacking. Promising data in favor of ARTAs have been gathered from phase II trials and prospective series, but definitive results from phase III trials are awaited to confirm these findings.

Background and purpose: This exploratory prospective observational study investigated the changes in Health-related Quality of Life (HRQoL) in rectal cancer patients (RCPs), from diagnosis to one-year-post-surgery follow-up and explored the role of physical symptoms and psychological determinants on HRQoL at the different time points. Materials and methods: We assessed HRQoL, psychological distress, coping, affectivity, alexithymia and social support in 43 RCPs treated with preoperative (chemo)radiation and surgery, at three different assessment time points: diagnosis (T0), one month after the end of preoperative treatment (T1), one month after resection surgery (T2), and at follow-up (T3). Results: The data showed that HRQoL decreased during active treatments, especially between T1 and T2 (p = 0.005), before increasing again at follow-up (p = 0.002).Baseline intestinal symptoms (p

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT’s impact on patient management. Sixty castration-sensitive high-risk (ISUP 4–5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22–17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Abstract Background Arthrogryposis multiplex congenita is a rare condition that mainly involves the lower limbs, characterized by severe joint deformity and contracture, muscular atrophy, and functional impairment. Its clinical manifestations are heterogenous and may involve the maxillofacial district as well. Case presentation This case report describes a 20-year-old patient with arthrogryposis multiplex congenita with skeletal crossbite, facial asymmetry, reduced mouth opening and absence of lateral mandibular movement on the left side. After clinical evaluation, the following exams were required: postero-anterior cephalometric tracing, head and neck electromyography, computerized axiography, computed tomography scan, and maxillofacial magnetic resonance imaging. Orthognathodontic evaluation indicated skeletal asymmetry, reduced condylar movements on the left side and abnormally low electromyography activity of the masticatory muscles on the left side. Computed tomography and magnetic resonance imaging revealed unilateral left mandibular hypoplasia, hypotrophy, and fatty infiltration of masticatory muscles on the left side, as well as immobility of the left condyle during mouth opening, and hypoplasia of the left articular disk, which was however not displaced. Surgery was not indicated and conservative orthognathodontic treatment with function generating bite was suggested to balance the occlusal plane, as well as stretching exercises. Conclusions A rare case of arthrogryposis multiplex congenita with maxillofacial involvement illustrates that a patient-centred, multidisciplinary approach with accurate diagnosis is required to formulate the best treatment plan. Because of the considerable damage to the masticatory muscles, conservative orthognathodontic therapy may be the best treatment option.

IntroductionProstate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research.MethodsThe TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study’s prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks.ResultsThe cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage.DiscussionThis study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

Radiotherapy (RT) is a mainstay of Breast Cancer (BC) patients therapy. Nonetheless, unintended irradiation of the heart and its substructures can result in cardiac toxicity, jeopardizing long-term survivors’ quality of life (QOL). Advances in RT delivery techniques deeply impacted this clinical scenario. Indeed, given the non-negligible burden of cardiotoxicity, modern cardiac sparing approaches have a pivotal role. Nonetheless, further evidence is eagerly awaited regarding patients’ selection, clinical predictors, biological markers, and particularly heart substructures dose-constraints.

BackgroundThe COVID-19 pandemic has likely affected the most vulnerable groups of patients and those requiring time-critical access to healthcare services, such as patients with cancer. The aim of this study was to use time trend data to assess the impact of COVID-19 on timely diagnosis and treatment of head and neck cancer (HNC) in the Italian Piedmont region.MethodsThis study was based on two different data sources. First, regional hospital discharge register data were used to identify incident HNC in patients ≥18 years old during the period from January 1, 2015, to December 31, 2020. Interrupted time-series analysis was used to model the long-time trends in monthly incident HNC before COVID-19 while accounting for holiday-related seasonal fluctuations in the HNC admissions. Second, in a population of incident HNC patients eligible for recruitment in an ongoing clinical cohort study (HEADSpAcE) that started before the COVID-19 pandemic, we compared the distribution of early-stage and late-stage diagnoses between the pre-COVID-19 and the COVID-19 period.ResultsThere were 4,811 incident HNC admissions in the 5-year period before the COVID-19 outbreak and 832 admissions in 2020, of which 689 occurred after the COVID-19 outbreak in Italy. An initial reduction of 28% in admissions during the first wave of the COVID-19 pandemic (RR 0.72, 95% CI 0.62–0.84) was largely addressed by the end of 2020 (RR 0.96, 95% CI 0.89–1.03) when considering the whole population, although there were some heterogeneities. The gap between observed and expected admissions was particularly evident and had not completely recovered by the end of the year in older (≥75 years) patients (RR: 0.88, 0.76–1.01), patients with a Romano-Charlson comorbidity index below 2 (RR 0.91, 95% CI: 0.84–1.00), and primary surgically treated patients (RR 0.88, 95% CI 0.80–0.97). In the subgroup of patients eligible for the ongoing active recruitment, we observed no evidence of a shift toward a more advanced stage at diagnosis in the periods following the first pandemic wave.ConclusionsThe COVID-19 pandemic has affected differentially the management of certain groups of incident HNC patients, with more pronounced impact on older patients, those treated primarily surgically, and those with less comorbidities. The missed and delayed diagnoses may translate into worser oncological outcomes in these patients.

Prostate-specific-membrane-antigen/positron-emission-tomography (PSMA-PET) can accurately detect disease localizations in prostate cancer (PCa) patients with early biochemical recurrence/persistence (BCR/BCP), allowing for more personalized image-guided treatments in oligometastatic patients with major impact in the case of bone metastases (BM). Therefore, this study aimed to identify predictors of BM at PSMA-PET in early-BCR/BCP hormone-sensitive PCa (HSPC) patients, previously treated with radical intent (radiotherapy or radical prostatectomy ± salvage-radiotherapy (SRT)). A retrospective analysis was performed on 443 68Ga-PSMA-11-PET/CT scans. The cohort median PSA at PET-scan was 0.60 (IQR: 0.38–1.04) ng/mL. PSMA-PET detection rate was 42.0% (186/443), and distant lesions (M1a/b/c) were found in 17.6% (78/443) of cases. BM (M1b) were present in 9.9% (44/443) of cases, with 70.5% (31/44) showing oligometastatic spread (≤3 PSMA-positive lesions). In the multivariate binary logistic regression model (accuracy: 71.2%, Nagelkerke-R2: 13%), T stage ≥ 3a (OR: 2.52; 95% CI: 1.13–5.60; p = 0.024), clinical setting (previous SRT vs. first-time BCR OR: 2.90; 95% CI: 1.32–6.35; p = 0.008), and PSAdt (OR: 0.93; 95% CI: 0.88–0.99; p = 0.026) were proven to be significant predictors of bone metastases, with a 7% risk increment for each single-unit decrement of PSAdt. These predictors could be used to further refine the indication for PSMA-PET in early BCR/BCP HSPC patients, leading to higher detection rates of bone disease and more personalized treatments.

Abstract Background To evaluate clinical outcomes of simultaneous integrated boost (SIB) - intensity modulated radiotherapy (RT) in patients with non metastatic anal cancer compared to those of a set of patients treated with 3-dimensional conformal RT and sequential boost (SeqB). Methods A retrospective cohort of 190 anal cancer patients treated at 3 academic centers with concurrent chemo-RT employing either SIB or SeqB was analysed. The SIB-group consisted of 87 patients, treated with 2 cycles of Mitomycin (MMC) and 5-Fluorouracil (5FU) using SIB-IMRT delivering 42-45Gy/28–30 fractions to the elective pelvic lymph nodes and 50.4-54Gy/28-30fractions to the primary tumor and involved nodes, based on pre-treatment staging. The SeqB group comprised 103 patients, treated with MMC associated to either 5FU or Capecitabine concurrent to RT with 36 Gy/20 fractions to a single volume including gross tumor, clinical nodes and elective nodal volumes and a SeqB to primary tumor and involved nodes of 23.4 Gy/13 fractions. We compared colostomy-free survival (CFS), overall survival (OS) and the cumulative incidence of colostomy for each radiation modality. Cox proportional-hazards model addressed factors influencing OS and CFS. Results Median follow up was 34 (range 9–102) and 31 months (range 2–101) in the SIB and SeqB groups. The 1- and 2-year cumulative incidences of colostomy were 8.2% (95%CI:3.6–15.2) and 15.0% (95%CI:8.1–23.9) in the SIB group and 13.9% (95%CI: 7.8–21.8) and 18.1% (95%CI:10.8–27.0) in the SeqB group. Two-year CFS and OS were 78.1% (95%CI:67.0–85.8) and 87.5% (95%CI:77.3–93.3) in the SIB group and 73.5% (95%CI:62.6–81.7) and 85.4% (95%CI:75.5–91.6) in the SeqB, respectively. A Cox proportional hazards regression model highlighted an adjusted hazard ratio (AdjHR) of 1.18 (95%CI: 0.67–2.09;p = 0.560), although AdjHR for the first 24 months was 0.95 (95%CI: 0.49–1.84;p = 0.877) for the SIB approach. Conclusions SIB-based RT provides similar clinical outcomes compared to SeqB-based in the treatment of patients affected with non metastatic anal cancer.

Objective: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. Materials and methods: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). Results: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58–0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67–0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85–4.78) than without (4.14; SD: ±2.97; range: 2.18–5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08–32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14–48.72). Conclusions: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols. Keywords: Rectal cancer, Neoadjuvant radiotherapy, Interobserver variability, Contouring, Target volume delineation

Abstract Background Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Methods Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9–14.4 Gy/5–8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33–0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53–1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response – HR:5.43;95% CI:2.75–10.7; p