De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Temporal evolution of quality of life in patients endoscopically treated for sinonasal malignant tumors.

BACKGROUND: The aim of our study is to assess which factors may affect the quality of life (QoL) and its fluctuation over time in adult patients who received endonasal endoscopic oncologic sinus surgery (EOSS) for sinonasal malignancies (SNM) in our center. METHODOLOGY: We analyzed EOSS cases for primary SNM from January 2015 to June 2020. For each patient, we have recorded the age at treatment, gender, smoking habits, use of psychotropic drugs for mood disorders, stage, histotype, type of surgical resection, need for skull-base reconstruction, development of postoperative major complications, and the use of adjuvant intensity-modulated radiotherapy (IMRT). We evaluated the patient's performance status pre-treatment using the ECOG scale. Quality of life was measured using three questionnaires (SNOT-22; ASK-9; EORTC QLQ-C30 version 3). RESULTS: Fifty-five patients were enrolled in our study, of whom thirty-two (58.18%) received adjuvant IMRT. Overall, a significant improvement in all QoL outcomes was observed at eighteen months, while, female sex, higher ECOG scores, advanced stage of disease, and adjuvant IMRT were associated with worse QoL. After 18 months the delta in QoL between women and men worsened (in SNOT-22 and EORTC QLQ-GLOBAL) while if only the most fragile patients according to ECOG are considered, this difference was reduced for both tools. CONCLUSION: Our analysis revealed that IMRT is the element that has the greatest impact on patient's quality of life, in association with the female sex, ECOG >2, and advanced stage of the disease.

Chemo- immunotherapy and radiation in locally advanced head and neck cancer: Where do we stand?

Immunotherapy represents an effective therapeutic option in the management of recurrent/metastatic head and neck squamous cell carcinoma, along with chemotherapy in metastatic disease or radiotherapy/re-irradiation for (locoregionally confined) recurrent disease. On the other hand, concomitant chemo-radiation remains the primary treatment modality in many patients with locally advanced disease. In spite of promising preclinical, it is difficult to clearly establish the role of immunotherapy in the upfront management of locally advanced head and neck squamous cell carcinoma and its integration with the standard of care. In this paper, we discuss/review the main results thus far available and outline some unanswered questions that might help design future clinical trials.

Palliative radiotherapy in older adults with head and neck squamous cell carcinoma: A systematic review.

Locally advanced Head and neck squamous cell carcinoma (SCCHN) represents a common oncologic pathology in older adults (OA). While radiotherapy represents a cornerstone in this context, it is unclear what is the optimal radiation regimen for SCCHN in the palliative setting, especially for OA. This article addresses issues related to palliative radiotherapy (PRT) in this setting with a focus on treatment modalities and toxicity. We also explore the use of quality of life and geriatric assessment in this setting. Medline, Scopus and Embase databases were queried for articles in this setting. We included studies published from January 1, 2000 through June 1, 2020, that were independently evaluated by two authors. Analyzed endpoints were progression free survival (PFS), overall survival (OS) and PRT toxicities. The meta-analysis was performed using Stata v.14. A total of 33 studies were included in this meta-analysis. The pooled median OS is 7.7 months, 2-years OS was worse for higher radiation dose (p = 0.02). The pooled median PFS was 5.4 months, PFS was influenced by EQD2 (p = 0.01), with patients receiving an EQD2 < 40 Gy that presented a poorer outcome. Regarding acute toxicities, most common pooled G3 toxicities were mucositis (7%) and dysphagia (15%). Among late toxicity, most common G3 toxicity was dysphagia in 7% of patients. Radiotherapy should be the most effective palliative treatment in symptomatic SCCHN OA. A tailored approach, guided by geriatric tools, would be indicated to choose the right therapy.

Impact of COVID-19 on patient-doctor interaction in a complex radiation therapy facility.

PURPOSE: In the last months, Italy faced a COVID-19 emergency and implemented preventive measures in order to protect patients and healthcare providers from a disease outbreak. The pandemic control strategies impacted patient experience directly. Questionnaires evaluating patients reported measures (PREMs) may assess critical issues and represent a helpful tool to measure the patient perception of healthcare service. Our aim was to prospectively assess patient satisfaction about doctor-patient interaction in a high-volume radiation therapy and oncology center during the COVID-19 pandemic. METHODS: Cancer patients receiving either systemic and/or radiation treatment underwent a survey. Two validated questionnaires (EORTC QLQ-C30, FACIT-TS-G version 1) and 14 specific questions evaluating patients' perception of COVID-19 measures were administered. RESULTS: One hundred twenty-five patients admitted to our department from 1-30 April 2020 completed the questionnaires. The majority (66.4%) of patients were women and the most common disease was breast cancer (40%). The average Global Health Status (GHS) of EORTC QLQ-C30 was 61.67. Emotional functioning, social, and cognitive domains obtained scores of 75.48, 80.13, and 84.67, respectively. FACIT-TS-G results revealed 120 patients rated the treatments effective and 108 patients thought the side effects were the same as expected or better. Most (89.6%) rated their treatment good, very good, or excellent. Concerning COVID-19-related questions, patients reported overall very good level of information. CONCLUSIONS: Despite the introduction of strict COVID-19 control measures, there was a high level of cancer outpatient satisfaction. The satisfaction levels may influence compliance, continuity of treatments, and patient-doctor communication, impacting the quality of clinical care in the next phases of the pandemic.

Will a tumor pandemic come after the COVID-19 pandemic? Head and Neck cancer perspective.

The COVID-19 pandemic demands a reassessment of head and neck oncology treatment paradigms by posing several challenges for oncology services, with unprecedented pressure on the regional health care system. Since February 2020 this has severely disrupted health-care services, leading to accumulating clinic caseload and substantial delays for operations. The head and neck cancer services have been faced with the difficult task of managing the balance between infection risk to health-care providers and the risk of disease progression from prolonged waiting times. Herein, we share our experience in Firenze (Italy) and propose our action plan on the management of head and neck cancer services via multi-institution collaboration.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Benefit of ablative versus palliative-only radiotherapy in combination with nivolumab in patients affected by metastatic kidney and lung cancer.

PURPOSE: Here, we present the results from a retrospective analysis, with the purpose of evaluating the safety and feasibility of nivolumab and radiotherapy (RT) concomitant association in metastatic kidney and lung cancer patients. MATERIALS AND METHODS: From August 2015 until September 2017, we retrospectively observed 20 patients with metastatic lung and renal cell carcinoma who had been initiated therapy with nivolumab and underwent concomitant RT. RT was administered either as an ablative therapy in the oligometastatic/oligoprogressive setting or as palliative-only treatment for symptomatic patients. Data on progression-free and overall survival (PFS and OS), treatment response and adverse events were collected and reported. Comparison between palliative-only and ablative treatments was performed. RESULTS: PFS and OS were 7 and 12.5 months in the entire population, respectively. Oligoprogressive patients treated with ablative intent, compared to patients undergoing RT with palliative-only intent, had statistically longer PFS (11.5 vs 5.2 months, HR 0.42, CI 0.18-0.98, p 0.03) and OS (17.9 vs 10.31 months, HR 0.41 CI 0.16-1.02, p 0.04). Considering only patients treated with ablative intent, 87.5% showed response to treatment, and complete response was reported in 37.5% of cases. Adverse G2-G3 related to combination treatment were reported as follows: 1 gastrointestinal (nausea), 4 breakthrough pain. CONCLUSIONS: Our data showed significant advantage for oligoprogressive patients treated with RT during nivolumab therapy. No safety alert emerged. These results underline the potential synergistic effects of RT and Immune therapy combination. Our analysis prompts further prospective studies exploring the benefit of integrated treatment strategies.

Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated Patients Affected by Recurrent Prostate Cancer.

AIMS: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. MATERIALS AND METHODS: Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity. CONCLUSION: Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control.

External validation of a rectal cancer outcome prediction model with a cohort of patients treated with preoperative radiochemotherapy and deep regional hyperthermia.

PURPOSE: To validate a nomogram for the prediction of treatment outcomes after preoperative radiochemotherapy and surgery for locally advanced rectal cancer with a cohort of patients treated with additional deep regional hyperthermia. PATIENTS AND METHODS: A total of 86 patients were treated with preoperative radiochemotherapy and deep regional hyperthermia at our institution. For every patient, the 5-year probability for death, distant metastases and local failure based on a previously published nomogram were calculated and patients were divided into three risk groups. RESULTS: Low-lying and clinically lymph node positive tumours were more frequent in the validation cohort. Five-year Kaplan-Meier estimates for overall survival (OS), distant metastases-free survival (DMFS) and local control (LC) were 87.3%, 79.9%, 95.8% (observed) and 75.5%, 71%, 90% (predicted), respectively. Discrimination between low- and high-risk groups was at a significant level for all endpoints. The c-index was 0.81 (OS), 0.67 (DMFS) and 0.92 (LC), respectively. CONCLUSIONS: The nomogram showed reasonable performance when deep regional hyperthermia is incorporated into preoperative therapy. The higher than predicted rates seen for OS and DMFS in particular in the high-risk groups warrant further prospective validation and subsequent investigation of the underlying mechanisms.

Organ preservation in rectal cancer - Challenges and future strategies.

Neoadjuvant radiochemotherapy with subsequent total mesorectal excision is the standard of care for locally advanced rectal cancer. While this multimodal strategy has decreased local recurrences rates below 5%, long-term morbidities are considerable in terms of urinary, sexual or bowel functioning. At the same time approximately 10-20% of patients have no evidence of residual tumour in their surgical specimen. Pioneering studies from Brazil have suggested that surgery can safely be omitted in carefully selected patients with a clinical complete response after radiochemotherapy. Although confirmatory studies showed similar results, challenges in terms of optimizing radiochemotherapy for organ-preservation, appropriate selection of patients for non-operative management and the safety of this approach remain. The present review will summarize the current data on organ-preservation in rectal cancer and discuss the challenges that need to be addressed in future trials.

Gamma Knife Radiosurgery in the management of single and multiple brain metastases.

OBJECTIVES: To evaluate the efficacy and safety of Gamma Knife Radiosurgery (GKRS) in the treatment of single and multiple brain metastases. PATIENTS AND METHODS: From October 2012 to June 2014 106 patients were treated with Radiosurgery (RS) for brain metastases at University of Florence. 77 out of 106 patients had a radiological follow up and their data were analyzed. The target was defined as the enhancing lesion. The prescription dose was defined depending on tumor volume and tumor location. Each patient performed an MRI one month after GKRS for the first three months and every 3 months thereafter. Overall survival was calculated from the day of RS until death. Local recurrence (LR) was defined as radiologic growth of the irradiated lesion, while distant brain recurrence (DBR) was the evidence of brain lesion outside the previous irradiated field. Both the LR and DBR were calculated from the RS till the day of radiological evidence of relapse. The correlations within patient and disease characteristics and the outcomes of survival and disease control were analyzed. RESULTS: Mean follow up was 7.2 ± 4.8 months (range: 2.4-22.8 months). At the time of analysis 21 patients (27.3%) were dead. The overall survival (OS) at 1 year was 74%. On univariate Cox Regression analysis female gender (p=0.043, HR: 0.391, 95% CI: 0.157-0.972) and age >65 years (p=0.003 HR: 4.623, 95% CI: 1.687-12.663) were predictive for survival. On multivariate analysis, age older than 65 years (p=0.005HR: 4.254, 95% CI: 1.544-11.721) was confirmed as associated with worsened overall survival. 19 patients (24.7%) had recurrence in the radiosurgery field. The median time to local failure was 4.8 ± 2.0 months (range: 1.8-9.4 months) from GKRS. On Cox Regression univariate analysis, the only factor associated with higher risk of local failure was a number of treated lesions more than 4 (p=0.015, HR: 3.813, 95% CI: 1.298-11.202), no significant parameters were found at the multivariate analysis. The median time to develop distant brain failure was 6 ± 4.32 months (range: 1.08-21.6 months). Median distant brain control was 74% at 1 year. None of the factors analyzed was statistically significant for the distant brain relapse. The radiosurgery treatment was well tolerated. One patient treated for seven metastases developed seizures 8h after GKRS, he was treated with steroids and anticonvulsants. One patient had radiologic evidence of radionecrosis without any neurological symptoms. CONCLUSIONS: In well-performing patients with stable systemic disease radiosurgery can be performed as an exclusive treatment for brain metastases. Younger patients could have a greater benefit from the RS, on the other hand our finding confirm no correlation between the survival outcome and the number of lesions treated.

Head and neck reconstruction with pedicled flaps in the free flap era.

Nowadays, the transposition of microvascular free flaps is the most popular method for management of head and neck defects. However, not all patients are suitable candidates for free flap reconstruction. In addition, not every defect requires a free flap transfer to achieve good functional results. The aim of this study was to assess whether pedicled flap reconstruction of head and neck defects is inferior to microvascular free flap reconstruction in terms of complications, functionality and prognosis. The records of consecutive patients who underwent free flap or pedicled flap reconstruction after head and neck cancer ablation from 2006 to 2015, from a single surgeon, in the AOUC Hospital, Florence Italy were analysed. A total of 93 patients, the majority with oral cancer (n = 59), were included, of which 64 were pedicled flap reconstructions (69%). The results showed no significant differences in terms of functional outcome, flap necrosis and complications in each type of reconstruction. Multivariate regression analysis of flap necrosis and functional impairments showed no associated factors. Multivariate regression analysis of complicated flap healing showed that only comorbidities remained an explaining factor (p = 0.019). Survival analysis and proportional hazard regression analysis regarding cancer relapse or distant metastasis, showed no significant differences in prognosis of patients concerning both types of reconstruction. In this retrospective, non-randomised study cohort, pedicled flaps were not significantly inferior to free flaps for reconstruction of head and neck defects, considering functionality, complications and prognosis.

CyberKnife stereotactic radiotherapy for isolated recurrence in the prostatic bed.

PURPOSE: To report a clinical experience of stereotactic body radiation therapy (SBRT) for isolated recurrence in the prostatic bed from prostate cancer. MATERIALS AND METHODS: Between November 2011 and November 2013, 16 patients were treated with SBRT for a macroscopic isolated recurrence of prostate cancer in the prostatic bed. All patients were initially treated with radical prostatectomy, and half of them also received radiotherapy. Two schedules of SBRT were used: 30 Gy in 5 fractions in previously irradiated patients, 35 Gy in five fractions in radiotherapy-naïve patients. RESULTS: At a median follow-up of 10 months (range 2-21 months), a significant biochemical response was found in all but one patient. At imaging evaluation, no local progression was noted: 10 patients showed partial response while four stable disease. At the moment of analysis, all 16 patients were alive. Seven of them experienced distant relapse, while nine maintained biochemical control, with no further therapy. Median time to relapse was 9.3 months (range 3-15.2 months). The treatment was well tolerated: One patient experienced G2 acute genitourinary and gastrointestinal toxicity. CONCLUSIONS: Our experience shows that SBRT with CyberKnife for isolated nodal relapse is a safe and well-tolerated treatment.

Cyberknife treatment for low and intermediate risk prostate cancer.

Cyberknife is an emerging treatment for early stage prostate cancer. Between October 2012 and January 2014, 32 patients were treated in our institution. Prescribed dose was 35-36.25 Gy in five fractions. Biochemical response was observed in 22 patients. Four patients experienced G2 acute genitourinary toxicity and in two cases we recorded G3 acute GU toxicity. 5 patients experienced G2 acute proctitis. At last follow up visit, all patients were still alive. 29 remained free of disease at last follow up appointment, while three developed a biochemical recurrence. Our experience confirms the efficacy and safety of Cyberknife for localized prostate cancer.

Stereotactic radiotherapy for isolated nodal recurrence of prostate cancer.

PURPOSE: To report a clinical experience in stereotactic body radiation therapy (SBRT) for isolated nodal metastases from prostate cancer. MATERIALS AND METHODS: Between November 2011 and December 2013, 30 patients (39 lesions) were treated with SBRT, delivered using Cyberknife, for recurrent prostate cancer with isolated nodal metastases. Prescribed doses and schedules of fractionation varied, ranging from 24 Gy in 1 fraction to 36 Gy in 3 fractions. Most commonly used schedules were 30 Gy in 3 fractions and 36 in Gy in 3 fractions on alternating days. Biochemical response, acute and late toxicity were analyzed. RESULTS: At a median follow-up of 12 months (range 2-24.9), a significant reduction of PSA was observed in 24 cases, while PSA was stable in 1 case and raised in 9 cases. At the time of analysis, among the 30 patients treated, two were dead for systemic disease; 12 patients experienced a relapse of disease in other sites. Sixteen patients were still free of disease. In 24 cases, imaging evaluation 3 months after treatment was available. No in-field recurrence was detected. SBRT was well tolerated: One patient experienced G2 acute genitourinary toxicity. Late toxicity was evaluated in patients with more than 6 months of follow-up, and only one complained G1 proctitis. We did not observe any acute or late severe toxicity (≥G3). CONCLUSIONS: Our experience shows that SBRT for isolated nodal relapse from prostate cancer is a safe treatment, with promising results in terms of efficacy.

Impact of sentinel node tumor burden on outcome of invasive breast cancer patients.

BACKGROUND: The tumor status of the axillary lymph nodes is one of the most important prognostic factors in women with early breast cancer (BC). Sentinel lymph node (SLN) biopsy has become the standard staging procedure for patients with invasive BC, largely replacing axillary lymph nodes dissection (ALND). The exact impact on prognosis of SLN tumor burden is still object of controversy. The aim of this study was to correlate the tumor burden in the SLN with the outcome in a large cohort of women. PATIENTS AND METHODS: 1040 consecutive patients with clinical stage I-III invasive BC were prospectively collected on our Institutional BC database from January 2001 to January 2007. Patients were stratified into the following four groups based on the tumor burden of the SLN: macrometastases, tumor deposit ≥2 mm; micrometastases, tumor deposit ≥0.2 mm and <2 mm; isolated tumor cells (ITC), isolated tumor cells or tumor deposit <0.2 mm; negative, in case of patients with no evidence of tumor. RESULTS: At a median follow-up of 8.5 years, the tumor burden of SLN metastases resulted significant predictor of DFS (P < 0.0001) and OS (P = 0.042). Multivariate analysis showed that the tumor burden of SLN metastases and Ki 67 proliferative index maintained the statistical significance. CONCLUSION: Patients with SLN micrometastases or ITC, do not seem to have a worse DFS or OS compared with SLN negative cases. There is a significant decrease in DFS and OS in patients with macrometastatic disease in the SLN.

Hypofractionation in prostate cancer: radiobiological basis and clinical appliance.

External beam radiation therapy with conventional fractionation to a total dose of 76-80 Gy represents the most adopted treatment modality for prostate cancer. Dose escalation in this setting has been demonstrated to improve biochemical control with acceptable toxicity using contemporary radiotherapy techniques. Hypofractionated radiotherapy and stereotactic body radiation therapy have gained an increasing interest in recent years and they have the potential to become the standard of care even if long-term data about their efficacy and safety are not well established. Strong radiobiological basis supports the use of high dose for fraction in prostate cancer, due to the demonstrated exceptionally low values of α / ß . Clinical experiences with hypofractionated and stereotactic radiotherapy (with an adequate biologically equivalent dose) demonstrated good tolerance, a PSA control comparable to conventional fractionation, and the advantage of shorter time period of treatment. This paper reviews the radiobiological findings that have led to the increasing use of hypofractionation in the management of prostate cancer and briefly analyzes the clinical experience in this setting.

Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.

Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing.