[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

Definitive weekly hypofractionated radiotherapy in surgery-ineligible older adults with cutaneous squamous cell carcinoma of the head and neck region.

This study intends to address the impact of weekly hypofractionated radiation therapy with curative intent for cutaneous squamous cell carcinoma of the head and neck region in the elderly population.

Skin metastases from prostate cancer successfully treated with radiation therapy.

Skin metastases from prostate cancer (PCa) are rare, cause considerable discomfort, and usually indicate advanced disease and a poor prognosis. To date, literature accounts for no more than 88 cases of skin metastasis from PCa, and radiation therapy (RT) is not considered a standard treatment option. Here, we have described a rare case of skin localization of castration-resistant metastatic PCa, which occurred in a 75-year-old male previously treated with RT for PCa, 11 years earlier. The skin lesions, which progressively appeared in different areas of the chest wall, were successfully treated with electron beam RT (900 cGy, for 3 consecutive days). Five months after irradiating skin metastases, the patient showed general fair conditions and no longer developed other skin lesions in the areas already treated or elsewhere. This report describes a scarce case of cutaneous metastases from PCa, underlying the crucial role of RT as a definitive palliative treatment that should be used to limit systemic chemotherapy-related toxicity.

Surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region gain clinical benefit from definitive weekly hypofractionated radiotherapy.

BACKGROUND: To evaluate the role of definitive weekly hypofractionated radiotherapy (RT) for the treatment of surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region (cHNSCC). METHODS: Eligible elderly patients (aged ≥75 years) with cHNSCC were included. Patients received definitive weekly hypofractionated RT, using megavoltage electrons, to a total dose of 56-64 Gy (8 Gy per fraction). Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), pain response, tolerability, and safety. RESULTS: A total of 19 patients with 27 lesions were included and treated with definitive weekly hypofractionated RT. All patients received the prescribed total dose. ORR was 92.6%, including 70.4% of lesions with a CR and 22.2% with a PR. Median DOR was 12 months. No severe toxicity occurred. CONCLUSIONS: Our study confirmed the satisfying efficacy and acceptable toxicity of definitive weekly hypofractionated RT for cHNSCC in elderly patients. Our results establish weekly hypofractionated scheduleas a promising treatment option for elderly patients with cHNSCC.

The management of oligometastatic disease in colorectal cancer: Present strategies and future perspectives.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.

Clinical Outcomes and Toxicity of CT-guided High Dose-rate Brachytherapy in Women With Locally-advanced Cervical Cancer.

BACKGROUND/AIM: To evaluate the outcome and toxicities in patients with locally advanced cervical cancer (LACC) treated with radiochemotherapy and intracavitary brachytherapy. PATIENTS AND METHODS: This study included 67 patients with LACC treated between 2010 and 2018. The most represented stage was FIGO IIB. The patients were treated with external beam radiotherapy (EBRT) to the pelvis and boost to the cervix and parametrials. Concomitant chemotherapy (CHT) with cisplatin (CDDP) 40 mg/mq was planned. Subsequently, the patients underwent CT-based endouterine brachytherapy (BT). The response was evaluated at 3 months with PET-CT and/or pelvic magnetic resonance imaging (MRI). Since then, the patients have been followed with clinical instrumental controls every 4 months for the first 2 years and every 6 months for the following 3 years. Local response was assessed with pelvic MRI and/or PET-CT scan at the end of intracavitary BT) according to RECIST 1.1 criteria. RESULTS: The median duration of treatment was 55 days (range=40-73 days). The prescription dose to the planning target volume (PTV) was delivered in 25 to 30 (median 28) daily fractions. The EBRT median dose to the pelvis and gross tumor volume were 50.4 Gy (range=45-56.25) and 61.6 Gy (range=45-70.4), respectively. The 1-year, 2-year, 3-year, and 5-year overall survival rates were 92.44%, 80.81%, 78.84%, and 76.45% respectively. The actuarial 1-year, 2-year, 3-year, and 5-year disease-free survival rates were 89.5%, 83.6%, 81%, and 78.2% respectively. CONCLUSION: This study analyzed acute and chronic toxicity, survival, and local control in cervical cancer patients treated with IMRT followed by CT-planned high dose rate-brachytherapy. Patients demonstrated satisfactory outcomes and incidence of acute and late toxicities.

Focused Ultrasound and External Beam Radiation Therapy for Painful Bone Metastases: A Phase II Clinical Trial.

Background Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT. The primary end point was the overall response rate at 1-month following treatment, assessed via the numeric rating scale (NRS) for pain (0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"). Secondary end points were improvements at 12-month follow-up in NRS and quality of life (QoL) measures, including the Brief Pain Inventory (BPI), QoL-Questionnaire Cancer-15 Palliative Care (QLQ-C15-PAL), and QoL-Questionnaire Bone Metastases-22 (QLQ-BM22) and analysis of adverse events. Statistical analyses, including linear regression, χ2 test, and Student t test followed the per-protocol principle. Results Among 198 participants, 100 underwent MRI-guided focused ultrasound (mean age, 63 years ± 13 [SD]; 51 women), and 98 underwent EBRT (mean age, 65 years ± 14; 52 women). The overall response rates at 1-month follow-up were 91% (91 of 100) and 67% (66 of 98), respectively, in the focused ultrasound and EBRT arms (P < .001), and complete response rates were 43% (43 of 100) and 16% (16 of 98) (P < .001). The mean baseline NRS score was 7.0 ± 2.1 for focused ultrasound and 6.6 ± 2.4 for EBRT (P = .16); at 1-month follow-up, they were reduced to 3.2 ± 0.3 and 5.1 ± 0.3 (P < .001), respectively. QLQ-C15-PAL for physical function (P = .002), appetite (P < .001), nausea and vomiting (P < .001), dyspnea (P < .001), and QoL (P < .001) scores were lower in the focused ultrasound group. The overall adverse event rates were 15% (15 of 100) after focused ultrasound and 24% (24 of 98) after EBRT. Conclusion MRI-guided focused ultrasound surgery and external beam radiation therapy showed similar improvements in pain palliation and quality of life, with low adverse event rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kelekis in this issue.

High-resolution anoscopy predictive modeling of anal canal cancer response after definitive chemoradiotherapy in COVID19 era.

PURPOSE: To develop a predictive index model, integrating both clinical and high-resolution anoscopy (HRA) features to further personalize the decision making process in anal canal carcinoma in COVID19 era. METHODS AND MATERIALS: We assess HRA parameters after definitive chemoradiotherapy in patients with anal canal malignant lesions. RESULTS: HRA features could be important to assess the effect of CRT and a risk stratification system should be introduced in clinical practice to better allocate therapeutic interventions. CONCLUSION: To our knowledge this is the first proposal for HRA findings in anal canal cancer after definitive CRT. We believe that a risk score can be useful to estimate the risk of treatment failure (in term of persistence disease and/or recurrence) and its clinical relevance should not to be underestimated.

Predictive role of diffusion-weighted MRI in the assessment of response to total neoadjuvant therapy in locally advanced rectal cancer.

OBJECTIVE: To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). METHODS: In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis. RESULTS: A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%. CONCLUSIONS: ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy. KEY POINTS: • ADC values of pre-TNT MRI examinations of patients with LARC were significantly associated with a pathological complete response (pCR) and with post-treatment regression of TNM staging. • An ADC value of 1.042 ×10-3 mm2/s was found to be the optimal cutoff value for discriminating between pCR and non-pCR patients, with a sensitivity of 75% and specificity of 70%. • DW-MRI proved to have a potential predictive role in the assessment of response to therapy in patients with LARC, throughout the analysis of ADC map values.

Simultaneously Integrated Boost Affects Survival in Locally Advanced p16-Negative Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Intensity modulated radiotherapy (IMRT) is the standard of care for oropharyngeal cancer management. IMRT can be applied using either the sequential boost or simultaneous integrated boost (SIB-IMRT) techniques. The purpose of the study was to assess the efficacy of sequential boost technique or SIB-IMRT) in locally advanced p16-negative oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Baseline characteristics and treatment outcomes were compared between patients with locally advanced p16-negative oropharyngeal squamous cell carcinoma, who received sequential RT (n=40) and those who received SIB-IMRT (n=38). RESULTS: In total, 78 patients with locally advanced p16-negative oropharyngeal cancer were identified. Mean age was 63 years. Patients treated with SIB-IMRT had better 5-year overall survival (OS; 78.7% vs. 52.5%, p=0.023) and 5-year disease-free survival (DFS; 87.4% versus 63.5%, p=0.046) compared to sequential group. There was no difference of total severe acute and late toxicity (grade ≥3) incidences. Patients treated with SIB technique had higher rates of mild to moderate late xerostomia (73.7% vs. 52.5%), dysgeusia (63.2% vs. 20%), and dysphagia (44.7% vs. 17.5%). CONCLUSION: Compared to sequential technique, SIB-IMRT improved both OS and DFS, but higher mild to moderate late toxicity was observed. As long as RT dose constraints to surrounding normal organs can be maintained, SIB technique should be the technique of choice for locally advanced p16-negative oropharyngeal squamous cell carcinoma treatment.

Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile.

INTRODUCTION: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy. METHODS: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules. RESULTS: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant (p-value ≤ 0.05) correlation with alive status was evidenced for sE-selectin at T1. CONCLUSIONS: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy.

Safety and efficacy of combining afatinib and whole-brain radiation therapy in treating brain metastases from EGFR-mutated NSCLC: a case report and literature review.

Combining EGFR-tyrosine kinase inhibitors (TKIs) to whole brain radiation therapy (WBRT) has been shown to be more effective than EGFR-TKIs or WBRT alone in treating brain metastases (BMs) from EGFR-mutated Non Small-Cell Lung Cancer (NSCLC). However, despite the combination results well tolerated, EGFR-TKIs are often discontinued before WBRT, to reduce the risk of possible side effects, potentially resulting in reduced treatment efficacy and possible progression of intra- and extra-cranial disease. Afatinib, an irreversible inhibitor of EGFR-TK, has been shown to radiosensitize NSCLC in pre-clinical models and, compared to the other EGFR-TKIs, more efficiently penetrates the blood-brain barrier. However, nowadays, only two case reports describe the therapeutic efficiency and safety of combining afatinib with WBRT. Herein, we report on a 58-year-old woman patient with symptomatic BMs from NSLCL, treated with afatinib and concomitant WBRT, 30 Gy in 10 fractions. Treatment induced a remarkable and persistent radiological regression of BMs and the disappearance of neurological symptoms. However, the patient experienced severe skin toxicity of G3, corresponding to the irradiation area. Toxicity was successfully treated pharmacologically, and the patient did not experience any BMs-related symptoms for the next 10 months. She died of COVID-19-related respiratory failure. The association of afatinib with WBRT appears to be a successful strategy in the control of BMs from EGFR-mutated NSCLC. However, it should be considered that the combination could be responsible for serious dermatological toxicity.

Survival Analysis Using the Covid-death Mean-imputation (CoDMI) Algorithm: A First Clinical Application in Radiation Oncology.

BACKGROUND/AIM: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection. PATIENTS AND METHODS: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an "incomplete data" and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model. RESULTS: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up. CONCLUSION: The CoDMI algorithm leads to "unbiased" probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naïve application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi.

Relationship between Salivary Amylase and Xerostomia in Intensity-Modulated Radiation Therapy for Head and Neck Cancer: A Prospective Pilot Study.

PURPOSE: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices. RESULTS: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia. CONCLUSION: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

Synchronous Anal Canal Cancer and Cervical Cancer: Report of a Case and Management Implication.

BACKGROUND: This is the case report of a synchronous anal canal cancer and cervical cancer in a patient who underwent definitive chemoradiotherapy (CRT) and radical surgery for anal canal and cervical carcinoma, respectively. CASE REPORT: A 55-year-old woman was diagnosed with cT4a cN1 Mx anal canal squamous cell carcinoma and stage IA2 cervical squamous cell carcinoma, based on biopsy and imaging. Definitive CRT consisted of radiotherapy (total dose of 59.4 Gy) and concomitant mitomycin (10 mg/m2) and 5-fluorouracil (750 mg/m2/5 daily continuous infusion) during the first and last week of radiation. The patient exhibited a complete clinical and radiological response. A radical hysterectomy with pelvic lymphadenectomy was then performed. At the last follow-up (30 months), the patient is still disease-free without any treatment-associated complications. CONCLUSION: There is limited information in the literature regarding treatment strategy and outcome of patients with synchronous anal canal and cervical cancer. A two-step treatment, including CRT and radical hysterectomy, is likely to be accepted as valid option.

Dental Implant Failure Risk in Post Oncological Patients, a Retrospective Study and Sapienza Head and Neck Unit Decisional Protocol- 7 Years of Follow-Up.

(1) Background: Patients with head and neck cancer are treated by ablative surgery, radiotherapy, chemotherapy, or a combination of these. The side effects of cancer therapies can compromise conventional prosthesis rehabilitation; therefore, dental implants can result in a more effective solution. The aim of the study is to explain how to rehabilitate a patient that underwent head and neck cancer therapy. (2) Methods: This retrospective study conducted from 2015 to 2021 included 223 postoncological patients, aged between 32 and 80 years old. Eighteen patients did not proceed with any treatment, and two died. Therefore, 203 patients have been analyzed and rehabilitated following our decisional protocol, with a mean period of follow-up of 4 years. The implant placement was considered successful when a mean bone loss of 1.6 mm for the first year and a mean of 0.13 mm in subsequent years occurred (3) Results: A total of 161 patients were rehabilitated with a conventional prosthesis, 42 patients (F:M ratio 19:23) with an implant-supported prosthesis and a total of 200 implants were placed; 9 implants were lost (4.5% of 200 implants). Conclusions: The results confirmed that by following our protocol it is possible to obtain an acceptable rate of implant survival, considering the delicacy and complexity of post-oncological patients.

Performance of Machine Learning and Texture Analysis for Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer with 3T MRI.

Background: To evaluate the diagnostic performance of a Machine Learning (ML) algorithm based on Texture Analysis (TA) parameters in the prediction of Pathological Complete Response (pCR) to Neoadjuvant Chemoradiotherapy (nChRT) in Locally Advanced Rectal Cancer (LARC) patients. Methods: LARC patients were prospectively enrolled to undergo pre- and post-nChRT 3T MRI for initial loco-regional staging. TA was performed on axial T2-Weighted Images (T2-WI) to extract specific parameters, including skewness, kurtosis, entropy, and mean of positive pixels. For the assessment of TA parameter diagnostic performance, all patients underwent complete surgical resection, which served as a reference standard. ROC curve analysis was carried out to determine the discriminatory accuracy of each quantitative TA parameter to predict pCR. A ML-based decisional tree was implemented combining all TA parameters in order to improve diagnostic accuracy. Results: Forty patients were considered for final study population. Entropy, kurtosis and MPP showed statistically significant differences before and after nChRT in patients with pCR; in particular, when patients with Pathological Partial Response (pPR) and/or Pathological Non-Response (pNR) were considered, entropy and skewness showed significant differences before and after nChRT (all p < 0.05). In terms of absolute value changes, pre- and post-nChRT entropy, and kurtosis showed significant differences (0.31 ± 0.35, in pCR, −0.02 ± 1.28 in pPR/pNR, (p = 0.04); 1.87 ± 2.19, in pCR, −0.06 ± 3.78 in pPR/pNR (p = 0.0005); 107.91 ± 274.40, in pCR, −28.33 ± 202.91 in pPR/pNR, (p = 0.004), respectively). According to ROC curve analysis, pre-treatment kurtosis with an optimal cut-off value of ≤3.29 was defined as the best discriminative parameter, resulting in a sensitivity and specificity in predicting pCR of 81.5% and 61.5%, respectively. Conclusions: TA parameters extracted from T2-WI MRI images could play a key role as imaging biomarkers in the prediction of response to nChRT in LARC patients. ML algorithms can be used to efficiently combine all TA parameters in order to improve diagnostic accuracy.

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting.

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.

Hearing Loss After Cisplatin-based Chemoradiotherapy for Locally Advanced Head and Neck Cancer: A Prospective Single-institution Study.

BACKGROUND/AIM: A single-institution prospective study was conducted to evaluate hearing loss rate after intensity modulated radiotherapy with concomitant cisplatin-based chemotherapy (CRT) for locally advanced head and neck cancer and identify cochlear dosimetric parameters associated with hearing loss risk. PATIENTS AND METHODS: Hearing assessment, patients' characteristics, tumor-related variables, and cochlear quantitative dosimetric factors for adults with locally advanced head and neck cancer treated with CRT were prospectively collected. Each patient repeated audiometry at baseline (pre-CRT), 1 month after CRT, and then every 3 to 6 months. For each cochlea minimum dose (Dmin), mean dose (Dmean), and maximum dose (Dmax) were extracted from treatment plans. Logistic analysis was used for multivariate modeling. The relation between cochlear dosimetric factors and significant hearing loss was also analyzed with receiver operating characteristic (ROC) curves. RESULTS: Between January 2016 and December 2018, 35 patients (70 cochleae) were included. Most patients (n=29; 82.9%) had primary cancer in a low-risk region (oral cavity, oropharynx, larynx). All patients completed the programmed CRT. During follow-up, significant hearing loss was recorded in 13 cases (37.1%). The ROC areas for significant hearing loss in relation to Dmin, Dmean, and Dmax were 0.70, 0.66, and 0.66, respectively. A dose-dependent relationship was noted between cochlear Dmin and significant hearing loss. CONCLUSION: Dmin <14.4 Gy is associated with reduced rates of significant hearing loss after concomitant cisplatin-based CRT in patients with locally advanced head and neck cancer.

A Machine-Learning-Based Bibliometric Analysis of the Scientific Literature on Anal Cancer.

Squamous-cell carcinoma of the anus (ASCC) is a rare disease. Barriers have been encountered to conduct clinical and translational research in this setting. Despite this, ASCC has been a prime example of collaboration amongst researchers. We performed a bibliometric analysis of ASCC-related literature of the last 20 years, exploring common patterns in research, tracking collaboration and identifying gaps. The electronic Scopus database was searched using the keywords "anal cancer", to include manuscripts published in English, between 2000 and 2020. Data analysis was performed using R-Studio 0.98.1091 software. A machine-learning bibliometric method was applied. The bibliometrix R package was used. A total of 2322 scientific documents was found. The average annual growth rate in publication was around 40% during 2000-2020. The five most productive countries were United States of America (USA), United Kingdom (UK), France, Italy and Australia. The USA and UK had the greatest link strength of international collaboration (22.6% and 19.0%). Two main clusters of keywords for published research were identified: (a) prevention and screening and (b) overall management. Emerging topics included imaging, biomarkers and patient-reported outcomes. Further efforts are required to increase collaboration and funding to sustain future research in the setting of ASCC.