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(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42–81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

AimA prospective dose escalation trial was developed to evaluate the maximum tolerated dose of stereotactic body radiotherapy (SABRT) to primary breast cancer in stage IV disease. The aim of the present report was to describe safety and outcome of the first dose level cohort of patients.Material and methodsPatients with histologically confirmed diagnosis of invasive breast carcinoma (biological immuno-histochemical profile: luminal and/or HER2 positive) and distant metastatic disease not progressing after 6 months of systemic therapy with a tumor CT or 5FDG-PET detectable were deemed eligible. The starting dose was 40 Gy in 5 fractions (level 1) because this dose proved to be safe in previous dose-escalation trial on adjuvant stereotactic body radiotherapy. The maximum dose level was chosen as 45 Gy in 5 fractions. Dose limiting toxicity was any grade 3 or worse toxicity according to CTCAE v.4. Time-to-event Keyboard (TITE-Keyboard) design (Lin and Yuan, Biostatistics 2019) was used to find the maximum tolerated dose (MTD). MTD was the dose of radiotherapy associated with a ≤ 20% rate pre-specified treatment-related dose-limiting toxicity (DLT).ResultsTo date 10 patients have been treated at the starting dose level. Median age was 80 years (range 50-89). 7 patients had a luminal disease, while 3 patients had an HER2 positive disease. No patient suspended ongoing systemic treatment. No protocol defined DLTs were observed. Grade 2 skin toxicity occurred in 4 patients with diseases located close to or involving the skin. Median follow-up was 13 months and all 10 patients were evaluable for response: 5 achieved a complete response, 3 achieved a partial response and 2 showed a stable disease, all with a clinical benefit (resolution of skin retraction, bleeding and pain). The mean reduction in the sum of the largest diameters of target lesions was of 61.4% (DS=17.0%).ConclusionsSABR to primary breast cancer seems feasible and is associated with symptoms reduction. Continued accrual to this study is needed to confirm the safety and assess the MTD.Clinical trial registrationClinicalTrials.gov, identifier NCT05229575.

Purpose In the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer. Methods and Materials Patients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival. Results Fifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively. Conclusions De-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

Aims To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. Methods From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. Results Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. Conclusions CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

Brain metastases (BMs) are common among patients affected by HER2+ metastatic breast cancer (>30%). The management of BMs is usually multimodal, including surgery, radiotherapy, systemic therapy and palliative care. Standard brain radiotherapy (RT) includes the use of stereotactic radiotherapy (SRT) for limited disease and whole brain radiotherapy (WBRT) for extensive disease. The latter is an effective palliative treatment but has a reduced effect on brain local control and BM overall survival, as it is also associated with severe neurocognitive sequelae. Recent advances both in radiation therapy and systemic treatment may change the paradigm in this subset of patients who can experience long survival notwithstanding BMs. In fact, in recent studies, SRT for multiple BM sites (>4) has shown similar efficacy when compared to irradiation of a limited number of lesions (one to three) without increasing toxicity. These findings, in addition to the introduction of new drugs with recognized intracranial activity, may further limit the use of WBRT in favor of SRT, which should be employed for treatment of both multiple-site BMs and for oligo-progressive brain disease. This review summarizes the supporting literature and highlights the need for optimizing combinations of the available treatments in this setting, with a particular focus on radiation therapy.

Simple Summary Brain metastases (BM) may affect a large portion of metastatic HER2-positive BC patients. Dual human epidermal growth factor receptor 2 (HER2) blockade with Pertuzumab and Trastuzumab (PT) in conjunction with chemotherapy represents the first line therapy of metastatic HER2- positive breast cancer (BC) and shows to prolong time to BM development as the first site of disease progression. When limited brain disease occurs with stable extracranial disease, current guidelines suggest to continue systemic therapies and add local brain treatment. However not data are available on the association between PT and stereotactic brain radiotherapy (SRT). This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and PT in patients with breast cancer BM. Abstract (1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

In March 2020, the World Health Organization (WHO) characterized the outbreak of the coronavirus disease 2019 (COVID-19) as a pandemic. The aim of this study was to evaluate the psychological impact of the COVID-19 pandemic on cancer patients undergoing radiotherapy. Were enrolled 210 patients in treatment and in follow-up who had access to the Radiation Oncology Department of the Campus Bio-Medico University Hospital Foundation between April and May 2020. The sample was subjected to structured interview and validated questionnaires. 37

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases‐free survival (DMFS), progression‐free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut‐offs, An equivalence of stereotactic body radiotherapy (SBRT) and chemoradiation (CRT) has been only suggested in some retrospective studies in pancreatic cancer (PC). This is the first matched case‐control study comparing SBRT and CRT in PC considering several endpoints. An equivalence in terms of overall survival, disease free survival, and metastasis free survival among the two treatments and an advantage of SBRT in terms of local control were recorded. Therefore, SBRT is almost comparable to standard CRT.

Simple Summary Pancreatic cancer remains a disease with a dismal outlook for patients, with high relapse rates after surgery and adjuvant treatments. Thanks to the high conformality achievable with advanced radiotherapy techniques, a more robust definition of clinical target volume (CTV) margins is mandatory. Moreover, a precise CTV definition may affect local control, minimizing radiation-related toxicity and allowing dose escalation. Contrary to two recent studies, RTOG contouring guidelines are not based on a pattern of failure analysis. We provided a local failure risk map in resected pancreatic cancer, validating the results of previous studies. Moreover, according to a new probabilistic approach, we provided new CTV contouring guidelines for the postoperative radiotherapy of pancreatic cancer, modeling targets’ margins on a combination of our validated local failure map (30% of local failures) and RTOG guidelines (70% of local failures). Abstract The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

Objective To evaluate the early toxicity of concurrent use of radiotherapy in association with CDK4/6 inhibitors (palbociclib or ribociclib) in patients with hormone-receptors positive metastatic breast cancer. Material and methods Records of patients with histologically proven metastatic or locally advanced breast cancer treated in our institution were reviewed. Patients who received radiotherapy and concurrent palbociclib or ribociclib were selected. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE V4.0). Results Sixteen consecutive metastatic breast cancer patients with 24 radiotherapy treatments were studied. Thirteen patients (81.3%) received palbociclib, 3 (18.7%) patients received ribociclib concurrently with RT (18 and 5 radiotherapy courses respectively). The majority of patients (68.7%) received palliative radiotherapy to the bones (median dose 30 Gy, range 8–36 Gy). Five patients (31.2%) were treated in oligo-metastatic or oligo-progressive sites of disease with higher doses (median dose = 50 Gy, range 39.6–60 Gy). The most common toxicity observed was hematological toxicity. Neutropenia was common (grade 2 = 12.5%; grade 3 = 25%, grade 4 = 6.3%); 60% of patients experiencing grade ≥ 3 neutropenia had already experienced neutropenia during previous cycles of palbociclib. One patient (6.3%) completed the RT course earlier (48 Gy of 50 Gy prescribed) and another patient (6.3%) suspended RT for 2 days. Conclusion concomitant treatment of CDK4/6 and radiotherapy seems well tolerated; high grade hematological toxicity is common, but did not change treatment course in the majority of patients. Previous toxicity should be carefully evaluated as it usually reoccurs.

Aim Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer. Methods A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume. Results FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer. Conclusion Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach.

Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy.

Purpose Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people. Design PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab". Studies performing RT and TT/IT in people aged >65-years were evaluated focusing on safety, toxicity and efficacy. Studies eligible for inclusion were: case reports, retrospective/prospective studies in which RT and new drugs were used concomitantly or sequentially, focusing on elderly sub-group. Results The systematic search identified 626 records. After exclusion of duplicates, full-text review, cross-referencing and paper that did not respect the inclusion criteria, 81 studies were included in this review. In elderly patients the combination of RT with cetuximab or bevacizumab seems feasible but with higher reported side effects. Patients’ age should not limit the association of trastuzumab and RT in HER2 positive breast cancer. The concurrent administration of TKIs and RT appears to be feasible and effective. Regarding the Immune Check Point inhibitors and RT, tolerance seems similar among older and younger people but definitive data are lacking. Instead, the association of RT and vismodegib/sonidegib remains investigational. Conclusion TT/IT in association of RT seems to be safe, but in elderly patients data concerning safety and toxicity are limited. Specific clinical trials on this population are encouraged.

(1) Aim: To test the performance of a deep learning algorithm in discriminating radiation therapy-related pneumonitis (RP) from COVID-19 pneumonia. (2) Methods: In this retrospective study, we enrolled three groups of subjects: pneumonia-free (control group), COVID-19 pneumonia and RP patients. CT images were analyzed by mean of an artificial intelligence (AI) algorithm based on a novel deep convolutional neural network structure. The cut-off value of risk probability of COVID-19 was 30%, values higher than 30% were classified as COVID-19 High Risk, and values below 30% as COVID-19 Low Risk. The statistical analysis included the Mann–Whitney U test (significance threshold at p &lt, 0.05) and receiver operating characteristic (ROC) curve, with fitting performed using the maximum likelihood fit of a binormal model. (3) Results: Most patients presenting RP (66.7%) were classified by the algorithm as COVID-19 Low Risk. The algorithm showed high sensitivity but low specificity in the detection of RP against COVID-19 pneumonia (sensitivity = 97.0%, specificity = 2%, area under the curve (AUC = 0.72). The specificity increased when an estimated COVID-19 risk probability cut-off of 30% was applied (sensitivity 76%, specificity 63%, AUC = 0.84). (4) Conclusions: The deep learning algorithm was able to discriminate RP from COVID-19 pneumonia, classifying most RP cases as COVID-19 Low Risk.

Simple Summary Proximity to major vessels increases risk of local recurrence in soft tissue sarcomas of the thigh. When major vessels were observed to be surrounded by the tumor on preoperative MRI, vascular resection and by-pass reconstruction offered a better local control. Abstract The aim of this study was to establish the prognostic effects of the proximity of the tumor to the main vessels in patients affected by soft tissue sarcomas (STS) of the thigh. A total of 529 adult patients with deeply seated STS of the thigh and popliteal fossa were included. Vascular proximity was defined on MRI: type 1 > 5 mm; type 2 ≤ 5 mm and >0 mm; type 3 close to the tumor; type 4 enclosed by the tumor. Proximity to major vessels type 1–2 had a local recurrence (LR) rate lower than type 3–4 (p < 0.001). In type 4, vascular by-pass reduced LR risk. On multivariate analysis infiltrative histotypes, high FNLCC grade, radiotherapy administration, and type 3–4 of proximity to major vessels were found to be independent prognostic factors for LR. We observed an augmented risk of recurrence, but not of survival as the tumor was near to the major vessels. When major vessels were found to be surrounded by the tumor on preoperative MRI, vascular resection and bypass reconstruction offered a better local control.

BackgroundThe choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC.MethodsPreoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction.ResultsIncreased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p 418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059).ConclusionsIn R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.

Simple Summary Many classifications to assess margins status for soft tissue sarcomas are reported in the literature. Most of the series are heterogeneous and variable in size, making it difficult to compare results from study to study. Thus, which is the best way to assess margins in order to predict the risk of local recurrence is still debated. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with soft tissue sarcomas (STS). Abstract Adequacy of margins must take into consideration both the resection margin width (quantity) and anatomic barrier (quality). There are several classification schemes for reporting surgical resection margin status for soft tissue sarcomas (STS). Most of the studies regarding treatment outcomes in STS included all histologic grades and histological subtypes, which include infiltrative and non-infiltrative subtypes and are very heterogeneous in terms of both histologic characteristics and treatment modalities (adjuvant treatments or not). This lack of consistency makes it difficult to compare results from study to study. Therefore, there is a great need for evidence-based standardization concerning the width of resection margins. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with STS. Patient cases should be discussed at multidisciplinary tumor boards and treatments should be individualized to clinical and demographic characteristics, which must include also a deep knowledge of specific histotypes behaviors, particularly infiltrative ones.

Opinion statement New molecular insights are being achieved in synovial sarcoma (SS) that can provide new potential diagnostic and prognostic markers as well as therapeutic targets. In particular, the advancement of research on epigenomics and gene regulation is promising. The concrete hypothesis that the pathogenesis of SS might mainly depend on the disruption of the balance of the complex interaction between epigenomic regulatory complexes and the consequences on gene expression opens interesting new perspectives. The standard of care for primary SS is wide surgical resection combined with radiation in selected cases. The role of chemotherapy is still under refinement and can be considered in patients at high risk of metastasis or in those with advanced disease. Cytotoxic chemotherapy (anthracyclines, ifosfamide, trabectedin, and pazopanib) is the treatment of choice, despite several possible side effects. Many possible drug-able targets have been identified. However, the impact of these strategies in improving SS outcome is still limited, thus making current and future research strongly needed to improve the survival of patients with SS.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in women (7%) and the sixth in men (5%) in Italy, with a life expectancy of around 5% at 5 years. From 2010, the Italian Association of Medical Oncology (AIOM) developed national guidelines for several cancers. In this report, we report a summary of clinical recommendations of diagnosis, treatment and follow-up of PDAC, which may guide physicians in their current practice. A panel of AIOM experts in upper gastrointestinal cancer malignancies discussed the available scientific evidence supporting the clinical recommendations.

Aim Aim of this analysis is to review the role of RT in the management of several rare tumors for adult patients. Methods Collection data regarding RT and rare tumors was made by Pubmed. Results For mucosal melanomas, RT is prescribed, being associated with lower local recurrence rate. For trachea tumors, RT was used as adjuvant or salvage treatment for unresectable disease. For pNET, RT can be a suitable option for post-surgical or unresectable/borderline. For bronchopulmonary neuroendocrine tumors the role of adjuvant treatments is uncertain. For hepatobiliary and ovarian malignancy, stereotactic body RT (SBRT) is a promising approach. For soft tissue sarcoma, perioperative treatments are indicated, and a growing role of SBRT in oligometastatic disease is recognized. For endocrine tumors, adjuvant RT has demonstrated benefits through reducing recurrence risk. Conclusion The radiotherapy is a frequent indication in adult rare cancers; thus the role of Radiation Oncologist must not be neglected.

New RT techniques and data emerging from follow-up for several tumor sites suggest that treatment volume de-escalation may permit to minimize therapy-related side effects and/or obtain better clinical outcomes. Here, we summarize the main evidence about volume de-escalation in RT. The relevant literature from PubMed was reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. In Lymphoma, large-volume techniques (extended- and involved-field RT) are being successfully replaced by involved-site RT and involved-node RT. In head and neck carcinoma, spare a part of elective neck is controversial. In early breast cancer, partial breast irradiation has been established as a treatment option in low-risk patients. In pancreatic cancer stereotactic body radiotherapy may be used to dose escalation. Stereotactic radiosurgery should be the treatment choice for patients with oligometastatic brain disease and a life expectancy of more than 3 months, and it should be considered an alternative to WBRT for patients with multiple brain metastases. Further clinical trials are necessary to improve the identification of suitable patient cohorts and the extent of possible volume de-escalation that does not compromise tumor control.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level &gt, 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66&ndash, 19.47, p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64&ndash, 57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9&ndash, 10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (&gt, 90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.

Background: The aim of this retrospective study is to verify whether preoperative systemic inflammatory markers (serum C-reactive protein [CRP] and neutrophil-lymphocyte ratio [NLR]) can help in predicting the disease-specific survival (DSS) and local recurrence (LR) rate in adult patients affected by localized myxofibrosarcoma (MFS) of the extremities. Methods: We reviewed 126 adult patients with primary, localized MFS of the limbs. We analyzed DSS and LR. Results: Median age at the time of surgery was 68 years (range 19–92). Median CRP was 0.4 mg/dL and median NLR was 2.8. A worse DSS was found in patients who had preoperative CRP >0.5 mg/dL (p = 0.002) and in those with NLR >3.5 (p < 0.001). In multivariate analysis, tumor size and grade as well as preoperative CRP values and NLR were confirmed to be prognostic factors in terms of DSS. An increased risk of LR was found in multivariate analysis in patients with a tail sign and with high gadolinium enhancement at preoperative MRI. Conclusions: Patients with high preoperative CRP and NLR levels, as well as large and high-grade tumors, might be considered as candidates for additional, more aggressive treatment approaches or more stringent follow-up schedules.

Aim: To evaluate the efficacy of a propolis-based syrup, FARINGEL®, in preventing radiation-induced esophagitis in locally advanced lung cancer patients. Methods. Patients were treated with concurrent chemoradiotherapy (CRT) using involved-field radiotherapy (RT). Every patient received FARINGEL at the beginning of CRT until the first follow-up. The data of the study group were compared with the data of a control group treated without the administration of the syrup. Results: Forty-five patients were enrolled. Forty-one (91.1%) completed the protocol and were evaluable for esophagitis. Grade ≥2 toxicity occurred in 9/41 patients (22%). No differences in overall toxicity were detected between the study group and the control group (n = 55, 60.9 vs. 54.5%; p = ns). Grade 2–3 esophagitis was lower in the study group in comparison with the control group (22 and 38%, respectively), but statistical significance was not reached (p = 0.09). However, the onset of grade ≥2 esophagitis was delayed in the study group compared to the control group, occurring at higher doses of RT (41.8 vs. 25.4 Gy; p < 0.001). Furthermore, the mean number of interruption days for esophagitis was lower in the study group than in the control group (0.6 ± 2.0 vs. 2.1 ± 3.6; p = 0.025). Conclusion: FARINGEL was well-tolerated and delayed esophagitis that was induced by CRT for locally advanced lung cancer.

Introduction Anatomical change of tumor during radiotherapy contributes to target missing. However, in the case of tumor shrinkage, adaptation of volume could result in an increased incidence of recurrence in the area of target reduction. This study aims to investigate the incidence of failure of the adaptive approach and, in particular, the risk for local recurrence in the area excluded after replanning. Methods In this prospective study, patients with locally advanced NSCLC treated with concomitant chemoradiation underwent weekly chest computed tomography simulation during treatment. In the case of tumor shrinkage, a new tumor volume was delineated and a new treatment plan outlined (replanning). Toxicity was evaluated with the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Patterns of failures were classified as in field (dimensional and/or metabolic progression within the replanning planning target volume [PTV]), marginal (recurrence in initial the PTV excluded from the replanning PTV), and out of field (recurrence outside the initial PTV). Results Replanning was outlined in 50 patients selected from a total of 217 patients subjected to weekly simulation computed tomography in our center from 2012 to 2014. With a median follow-up of 20.5 months, acute grade 3 or higher pulmonary and esophageal toxicity were reported in 2% and 4% of cases and late toxicity in 4% and 2%, respectively. Marginal relapse was recorded in 6% of patients, and 20% and 4% of patients experienced in-field and out-of-field local failure, respectively. Conclusions The reduced toxicity and the documented low rate of marginal failures make the adaptive approach a modern option for future randomized studies. The best scenario to confirm its application is probably in neoadjuvant chemoradiation trials.

Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity.

Introduction: Targeted therapies against epidermal growth factor receptor (EGFR) have revolutionized the treatment of a subset of lung adenocarcinomas that have EGFR-activating mutations; however, all patients treated with EGFR tyrosine kinase inhibitors (TKIs) ultimately develop resistance. Histologic transformation of EGFR-mutant adenocarcinoma to small cell lung cancer (SCLC) is a resistance mechanism rarely reported in the literature. Case presentation: We describe the case of a woman with metastatic lung cancer adenocarcinoma with mutated EGFR with an initial response to gefitinib and radiation therapy, who progressed after 18 months due to the development of a resistance mechanism. The new biopsy performed after progression highlighted histologic transformation to SCLC, while maintaining the original EGFR mutation. Conclusions: To better identify patients who progress after TKIs and radiation therapy, it is important to perform tumor rebiopsy and collect data to study mechanisms of acquired EGFR TKI resistance.

Aim Functional and molecular imaging, including positron emission tomography with computed tomography imaging (PET/CT) is increasing for radiotherapy (RT) definition of the target volume. This expert review summarizes existing data of functional imaging modalities and RT management, in terms of target volume delineation, for the following anatomical districts: brain (for primary and secondary tumors), head/neck and lung. Materials and methods A collection of available published data was made, by PubMed a search. Only original articles were carefully and critically revised. Results For primary and secondary brain tumors, amino acid PET radiotracers could be useful to identify microscopic residual areas and to differ between recurrence and treatment-related alterations in case of re-irradiation. As for head and neck neoplasms may benefit from precise PET/CT-based target delineation, due to the major capability to identify high-risk RT areas. In primary and secondary lung cancer, PET/CT could be useful both to delimit a tumor and collapsed lungs and as a predictive parameter of treatment response. Conclusion Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Nevertheless, several uncertainties remain on the standard method to properly assess the target volume definition including PET information for primary and secondary brain tumors.

In order to evaluate neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) in predicting response and complications in rectal cancer patients who underwent surgery after neo-adjuvant radio-chemotherapy, 87 patients were evaluated. Cutoffs before and after radio-chemotherapy were respectively 2.8 and 3.8 for NLR, and 1.4 and 2.3 for d-NLR. They were analyzed in relation to clinical and pathological outcomes. Patients with preoperative NLR and d-NLR higher than cutoffs had significantly higher rates of tumor regression grade response (TRG ≥ 4) and postoperative complications. Elevated NLR and d-NLR after radio-chemotherapy are associated with worse pathological and clinical outcome.