18 F-FET PET/CT in Calcifying Pseudoneoplasm of the Neuraxis : First Case.

ABSTRACT: A 66-year-old man has been treated in a psychiatric department for 4-5 years for a depressive syndrome, which is associated with poor motor initiative, confusional state, and dysosmia. Dynamic 18 F-FET PET/CT showed only faint uptake of radiotracer just above the background on the left frontal calcific lesion. The time-activity curve of the neoplasms showed a descending pattern. After a left fronto-orbitary minicraniotomy surgery, histology examination concluded for a rare calcifying pseudoneoplasm of the neuraxis (CAPNON). To our knowledge, no data are available on the metabolic behavior of CAPNON in 18 F-FET PET/CT. This case highlighted that a faint uptake and descending pattern on dynamic 18 F-FET PET/CT may be helpful in suspected CAPNON before surgery.

Prognostic Score in Radiotherapy Practice for Palliative Treatments (PROPHET) Study for Bone Metastases: An Investigation Into the Clinical Effect on Treatment Prescription.

Purpose: Bone metastases frequently occur during malignant disease. Palliative radiation therapy (PRT) is a crucial part of palliative care because it can relieve pain and improve patients' quality of life. Often, a clinician's survival estimation is too optimistic. Prognostic scores (PSs) can help clinicians tailor PRT indications to avoid over- or undertreatment. Although the PS is supposed to aid radiation oncologists (ROs) in palliative-care scenarios, it is unclear what type of support, and to what extent, could impact daily clinical practice. Methods and Materials: A national-based investigation of the prescriptive decisions on simulated clinical cases was performed in Italy. Nine clinical cases from real-world clinical practice were selected for this study. Each case description contained complete information regarding the parameters defining the prognosis class according to the PS (in particular, the Mizumoto Prognostic Score, a validated PS available in literature and already applied in some clinical trials). Each case description contained complete information regarding the parameters defining the prognosis class according to the PS. ROs were interviewed through questionnaires, each comprising the same 3 questions per clinical case, asking (1) the prescription after detailing the clinical case features but not the PS prognostic class definition; (2) whether the RO wanted to change the prescription once the PS prognostic class definition was revealed; and (3) in case of a change of the prescription, a new prescriptive option. Three RO categories were defined: dedicated to PRT (RO-d), nondedicated to PRT (RO-nd), and resident in training (IT). Interviewed ROs were distributed among different regions of the country. Results: Conversion rates, agreements, and prescription trends were investigated. The PS determined a statistically significant 11.12% of prescription conversion among ROs. The conversion was higher for the residents and significantly higher for worse prognostic scenario subgroups, respectively. The PS improved prescriptive agreement among ROs (particularly for worse-prognostic-scenario subgroups). Moreover, PS significantly increased standard prescriptive approaches (particularly for worse-clinical-case presentations). Conclusions: To the best of our knowledge, the PROPHET study is the first to directly evaluate the potential clinical consequences of the regular application of any PS. According to the Prophet study, a prognostic score should be integrated into the clinical practice of palliative radiation therapy for bone metastasis and training programs in radiation oncology.

AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Rethinking breast cancer follow-up based on individual risk and recurrence management.

Current follow-up policies for early breast cancer aim to detect loco-regional recurrences and manage treatment-related adverse effects. Their "one size fits all" approach does not take into account differences in subtypes at initial diagnosis, individual prognosis and treatments received. They are derived from clinical trials conducted when early detection means - other than mammography - and treatment options were limited. Herein, we address the arguments for re-evaluating current breast cancer follow-up strategies starting from recent advances in breast cancer local and systemic treatments and discussing individual risk of recurrence prediction models, time-adapted imaging and biomarker assessment for disease diagnostic anticipation. This change in perspective would transform breast cancer follow-up into an integrated, multidisciplinary team medical practice. Hence we discuss the important role of patient-centered approaches, but also of general practitioners and other health professionals, in the final promotion of personalized surveillance programs and patient education.

The dosimetric impact of axillary nodes contouring variability in breast cancer radiotherapy: An AIRO multi-institutional study.

AIM: To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT). MATERIALS AND METHODS: 18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed. RESULTS: 17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose. CONCLUSIONS: Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization.

Lymph nodal radiotherapy in breast cancer: what are the unresolved issues?

Introduction: Sentinel lymph node biopsy (SLNB) is the gold standard in invasive breast cancer. Axillary dissection (ALND) is controversial in some presentations.Areas covered: Key questions were formulated and explored focused on four different scenarios in adjuvant axillary radiation management in early and locally advanced breast cancer. Answers to these questions were searched in MEDLINE, PubMed from June 1946 to August 2020. Clinical trials, retrospective studies, international guidelines, meta-analysis, and reviews were explored.Expert opinion: Analysis according to biological disease characteristics is necessary to establish the impact of ALND avoidance in unexpectedly positive SLNB (pN1) in cN0 patients. A low-risk probability of axillary recurrence was observed if axillary radiotherapy (ART) or ALND were offered without impact on outcomes. Adjuvant RNI in pT1-3 pN1 treated with mastectomy or BCS should be proposed in unfavorable disease and risk factors. In ycN0 after NACT, SLNB can be offered in selected cases or ALND should be performed. After SLNB post-NACT (ypN1), ALND and adjuvant radiotherapy are mandatory.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Radiation treatment for adult rare cancers: Oldest and newest indication.

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.

Loco-regional adjuvant radiation therapy in breast cancer patients with positive axillary lymph-nodes at diagnosis (CN2) undergoing preoperative chemotherapy and with complete pathological lymph-nodes response. Development of GRADE (Grades of recommendation, assessment, Development and Evaluation) recommendation by the Italian Association of radiation therapy and Clinical Oncology (AIRO).

OBJECTIVE: To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST). MATERIAL AND METHODS: Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events. RESULTS: Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63-1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events. CONCLUSIONS: Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy.

Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer.

Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs' in vitro and in vivo sensitivity values correspond to patients' responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.

Volume de-escalation in radiation therapy: state of the art and new perspectives.

PURPOSE: 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. METHOD: The relevant literature from PubMed was reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: 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. CONCLUSION: 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.

PAIDEIA: pacemaker and implanted cardioverter defibrillator management in radiation therapy-a survey by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

INTRODUCTION: The management of patients bearing a cardiac implantable electronic device and needing a radiotherapy treatment is an important clinical scenario. The aim of this survey was to evaluate the level of awareness within the Italian Radiation Oncologist community on this topic. MATERIALS AND METHODS: A survey was promoted by the Young Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO) with a questionnaire made up of 22 questions allowing for multiple answers, which was administered, both online and on paper version. It was addressed to Radiation Oncologists, AIRO members, participating in the National Congress held in 2015. RESULTS: A total of 113 questionnaires were collected back and analyzed (survey online: 50 respondents; paper version: 63). The answers showed a good level of awareness on the issue, but with a nonhomogeneous adherence to the different published guidelines (GL). There is a general low rate of referral for a preliminary cardiological evaluation in patients bearing PM/ICDs, in line with some published surveys; nevertheless, a focused attention to certain specific treatment factors and patient-centered point of view emerged. CONCLUSIONS: A generally good awareness of this topic was shown but homogeneous application of GL was not observed, possibly due to the multiplicity of available GL. A prospective data collection could help to better clarify the shadows on this topics.

Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 2.

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.

Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 1.

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.

Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO.

AIM: To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies. METHODS: A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period. RESULTS: A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25-92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45-50 Gy in 25-28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9-10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I-II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%). CONCLUSION: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.

Safety and efficacy of combined radiotherapy, immunotherapy and targeted agents in elderly patients: A literature review.

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.

Evaluation of Italian radiotherapy research from 1985 to 2005: preliminary analysis.

AIM: The difficulty in conducting meaningful clinical research is a multifactorial issue, involving political, financial and cultural problems, which can lead to unexpected negative long-term consequences, in terms of knowledge advancement and impact on patient care. The aims of the present review were to evaluate the publications of Italian radiotherapy (RT) groups during a 20-year period and to verify whether research is still appealing to young radiation oncologists (ROs) in Italy. METHODS: PubMed database was searched for English-language articles published by Italian groups from January 1985 to December 2005. Analyzed variables were: publication/year, kind of study, geographical area and age of the first author. RESULTS: The systematic review identified 3291 articles: 1207 papers fulfilled the inclusion criteria. The number of Italian published papers increased during the examined period. Retrospective analyses, prospective phase I-II trials and literature reviews were 44, 20 and 14.5% of all published manuscripts, respectively. Randomized trials showed a mild increase from 2000 to 2005, but their absolute number remained low respect to other types of studies (4%). Northern Italy produced the very most of Italian research papers (58.7%). The age of the first/second author was evaluated on 716 papers: In more than 50% of cases, the first author was younger than 40. CONCLUSION: Despite a general gradual improvement, RT clinical research suffers in Italy (as elsewhere) from insufficient funding, with a negative impact on evidence production. It is worth noting that clinical research is still appealing and accessible to junior Italian RO.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Combined modality therapy for thoracic and head and neck cancers: a review of updated literature based on a consensus meeting.

PURPOSE: Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial. METHODS: The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress. RESULTS: The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial. CONCLUSIONS: Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.