Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

BACKGROUND: Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. METHODS: This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). RESULTS: Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5 months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). CONCLUSION: In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Disease course of lung oligometastatic colorectal cancer treated with stereotactic body radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) has been shown to increase survival rates in oligometastatic disease (OMD), but local control of colorectal metastases remains poor. We aimed to explore the natural course of oligometastatic colorectal cancer and to investigate how SBRT of lung metastases can delay the progression to polymetastatic disease (PMD). METHODS: 107 lung oligometastases in 38 patients were treated with SBRT at a single institution. The median number of treated lesions was 2 (range 1-5). Time to PMD (ttPMD) was defined as the time from SBRT to the occurrence of >5 new metastases. Genetic biomarkers such as EGFR, KRAS, NRAS, BRAF, and microsatellite instability were investigated as predictive factors for response rates. RESULTS: Median follow-up was 28 months. At median follow-up, 7 patients were free from disease and 31 had progression: 18 patients had sequential oligometastatic disease (SOMD) and 13 polymetastatic progression. All SOMD cases received a second SBRT course. Median progression-free survival (PFS) was 7 months (range 4-9 months); median ttPMD was 25.8 months (range 12-39 months) with 1­ and 2­year PFS rates of 62.5% and 53.4%, respectively. 1­ and 2­year local PFS (LPFS) rates were 91.5% and 80%, respectively. At univariate analysis, BRAF wildtype correlated with better LPFS (p = 0.003), SOMD after primary SBRT was associated with longer cancer-specific survival (p = 0.031). Median overall survival (OS) was 39.5 months (range 26-64 months) and 2­year OS was 71.1%. CONCLUSION: The present results support local ablative treatment of lung metastases using SBRT in oligometastatic colorectal cancer patients, as it can delay the transition to PMD. Patients who progressed as SOMD maintained a survival advantage compared to those who developed PMD.

The linguistic validation process of the Vanderbilt Head and Neck Symptom Survey - Italian Version (VHNSS-IT).

PURPOSE: To linguistically validate the Italian translation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), there is a patient-reported outcome measure to screen for symptoms in the head and neck cancer (HNC) patients population. The goal was to ensure conceptually equivalence with the original version and maintain clarity, ease of use and understanding. METHODS: We conducted a multi-step linguistic process (forward translation, backward translation and patient testing) to generate and validate an Italian translation of the VHNSS. RESULTS: Two intermediate Italian versions were created: The first Italian version was derived from a reconciliation of the three forward translations, and the second Italian version was derived from changes in the first version after the backward translation step. All investigators involved actively discussed possible solutions to produce a translated instrument that maintained a reading and comprehension level accessible by most respondents, without altering the meaning and content of the original source. During the patient testing step, only two patients reported problems with items comprehension and the rate of comprehension problems per single item was lower than expected. This phase allowed patients to give suggestion in order to make items clearer and easier to understand: 43% of patients proposed a revision of the survey during the face-to-face interview, and most of these suggestions were retained. CONCLUSIONS: A valid multi-step process leads to the creation of the final version of the VHNSS-IT, a suitable instrument to screen for symptoms in the Italian HNC patients population and an official measurement tool that can be used in cooperative research group.

A pilot study on the Vanderbilt head and neck symptom survey Italian version (VHNSS-IT) to test its feasibility and utility in routine clinical practice.

PURPOSE: Patient-reported outcome measures can be useful to assess symptoms in head and neck cancer (HNC) patients treated with radio-chemotherapy. This is a pilot study on the VHNSS-IT (the Italian version of the Vanderbilt head and neck symptom survey) performed to assess both the feasibility and utility of its administration in clinical practice. METHODS: The outcomes analyzed were feasibility to recruit patients, feasibility to complete the questionnaire, feasibility to review the questionnaire, utility perceived by clinicians, distribution of patient's answers reflecting symptom's intensity. RESULTS: Among the 38 patients enrolled, 37 completed the VHNSS-IT (refusal rate 2.6%). Median time of completion was 6'57″. Time of completion was influenced by age (p = 0.002), grade of education (p = 0.023) and employment status (p = 0.004). Time after the start of the radiotherapy course (< 6 months vs. > 6 months) and surgery (yes vs. no) influenced symptoms' intensity. Median time for review was 2'15″. Time burden was perceived to be acceptable for all clinicians; they all also found the questionnaire easy to use. Rates of global perceived utility and future intention to use the questionnaire were 100%. CONCLUSIONS: The VHNSS-IT has demonstrated to be a useful measurement of symptoms' burden for patients with HNC. The survey can be easily completed during the clinic routine without interfering with doctors' visits schedule, and it can help healthcare providers to identify symptoms that require referral, education or intervention.

Overexpression of sialidase NEU3 increases the cellular radioresistance potential of U87MG glioblastoma cells.

The plasma membrane-associated sialidase NEU3 is known to play important roles in different physiological and pathophysiological processes such as proliferation, cellular differentiation and tumorigenesis. Up-regulation of NEU3 has been associated to several tumors and recently it was demonstrated that its down-modulation in glioblastoma cells promotes cell invasiveness. To date, no information concerning the possible role played by NEU3 in relation to tumor radioresistance is available. Here we show that overexpression of NEU3 in glioblastoma U87MG cells activates PI3K/Akt signaling pathway resulting in an increased radioresistance capacity and in an improved efficiency of double strand DNA-repair mechanisms after irradiation. Our results demonstrate for the first time that NEU3 contributes to the radioresistance features of U87MG cells, bringing to evidence a novel rand peculiar role of the enzyme in cancer biology.

Long-Term Outcomes of Immunohistochemically Defined Subtypes of Breast Cancer Less Than or Equal to 2 cm After Breast-Conserving Surgery.

BACKGROUND: Molecular subtype predicts the prognosis of early-stage breast cancer patients. We assessed the long-term outcomes of breast cancer ≤2 cm treated with breast-conserving surgery (BCS) and stratified according to an immunohistochemically (IHC)-based subtype definition. METHODS: This retrospective study was conducted from a prospectively collected database. Included patients had pT1, any N, M0 breast cancer after BCS (without anti-HER2 therapy) and available information on estrogen receptor (ER), progesterone receptor (PR), HER2 status, Ki-67 index. Five IHC-defined subtypes were identified: luminal A-like (ER and/or PR-positive/HER2-negative/Ki-67 < 20%), luminal B-like/HER2-negative (ER and/or PR-positive/HER2-negative/Ki-67 ≥ 20%), luminal B-like/HER2-positive (ER and/or PR-positive/HER2-positive/any Ki-67 value), HER2-positive/nonluminal (ER and PR-negative/HER2-positive), and triple-negative (ER and PR-negative/HER2-negative). RESULTS: We analyzed 184 (65%) luminal A-like, 57 (20%) luminal B-like/HER2-negative, 17 (6%) luminal B-like/HER2-positive, 6 (2%) HER2-positive/nonluminal, and 18 (7%) triple-negative patients. Median follow-up was 112 (interquartile range 94-125) mo. The cumulative 5- and 10-y local recurrence (LR) rates were 1.5% and 4%, respectively. The cumulative 5- and 10-y distant recurrence (DR) rates were 3% and 8%, respectively. The Cox regression revealed that HER2-positive/nonluminal subtypes had the highest risk of LR (P = 0.0025). The luminal B-like/HER2-positive subtypes had the highest risk of DR (P = 0.0019). HER2 positivity carried a higher risk of DR in women with luminal breast cancer who completed 5 y of adjuvant hormonal therapy (P = 0.02). CONCLUSIONS: The IHC-defined subtype impacts on the prognosis of breast cancer ≤2 cm after BCS, determining significant differences in LR and DR rates. In the pre-"anti-HER2 therapy" era, patients with HER2-positive/nonluminal or luminal B-like/HER2-positive subtype had worse long-term outcomes than those with luminal A-like subtype.

Applying radiation protection and safety in radiotherapy.

Radiotherapy is one of the primary treatment options in cancer management. Modern radiotherapy includes complex processes requiring many different kinds of expertise. Among them, knowledge and skills are needed in clinical oncology, radiobiology, radiotherapy planning and simulation, dose measurement and calculation, radiation safety and medical physics. Radiation oncologists should assume the full and final responsibility for treatment, follow-up and supportive care of the patient. For all these activities, radiation oncologist should coordinate and collaborate with a team including different professionals: nurses, radiographers (RTT), clinical engineers, information system experts, taking advantage in particular of the dosimetry expertise of the medical physicist. Radiation therapy is widely recognized to be one of the safest areas of modern medicine, and errors are very rare. However, radiation protection recommendations developed at national level should comply with the EURATOM Directive 2013/59. This paper describes several contemporary and emerging concerns related to radioprotection in radiation therapy including quality and safety in external beam radiotherapy and brachytherapy, foetal dose, secondary malignancies, and the safety issues related to the new techniques and treatment strategies.

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study.

BACKGROUND: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC). METHODS: Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1-3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients. RESULTS: About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design. CONCLUSIONS: Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Clinical outcomes and toxicity after exclusive versus postoperative radiotherapy in supraglottic cancer: new solutions for old problems? The case of stage III and IV disease.

PURPOSE: To compare toxicity, survival and laryngeal preservation rate after radiotherapy alone (RR), radiotherapy after supraglottic horizontal laryngectomy (SHLR) and radiotherapy after total laryngectomy (TLR) for advanced supraglottic laryngeal cancer. MATERIALS AND METHODS: From 1984 to 2012, 532 patients (pts) were treated in our Department: 273 were potentially fit for conservative surgery (Group I) and 259 were not amenable to partial surgery (Group II). RESULTS: A younger age (p = 0.005), a better performance status (p < 0.001), the absence of comorbidities (p < 0.001) and the absence of nodal involvement (p = 0.006) favorably impacted on overall survival. More high-grade mucositis (p = 0.009), mild dysphagia (p < 0.001) and mild xerostomia (p < 0.001) were found in RR group; surgical patients had more edema of neck (p = 0.009) and skin toxicity (p = 0.008). Group I No differences in local, nodal and distant recurrences and in number of rescue laryngectomies were observed. The disease characteristics (T, N and stage) but not the treatment modality impacted on disease-free survival (DFS). Group II There was an higher number of local (p = 0.013) and nodal (p = 0.022) recurrences after RR. DFS (p = 0.01) was longer after TLR. No differences in DFS between TLR patients and RR patients who underwent radio-chemotherapy were found. CONCLUSION: In Group I, RR results in a local-regional control and organ preservation comparable to surgical treatments, with only slight increase of late mild xerostomia and dysphagia. In Group II RR was less effective than TLR, with a significantly worse DFS. The use of concurrent radical radio-chemotherapy seems to provide comparable loco-regional control to TLR.

Resected pN1 non-small cell lung cancer: recurrence patterns and nodal risk factors may suggest selection criteria for post-operative radiotherapy.

PURPOSE: To describe the pattern of recurrence in resected pN1 non-small cell lung cancer (NSCLC) and to identify factors predicting an increased risk of locoregional recurrence (LR) or distant metastasis (DM) to define a selected population who may benefit from postoperative radiotherapy (PORT). METHODS: 285 patients with resected pN1 NSCLC were identified. Patients with positive surgical margins, undergoing neoadjuvant treatment or PORT, were excluded. LR was defined as first event of recurrence at the surgical bed, ipsilateral hilum or mediastinum, and other sites were considered as DM. Kaplan-Meier actuarial estimates of overall survival (OS), progression-free survival (PFS), freedom from LR (FFLR) and freedom from DM (FFDM) in different subgroups were compared with the log-rank test. Multivariate analysis was calculated. RESULTS: 202 patients met the inclusion criteria, 24 % received adjuvant chemotherapy. The median follow-up was 39 months. The total number of recurrences was 118 (64.4 %): 44 (24 %) and 74 (40.4 %) for LR and DM, respectively. Five-year OS and PFS rates were 39.2 and 33.3 %, respectively. Extra capsular extension (ECE) (RR 2.10, p = 0.01) and lymph nodal ratio (LNR) >0:15 (RR 1.68, p = 0.015) were associated with a worse PFS. ECE and LNR >0.15 were significantly related to a worst FFLR (RR 3.04 and 4.42, respectively), and adenocarcinoma to an unfavorable FFDM (RR 1.97, p = 0.013). CONCLUSIONS: Nodal factors as high LNR and ECE can predict an increased risk of worse FFLR and PFS. Prospective data on selected patients, treated with modern radiotherapy techniques, need to be collected to re-evaluate the role of radiotherapy.

Clinical outcomes and toxicity after exclusive versus postoperative radiotherapy in supraglottic cancer: new solutions for old problems? The case of stage I and II disease.

PURPOSE: To compare acute and late toxicities, survival, and laryngeal preservation after radiotherapy alone (RR) or radiotherapy after partial laryngectomy (PLR) in early supraglottic laryngeal cancer. MATERIALS AND METHODS: From 1984 to 2012, 172 patients were treated in our department. We analyzed and compared toxicities (CTCAE v 4.0), overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), metastasis-free survival (MFS), and the number of salvage total laryngectomies. RESULTS: Patients in the RR group were older (p = 0.05) and had more often comorbidities (p = 0.025); those in the PLR group had mostly T2 disease (p = 0.014). No difference in number of local, nodal, and distant recurrences was found. A higher incidence of late mild dry mouth in patients treated with RR (38 vs. 4 %, p = 0.000) was reported. At univariate analysis, only a younger age, a better performance status, and the absence of comorbidities favorably impacted on OS and DSS. No differences were found in DFS, LRFS, NRFS, MFS, and the number of rescue laryngectomies between the two groups. Younger age and a good performance status persisted as a predictive factor of better survival (OS and DSS) at multivariate analysis. CONCLUSION: Radical radiotherapy appears to be a viable alternative to conservative surgery, even in elderly patients with poor performance status and comorbidities. Salvage laryngectomy in the RR group was compared favorably with those reported in other conservative surgery series and in the group treated postoperatively of our series.

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis.

AIM: To evaluate the efficacy of whole brain radiotherapy (WBRT) with or without other treatments in patients (pts) with 1-3 brain metastases (BM). MATERIALS AND METHODS: Toxicities and survival of 134 pts treated between 2009 and 2013 with WBRT alone (58 pts), WBRT plus surgery (SUR-WBRT: 42 pts) or WBRT followed by stereotactic or integrated boost radiotherapy (SRT-WBRT: 34 pts) were analyzed. Differences in toxicity (acute and late) incidence and in overall (OS), disease-free (DFS) and disease-specific survival (DSS) were evaluated (χ(2)-test, uni- and multivariate analysis). RESULTS: Pts given intensified treatments (SUR- and SBRT-WBRT) had better 3-month local response compared to WBRT alone group (p < 0.045). Better 1-year local control was evident only in SRT-WBRT pts (p < 0.035). Univariate OS analysis confirmed, as favorable prognostic factors, RPA class I (p < 0.001), GPA class III and IV (p < 0.001), single metastasis (p = 0.045), stable primary disease (p = 0.03), intensified treatment (p = 0.000), systemic therapy after radiotherapy (p = 0.04) and response of metastatic lesions (p = 0.002). At multivariate analysis, OS was better in RPA class I pts (p = 0.002), who had more aggressive radiotherapy treatments (p = 0.001), chemotherapy after radiotherapy (p < 0.001) and response to RT (p = 0.003). Response to radiotherapy (p = 0.002) and BM number (p < 0.001) resulted independently prognostic for DFS. About 60 % of patients had mild acute toxicity (G1), especially headache (51 %) and fatigue (34 %); only 2 patients (2 %) had severe (G3) headache and 5 patients (4 %) severe fatigue (G3) reversible with oral steroids. No differences were evident between the different treatment groups. Among 80 pts followed up with MRI, 12 (15 %) had leukoencephalopathy (equally distributed across subgroups) and 5 (6 %) radionecroses, 4/5 asymptomatic, 5/5 in pts given intensified treatments. CONCLUSIONS: This analysis confirms the known prognostic factors for BM, emphasizing the importance of intensified treatments in a population with favorable features.

Radiotherapy for adult medulloblastoma: Long term result from a single institution. A review of prognostic factors and why we do need a multi-institutional cooperative program.

AIM: We retrospectively analyzed our Institution experience with these patients. The endpoints of the analysis were overall survival (OS), disease-free survival (DFS), local control (LC), metastasis free survival (MFS); results were compared with the literature. BACKGROUND: Medulloblastoma in adult patients is a very rare disease; the 5 and 10-year overall survival rates range between 33-78% and 27-56%, respectively. The collection of more clinical data is strongly needed. MATERIALS AND METHODS: From September 1975 to October 2006, we treated 16 adult patients (9 males and 7 females) with a histological diagnosis of medulloblastoma. Acute and late toxicities were scored according to RTOG toxicity scale. Karnofski performance status (KPS) and neurological performance status (NPS) pre- and post-RT were reported. Median age was 27 years (range 18-53 years). All the patients received cranio-spinal irradiation, two patients were also given chemotherapy. Median follow-up period was 121.5 months. RESULTS: In January 2014, 10/16 patients were alive without evidence of disease, 6/16 died with progressive disease (1 local and spinal, 3 spinal and 2 extraneural). Ten-year LC, OS, DFS, MFS were, respectively, 84%, 67%, 60% and 59%. Univariate analysis shows that gross total resection is associated with better survival. No acute or late G3-G4 toxicity was observed. CONCLUSIONS: This experience and the analysis of the literature confirm the efficacy of postoperative RT but also the need of large datasets to better define prognostic factors and the possible role of the association of chemotherapy.

The role of radiation therapy in the multidisciplinary management of male breast cancer: a systematic review and meta-analysis.

Male breast cancer (MaBC) is an uncommon disease. It is generally assimilated to post-menopausal female breast cancer and treated accordingly. However, the real impact of radiation therapy, after both mastectomy and breast conservation, has yet to be established. We performed a systematic review and meta-analysis to assess the clinical impact of radiation therapy in MBC patients to support the clinical decision-making process and to inform future research. We performed a systematic search of 'male', 'breast', 'cancer', 'radiotherapy' and corresponding synonyms on PubMed/MEDLINE and EMBASE databases. We included interventional studies reporting on radiation therapy effect on overall survival (OS) in MBC patients. Reviews, editorials, letters to the editor, conference abstracts and case reports, and studies with less than 20 MaBC patients or without data on OS were excluded. We extracted relevant characteristics and outcomes for each study, including the hazard ratio (HR) for OS, after adjustment for potential confounders. We calculated an overall adjusted hazard ratio (aHR) for OS for patients receiving radiation therapy compared to those who did not. A random effect model was used. The search strategy yielded 10,260 articles. After removal of duplicates (n = 8,254), 2,006 articles remained and underwent abstract screening. A total of 168 manuscripts was selected for full text screening. After full text screening, 22 articles were included in the qualitative systematic review. Among them, 14 were included in the quantitative synthesis, reporting on 80.219 MaBC patients. A statistically significant reduction in the risk of death was observed for patients receiving radiation therapy, with a pooled aHR = 0.73 (95%CI: 0.66-0.81) for OS. Significant heterogeneity among reported aHR estimates was seen (I2=77%). A significant clinical benefit on OS has been observed when including radiation therapy in the therapeutic algorithm of patients with MaBC. These findings, which are based on retrospective studies and tumour registry reports, deserve further investigation to identify MaBC patient subgroups who most benefit from radiation therapy.

Axillary Management in Breast Cancer Patients Undergoing Upfront Surgery: Results from a Nationwide Survey on Behalf of the Clinical Oncology Breast Cancer Group (COBCG) and the Breast Cancer Study Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

BACKGROUND: We assessed the current practice concerning the axillary management of breast cancer (BC) patients undergoing upfront surgery among radiation oncologists (ROs) practising in Italy. METHODS: An online survey via SurveyMonkey (including 21 questions) was distributed amongst ROs in Italy through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network from August to September 2022. We particularly focused on the emerging omission of axillary lymph node dissection (ALND) in the presence of 1-2 sentinel node-positive patients and the consequent change in the role of regional nodal irradiation (RNI). RESULTS: A total of 101/195 (51% response rate) Italian Radiotherapy Cancer Care Centres answered the survey. With respect to patients with 1-2 sentinel node-positive, the relative proportion of respondents that offer patients ALND a) always, b) only in selected cases, and c) never was 37.6%, 60.4%, and 2.0%, respectively, with no significant geographical (North vs. Centre-South Italy; p = 0.92) or institutional (Academic vs. non-Academic; p = 0.49) differences. Radiation therapy indications varied widely in patients who did not undergo ALND. Among these, about a third of the respondents (17/56, 30.4%) stated that RNI was constantly performed. On the other hand, half of the respondents offered RNI in selected cases, stating that an unfavourable biologic tumour profile and extracapsular nodal extension were considered drivers of their decision. CONCLUSIONS: Results of the present survey show the variability of axillary management offered in clinical practice for BC patients undergoing conserving surgery upfront in Italy. Analysis of these attitudes may trigger the modification of some clinical approaches through multidisciplinary collaboration and create the background for future clinical investigations.

Prognostic Role of Pre-Treatment Metabolic Parameters and Sarcopenia Derived by 2-[18F]-FDG PET/CT in Elderly Mantle Cell Lymphoma.

The goal of this retrospective study was to analyze and compare the prognostic role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT) features and sarcopenia, estimated by CT of PET in elderly (≥65 years) Mantle Cell Lymphoma (MCL). We recruited 53 patients, who underwent pre-treatment 2-[18F]-FDG PET/CT and end-of-treatment PET/CT, and the main semiquantitative parameters were calculated. Sarcopenia was measured as skeletal muscle index (SMI, cm2/m2) and derived by low-dose PET/CT images at the L3 level. Specific cut-offs for SMI were calculated by receiver operator curve and divided by gender. Metabolic response was evaluated at end-of-treatment PET/CT, applying the Deauville score. Progression Free Survival (PFS) and Overall Survival (OS) were calculated for the whole population and for different subgroups, defined as per different sarcopenia cut-off levels. The specific cut-offs to define sarcopenia were 53 cm2/m2 for male and 45.6 cm2/m2 for female. Thirty-two (60%) patients were defined as sarcopenic. The 3-year and 5-year PFS rates were 29% and 23%, while the 3-year and 5-year OS rates were 43% and 33%. Metabolic response, total metabolic tumor volume (tMTV), total lesion glycolysis (tTLG) and sarcopenia were independent prognostic factors for PFS. Considering OS, no variable was significantly associated. Combination between PET features and sarcopenia may help to predict PFS.

Comparison between Two Different Scanners for the Evaluation of the Role of 18F-FDG PET/CT Semiquantitative Parameters and Radiomics Features in the Prediction of Final Diagnosis of Thyroid Incidentalomas.

The aim of this study was to compare two different tomographs for the evaluation of the role of semiquantitative PET/CT parameters and radiomics features (RF) in the prediction of thyroid incidentalomas (TIs) at 18F-FDG imaging. A total of 221 patients with the presence of TIs were retrospectively included. After volumetric segmentation of each TI, semiquantitative parameters and RF were extracted. All of the features were tested for significant differences between the two PET scanners. The performances of all of the features in predicting the nature of TIs were analyzed by testing three classes of final logistic regression predictive models, one for each tomograph and one with both scanners together. Some RF resulted significantly different between the two scanners. PET/CT semiquantitative parameters were not able to predict the final diagnosis of TIs while GLCM-related RF (in particular GLCM entropy_log2 e GLCM entropy_log10) together with some GLRLM-related and GLZLM-related features presented the best predictive performances. In particular, GLCM entropy_log2, GLCM entropy_log10, GLZLM SZHGE, GLRLM HGRE and GLRLM HGZE resulted the RF with best performances. Our study enabled the selection of some RF able to predict the final nature of TIs discovered at 18F-FDG PET/CT imaging. Classic semiquantitative and volumetric PET/CT parameters did not reveal these abilities. Furthermore, a good overlap in the extraction of RF between the two scanners was underlined.

Stratification of Oligometastatic Prostate Cancer Patients by Liquid Biopsy: Clinical Insights from a Pilot Study.

We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.

Prognostic role of baseline 18 F-FDG pet/CT in squamous cell carcinoma of the paranasal sinuses.

BACKGROUND: To retrospectively investigate the prognostic role of baseline 18 F-FDG PET/CT in squamous cell carcinoma (SCC) of the paranasal sinuses. METHODS: Clinical features and PET/CT semiquantitative parameters of 49 patients were collected. Anova and Kruskall-Wallis tests were used to assess the relationship between these parameters. Kaplan-Meier, univariate, and multivariate analysis were performed to search for independent prognostic factors for progression free (PFS) and overall survival (OS). RESULTS: Mean PFS was 29.95 months (SD 29.36) with relapse/progression of disease occurring in 18 patients; mean OS was 33.40 (SD 27.78) months with death occurring in 15 patients. Presence of nodal metastasis (14 subjects) was correlated with standardize uptake value (SUV) max, SUVmean, SUV/blood-pool ratio, SUV/liver ratio, metabolic tumor volume, and total lesion glycolysis. SUVmax, SUVmean, and presence of nodal metastasis resulted as independent prognostic factors for OS. CONCLUSION: 18 F-FDG PET/CT semiquantitative parameters confirmed their prognostic role for SCC of paranasal sinuses.

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.