Stereotactic radiotherapy (SRT) for differentiated thyroid cancer (DTC) oligometastases: an AIRO (Italian association of radiotherapy and clinical oncology) systematic review.

PURPOSE: The aim of this systematic review was to examine efficacy of stereotactic radiotherapy (SRT) in patients with oligometastatic thyroid cancer. MATERIALS AND METHODS: A systematic search was conducted by means of PubMed, Scopus, and Cochrane library. CLINICALTRIALS: gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical studies as full text carried out on patients with oligometastatic thyroid cancer treated with SRT. Conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. Time of publication was restricted to the years 1990-2021. RESULTS: The number of evaluated patients was 146 (267 lesions), and the median age was 58 years. The median 1-year local control (LC) was 82% (range 67.0%-97.1%); the median disease-free survival (DFS) was 12 months (range 4-53); the median 1-year overall survival was 72% (range 66.6%-85.0%); the 3-year cancer-specific survival was 75.0%; and the 4-year cancer-specific survival was 37.5%. No grade 3-5 acute toxicity was reported. No late effects were recorded. CONCLUSIONS: SRT for oligometastases from thyroid cancer as salvage therapy is well tolerated and yields high rates of LC and prolonged DFS.

A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma.

BACKGROUND: The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. METHODS/DESIGN: In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a "total neoadjuvant" therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. TRIAL REGISTRATION: NCT04090463 at clinicaltrials.gov.

Radiotherapy activities and technological equipment in Veneto, Italy: a report from the Rete Radioterapica Veneta.

BACKGROUND: Despite the pivotal role of radiotherapy in oncology, the provision of radiation treatments remains inadequate in many areas of the world. The present report is an assessment conducted among Radiation Oncology centers of Veneto region with the aim to collect information concerning radiotherapy assets and technological equipment availability. METHODS: Data concerning Veneto Radiation Oncology departments about radiotherapy activities, number of treatments, techniques used and radiotherapy machines available were collected. The reference time period was 2018. Reimbursement system databases and business intelligence systems were used. Extra-regional attraction and migration were evaluated. When available, data were compared to previous years. RESULTS: Veneto in 2018 was endowed with 1 megavolt unit for about 153,000 inhabitants. The number of megavolt machines per million inhabitants resulted to be 6.72. In 51% of radiotherapy treatments, intensity-modulated techniques were performed. Six percent of treatments were administered to extra-regional patients. CONCLUSION: Radiotherapy assets and equipment in Veneto seem to be appropriate to standard requests in terms of availability and technology.

Diffuse gliomas in patients aged 55 years or over: A suggestion for IDH mutation testing.

Diffuse gliomas are defined on the isocitrate dehydrogenase (IDH) gene (IDH) mutational mutational status. The most frequent IDH mutation is IDH1 R132H, which is detectable by immunohistochemistry; other IDH mutations are rare (10%). IDH mutant gliomas have better prognosis. Further, IDH wild-type low-grade (II/III) gliomas have clinical behaviors similar to those of glioblastoma (GBM) and it was suggested that they are submitted to similar post-surgical treatment. The incidence of IDH mutant gliomas (2%) and that of GBMs with non-canonical IDH mutations (< 1%) are very low in patients ≥ 55 years. For this reason, it was suggested that immunohistochemistry against IDH1 R132H is sufficient to classify GBM as IDH wild-type in this age group. However, no indication was provided for IDH mutational testing in low-grade diffuse gliomas. To address this issue, 273 diffuse gliomas were tested for IDH1 R132H immunohistochemistry. 2/4 diffuse astrocytomas (DAs), 4/9 anaplastic astrocytomas (AAs), 2/256 GBMs, and 4/4 oligodendrogliomas had positive staining. No other IDH mutations were found in immuno-negative low-grade cases by DNA sequencing. To validate our findings, we considered 311 diffuse gliomas in patients ≥ 55 years in The Cancer Genome Atlas database. Fifty-five out of 311 gliomas had IDH R132H mutations (9/16 DAs; 8/48 AAs; 3/211 GBMs; 35/36 oligodendrogliomas), one DA, and one oligodendroglioma had other IDH mutations. IDH mutant gliomas had significantly higher frequency of O-6-methylguanine-DNA methyltransferase promoter methylation (P = 0.0008) and longer overall survival (P < 0.0001). In conclusion, low-grade gliomas are a minor part of gliomas (117/584) in patients ≥ 55 years, albeit they represent most IDH mutant gliomas in this age group (64/69 cases). IDH non-canonical mutations can be found in immunonegative low-grade gliomas (2/54). In view of its significance for prognosis and therapeutic management, our results suggest that IDH mutational status is assessed in all diffuse gliomas in patients ≥ 55 years by immunohistochemistry, followed by IDH sequencing in low-grade immunonegative cases.

Selective transarterial radioembolisation of unresectable liver-dominant colorectal cancer refractory to chemotherapy.

PURPOSE: The target lesion response (according to the Choi criteria), safety and survival following selective or superselective transarterial radioembolisation using yttrium-90-resin microspheres ((90)Y-RE) were evaluated in patients with unresectable, chemotherapy-refractory colorectal cancer liver metastases (mCRC). MATERIALS AND METHODS: A prospective case series evaluated 52 consecutive patients with mCRC who were treated at a single centre following a median of 2 lines of chemotherapy. RESULTS: Nearly half (46.2 %) of the 52 patients had a prior resection of the liver. At baseline, mCRC was limited to the liver (in 56.9 %), liver plus extra-hepatic metastases (23.5 %) or liver plus lung micro-nodules (19.6 %). Disease control rates of target lesions (partial response plus stable disease) at 3 and 6 months post-(90)Y-RE were 59 and 29 %, respectively. Target lesions were sufficiently downsized in two patients for hepatic resection and in one patient for radiofrequency ablation. Median Kaplan-Meier survival was 11.0 months (95 % confidence interval: 8.0-14.0 months) overall and 12.0 months in liver-only disease (±lung micro-nodules). Determinants of prolonged survival were response at 3 months (P = 0.046), ≤5 liver nodules (P = 0.004), single-liver-lobe involvement (P = 0.037), tumour-to-whole liver ratio <25 % (P = 0.021) and absence of extrahepatic metastases (P = 0.045). Adverse events possibly related to the nontarget distribution of (90)Y-RE were grade 1 (90)Y-RE-induced liver disease (n = 1), grade 2 and 3 gastric ulcers (n = 2). CONCLUSION: These results confirm the effectiveness and safety of selective (90)Y-RE in patients with chemotherapy-refractory mCRC, showing (90)Y-RE's potential as a bridging therapy to subsequent resection even in this end-stage population.

Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial.

PURPOSE: The aim of this retrospective two-centre study was to investigate the clinical impact of (11)C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer (rPCa) after radical therapy. METHODS: Enrolled in this retrospective study were 150 patients (95 from Bologna, 55 from Würzburg) with rPCa and biochemical relapse (PSA mean ± SD 4.3 ± 5.5 ng/mL, range 0.2-39.4 ng/mL) after radical therapy. The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative androgen deprivation therapy (ADT) in 55 patients. The effective clinical impact of (11)C-choline PET/CT was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. Multivariate binary logistic regression analysis included PSA level, PSA kinetics, ongoing ADT, Gleason score, TNM, age and time to relapse. RESULTS: Changes in therapy after (11)C-choline PET/CT were implemented in 70 of the 150 patients (46.7%). A major clinical impact was observed in 27 patients (18%) and a minor clinical impact in 43 (28.7%). (11)C-choline PET/CT was positive in 109 patients (72.7%) detecting local relapse (prostate bed and/or iliac lymph nodes and/or pararectal lymph nodes) in 64 patients (42.7%). Distant relapse (paraaortic and/or retroperitoneal lymph nodes and/or bone lesions) was seen in 31 patients (20.7%), and both local and distant relapse in 14 (9.3%). A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients (p < 0.05). In multivariate analysis, PSA level, PSA doubling time and ongoing ADT were significant predictors of a positive scan (p < 0.05). In statistical analysis no significant differences were observed between the Bologna and Würzburg patients (p > 0.05). In both centres the same criteria to validate PET-positive findings were used: in 17.3% of patients by histology and in 82.7% of patients by correlative imaging and/or clinical follow-up (follow-up mean 20.5 months, median 18.3 months, range 6.2-60 months). CONCLUSION: (11)C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients. It led to an overall change in 46.7% of patients, with a major clinical change implemented in 18% of patients. Further prospective studies are needed to evaluate the effect of such treatment changes on patient survival.

11C-choline PET/CT detects the site of relapse in the majority of prostate cancer patients showing biochemical recurrence after EBRT.

PURPOSE: The aim of this retrospective study was to evaluate the usefulness and the detection rate of (11)C-choline PET/CT in a population of patients with prostate cancer (PC), exclusively treated with external beam radiotherapy (EBRT) as primary treatment, who showed biochemical relapse. MATERIALS AND METHODS: We enrolled 140 patients showing a serum PSA level >2 ng/mL (mean 8.6 ng/mL, median 5 ng/mL, range 2 - 60 ng/mL). All patients had been treated with EBRT to the prostate gland and prostatic fossa with doses ranging from 70 to 76 Gy in low-risk patients (T1/T2 and/or serum PSA <10 ng/mL) and escalating to >76 Gy (range 76 - 81 Gy) in high-risk patients (T3/T4 and/or serum PSA >10 ng/mL). Of the 140 patients, 53 were receiving androgen deprivation therapy at the time of the scan. All positive (11)C-choline PET/CT findings were validated by transrectal ultrasound-guided biopsy or at least 12 months of follow-up with contrast-enhanced CT, MR, bone scintigraphy or a repeated (11)C-choline PET/CT scan. The relationships between the detection rate of (11)C-choline PET/CT and the factors PSA level, PSA kinetics, Gleason score, age, time to relapse and SUV max in patients with positive findings were analysed. RESULTS: (11)C-Choline PET/CT detected the site of relapse in 123 of the 140 patients with a detection rate of 87.8 % (46 patients showed local relapse, 31 showed local and distant relapse, and 46 showed only distant relapse). In patients with relapse the mean serum PSA level was 9.08 ng/mL (median 5.1 ng/mL, range 2 - 60 ng/mL), the mean PSA doubling time was 5.6 months (median 3.5 months, range 0.4 - 48 months), and the mean PSA velocity was 15 ng/mL/year (median 8.8 ng/mL/year, range 0.4 - 87 ng/mL/year). Of the 123 patients with relapse, 77 (62.6 %) showed distant relapse with/without local relapse, and of these 77, 31 (40.2 %) showed oligometastatic disease (one or two distant lesions: lymph node lesions only in 16, bone lesions only in 14, and lymph node lesions and bone lesions in 1). In univariate and multivariate analyses PSA kinetics was the only variable affecting (11)C-choline PET/CT detection rate. A significant correlation between PSA kinetics and site of recurrence (local relapse only vs. distant metastasis) was also observed. CONCLUSION: The detection rate of (11)C-choline PET/CT in patients with PC showing biochemical recurrence after EBRT as primary treatment is relatively high (87.8 %). (11)C-Choline PET/CT was able to detect extraprostatic disease in the 62.6 % of patients. Considering this high detection rate, (11)C-choline PET/CT could have clinical usefulness in the management of these PC patients, but this should be confirmed in future studies.

Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis.

Importance: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates. Objective: To assess the efficacy and tolerability of TNT protocols for LARC. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024. Study Selection: Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria. Data Extraction and Synthesis: Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach. Main Outcomes and Measures: The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival. Results: Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63). Conclusions and Relevance: In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.

SBRT in Lymph-Nodal Oligometastases from Prostate Cancer: Different Outcomes between Pelvic and Para-Aortic Disease.

Background: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph nodes; instead, para-aortic lymph nodes are considered as distant metastases. The aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Methods: This is a retrospective analysis. De novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; the pattern of recurrence was also evaluated. A propensity score matching (PSM) was applied to create comparable cohorts. The primary end-point was the progression-free survival (PFS). The secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS), and pattern of relapse. Results: In total, 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. The median PFS was 20 and 11 months in pelvic and para-aortic patients, respectively (p = 0.042). The difference was not confirmed in the multivariate analysis (p = 0.06). The median BRFS was 16 and 9 months, respectively, in the pelvic and para-aortic group (p = 0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-year LPFS was 90.5%. In PSM, no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have a PFS comparable to pelvic disease; local control is high in both cohorts. Our results also support the use of SBRT for para-aortic metastases.

Comparative Effectiveness of Chemotherapy Alone Versus Radiotherapy-Based Regimens in Locally Advanced Pancreatic Cancer: A Real-World Multicenter Analysis (PAULA-1).

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005-2018). Survival curves were calculated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34-0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13-0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28-0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22-0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

Treatment Planning in Intraoperative Radiation Therapy (IORT): Where Should We Go?

As opposed to external beam radiation therapy (EBRT), treatment planning systems (TPS) dedicated to intraoperative radiation therapy (IORT) were not subject to radical modifications in the last two decades. However, new treatment regimens such as ultrahigh dose rates and combination with multiple treatment modalities, as well as the prospected availability of dedicated in-room imaging, call for important new features in the next generation of treatment planning systems in IORT. Dosimetric accuracy should be guaranteed by means of advanced dose calculation algorithms, capable of modelling complex scattering phenomena and accounting for the non-tissue equivalent materials used to shape and compensate electron beams. Kilovoltage X-ray based IORT also presents special needs, including the correct description of extremely steep dose gradients and the accurate simulation of applicators. TPSs dedicated to IORT should also allow real-time imaging to be used for treatment adaptation at the time of irradiation. Other features implemented in TPSs should include deformable registration and capability of radiobiological planning, especially if unconventional irradiation schemes are used. Finally, patient safety requires that the multiple features be integrated in a comprehensive system in order to facilitate control of the whole process.

Breast conservative surgery and whole breast radiotherapy versus breast conservative surgery and IORT: surgical opinion.

BACKGROUND: To define the possibility of intraoperative radiation therapy (IORT)'s application on clinical practice and point out the problems observed by Verona Breast Unit. METHODS: Among the patients of the Breast Unit at Azienda Ospedaliera Universitaria Integrata of Verona, treated between July 2015 and June 2017, were identified 459 patients undergoing breast conserving surgery for a carcinoma, followed by IORT in 77 cases or by Whole Breast Radiotherapy (WBRT) in 382 cases. The data of WBRT group were analyzed considering IORT eligibility criteria to identify a sub-group of eligible patients, for whom we evaluated the diagnostic process that had led to exclusion from IORT. RESULTS: In WBRT group 184 patients (48%) had a ductal NOS infiltrating carcinoma, of which 64 cases (16.8%) were eligible for IORT. Other 79 patients of WBRT group (21%) presented DCIS, of which only 27 were in the American Society for Radiation Oncology "suitable" group for IORT. Considering the results of the preoperative exams, or rather needle biopsy and MRI scan, 55 patients of 64 (85.9%) resulted unsuitable for IORT, while nine patients (14.1%) could be eligible. CONCLUSIONS: IORT's major limits are: the restricted eligibility criteria, especially on histology; the need of a complete execution of preoperative exams and the technical limits of these exams. ASTRO suitable group, including small diameter, low-grade DCIS, might be used to extend the eligibility criteria. A multidisciplinary approach might improve the preoperative study, so the use of IORT in clinical practice.

Ablative Radiotherapy (ART) for Locally Advanced Pancreatic Cancer (LAPC): Toward a New Paradigm?

Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of intensive multi-agent chemotherapy regimens and aggressive surgical approaches, the survival of LAPC patients has significantly improved. In this complex and rapidly evolving scenario, the role of radiotherapy is still debated. The use of standard-dose conventional fractionated radiotherapy in LAPC has led to unsatisfactory oncological outcomes. However, technological advances in radiation therapy over recent years have definitively changed this paradigm. The use of ablative doses of radiotherapy, in association with image-guidance, respiratory organ-motion management, and adaptive protocols, has led to unprecedented results in terms of local control and survival. In this overview, principles, clinical applications, and current pitfalls of ablative radiotherapy (ART) as an emerging treatment option for LAPC are discussed.

Study Design and Rationale for Espera Trial: A Multicentre, Randomized, Phase II Clinical Trial Evaluating the Potential Efficacy of Adding SBRT to Pembrolizumab-Pemetrexed Maintenance in Responsive or Stable Advanced Non-Squamous NSCLC After Chemo-Immunotherapy Induction.

BACKGROUND: Improvement in radiotherapy techniques and expected outcomes, as well as in understanding the underlying biological mechanisms contributing to its action (immunomodulation in primis), led to the integration of this therapeutical approach in the current management of advanced non-small cell lung cancer (NSCLC), not only in oncogene-driven tumors, but also in non-oncogene addicted NSCLC where the combination of platinum-based chemotherapy plus pembrolizumab represents nowadays the pivotal strategy. In this light, we have designed a randomized phase II (ESPERa) trial to evaluate the efficacy and safety of adding Stereotactic Body Radiotherapy (SBRT) to pembrolizumab-pemetrexed maintenance in advanced NSCLC patients experiencing disease response or stability after chemo-immunotherapy induction. PATIENTS AND METHODS: Advanced non-oncogene addicted NSCLC patients with ECOG performance status of 0 or 1, who obtained disease response or stability after 4 cycles of platinum-based chemotherapy plus pembrolizumab will be randomized 2:1 to receive pembrolizumab-pemetrexed maintenance plus SBRT vs pembrolizumab-pemetrexed alone. The primary endpoint is progression-free survival (PFS). Concomitant translational researches will be performed to identify potential prognostic and/or predictive biomarkers, as well as to analyze and monitor tumour microenvironment and tumor-host interactions. CONCLUSIONS: Although available data suggest the safety and efficacy of combining immunotherapy and radiotherapy, their systematic integration in the current first-line landscape still remains to be explored. If the pre-planned endpoints of the ESPERa trial will be achieved, the addition of SBRT to pembrolizumab-pemetrexed maintenance as a strategy to consolidate and ideally improve the awaited benefit could be considered as a promising strategy in NSCLC undergoing first-line therapy, as well as an interesting approach to be evaluated in other disease setting, as well as in other oncological malignancies where immunotherapy represents nowadays the standard-of-care.

Integrating supportive care into the multidisciplinary management of lung cancer: we can't wait any longer.

INTRODUCTION: Due to important achievements in terms of diagnostic and therapeutic tools and the complexity of the disease itself, lung cancer management needs a multidisciplinary approach. To date, the classical multidisciplinary team involves different healthcare providers mainly dedicated to lung cancer diagnosis and treatments. Nevertheless, the underlying disease and related treatments significantly impact on patient function and psychological well-being. In this sense, supportive care may offer the best approach to relieve and manage patient symptoms and treatment-related adverse events. AREAS COVERED: Evidence reports that exercise, nutrition, smoking cessation, and psychological well-being bring many benefits in patients with lung cancer, from both a physical and socio-psychological points of view, and potentially improving their survival. Nevertheless, supportive care is rarely offered to patients, and even less frequently these needs are discussed within the multidisciplinary meeting. EXPERT OPINION: Integrating supportive care as part of the standard multidisciplinary approach for lung cancer involves a series of challenges, the first one represented by the daily necessity of specialists, such as kinesiologists, dietitians, psycho-oncologists, able to deliver a personalized approach. In the era of precision medicine, this is an essential step forward to guarantee comprehensive and patient-centered care for all patients with lung cancer.

Long-Term Outcomes Using Electron IOERT APBI for Early Stage Breast Cancer: The Verona University Hospital Experience.

METHODS AND MATERIALS: From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status. RESULTS: With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively. CONCLUSION: Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.

Computed tomography-based radiomic to predict resectability in locally advanced pancreatic cancer treated with chemotherapy and radiotherapy.

BACKGROUND: Surgical resection after neoadjuvant treatment is the main driver for improved survival in locally advanced pancreatic cancer (LAPC). However, the diagnostic performance of computed tomography (CT) imaging to evaluate the residual tumour burden at restaging after neoadjuvant therapy is low due to the difficulty in distinguishing neoplastic tissue from fibrous scar or inflammation. In this context, radiomics has gained popularity over conventional imaging as a complementary clinical tool capable of providing additional, unprecedented information regarding the intratumor heterogeneity and the residual neoplastic tissue, potentially serving in the therapeutic decision-making process. AIM: To assess the capability of radiomic features to predict surgical resection in LAPC treated with neoadjuvant chemotherapy and radiotherapy. METHODS: Patients with LAPC treated with intensive chemotherapy followed by ablative radiation therapy were retrospectively reviewed. One thousand six hundred and fifty-five radiomic features were extracted from planning CT inside the gross tumour volume. Both extracted features and clinical data contribute to create and validate the predictive model of resectability status. Patients were repeatedly divided into training and validation sets. The discriminating performance of each model, obtained applying a LASSO regression analysis, was assessed with the area under the receiver operating characteristic curve (AUC). The validated model was applied to the entire dataset to obtain the most significant features. RESULTS: Seventy-one patients were included in the analysis. Median age was 65 years and 57.8% of patients were male. All patients underwent induction chemotherapy followed by ablative radiotherapy, and 19 (26.8%) ultimately received surgical resection. After the first step of variable selections, a predictive model of resectability was developed with a median AUC for training and validation sets of 0.862 (95%CI: 0.792-0.921) and 0.853 (95%CI: 0.706-0.960), respectively. The validated model was applied to the entire dataset and 4 features were selected to build the model with predictive performance as measured using AUC of 0.944 (95%CI: 0.892-0.996). CONCLUSION: The present radiomic model could help predict resectability in LAPC after neoadjuvant chemotherapy and radiotherapy, potentially integrating clinical and morphological parameters in predicting surgical resection.

Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study.

BACKGROUND: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. OBJECTIVE: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. INTERVENTION: The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. RESULTS AND LIMITATIONS: Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9-7.1) and median OS 20 mo (95% CI, 17-not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. CONCLUSIONS: We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. PATIENT SUMMARY: Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

Risk Adapted Ablative Radiotherapy After Intensive Chemotherapy for Locally Advanced Pancreatic Cancer.

BACKGROUND AND OBJECTIVE: To assess the efficacy of a Risk-Adapted Ablative Radiotherapy (RAdAR) approach, after intensive induction chemotherapy, in patients with locally advanced pancreatic cancer (LAPC). MATERIAL AND METHODS: Patients with LAPC who received RAdAR following induction chemotherapy from January 2017 to December 2019 were included in this observational study. The RAdAR approach consisted of an anatomy- and simultaneous integrated boost (SIB)-based dose prescription strategy. RAdAR was delivered with stereotactic ablative radiation therapy (SAbR), administering 30 Gy in 5 fractions to the tumor volume (PTVt) and 50 Gy SIB (BED10 100 Gy) to the vascular involvement, or with (hypo-)fractionated ablative radiotherapy (HART) prescribing 50.4 Gy in 28 fractions to the PTVt, with a vascular SIB of 78.4 Gy (BED10 100 Gy). Primary end points were freedom from local progression (FFLP), overall survival (OS), and progression-free survival (PFS). RESULTS: Sixty-four LAPC patients were included. Induction chemotherapy consisted of gemcitabine/nab-paclitaxel in 60.9% and FOLFIRINOX in 39.1% of cases. SAbR was used in 52 (81.2%) patients, and HART in 12 (18.8%). After RAdAR, surgery was performed in 17 (26.6%) patients. Median follow-up was 16.1 months. Overall local control (LC) rate was 78.1%, with no difference between resected and non-resected patients (2-year FFLP 75.3% vs 56.4%; p = 0.112). Median OS and PFS were 29.7 months and 8.7 months, respectively, for the entire cohort. Resected patients had a better median OS (not reached versus 26.1 months; p = 0.0001) and PFS (19 versus 5.6 months; p < 0.0001) compared to non-resected patients. In non-resected patients, no significant difference was found between SAbR and HART for median FFLP (28.1 versus 18.5 months; p = 0.614), OS (27.4 versus 25.3 months; p = 0.624), and PFS (5.7 versus 4.3 months; p = 0.486). One patient (1.6%) experienced acute grade 4 gastro-intestinal bleeding. No other acute or late grade ≥ 3 toxicities were observed. CONCLUSIONS: The RAdAR approach, following intensive induction chemotherapy, is an effective radiation treatment strategy for selected LAPC patients, representing a promising therapeutic option in a multimodality treatment regimen.

Melanoma of Unknown Primary: Evaluation of the Characteristics, Treatment Strategies, Prognostic Factors in a Monocentric Retrospective Study.

BACKGROUND: Melanoma of unknown primary (MUP), accounts for up to 3% of all melanomas and consists of a histologically confirmed melanoma metastasis to either lymph nodes, (sub)cutaneous tissue, or visceral sites without any evidence of a primary cutaneous, ocular, or mucosal melanoma. This study aimed to investigate the characteristics, treatment strategies, and prognostic factors of MUP patients, in order to shed some light on the clinical behavior of this malignancy. METHODS: All the consecutive patients with a diagnosis of MUP referring to our institutions between 1985 and 2018 were considered in this retrospective cohort study. The records of 173 patients with a suspected diagnosis of MUP were retrospectively evaluated for inclusion in the study. Patient selection was performed according to the Das Gupta criteria, and a total of 127 MUP patients were finally included in the study, representing 2.7% of the patients diagnosed with melanoma skin cancer at our institutions during the same study period. A second cohort of all consecutive 417 MKP patients with AJCC stages IIIB-IV, referring tions in the period considered (1985-2018), was included in the study to compare survival between MUP and MKP patients. All the diagnoses were based on histopathologic, cytologic and immunohistochemical examination of the metastases. All tumors were re-staged according to the 2018 American Joint Committee on Cancer (AJCC) 8th Edition. RESULTS: Median follow-up was 32 months (IQR: 15-84). 3-year progression-free survival (PFS) was 54%, while 3-year overall survival (OS) was 62%. Worse OS and PFS were associated with older age (P = 0.0001 for OS; P = 0.008 for PFS), stage IV (P < 0.0001 for OS; P = 0.0001 for PFS) and higher Charlson Comorbidity Index (P < 0.0001 for OS and P = 0.01 for PFS). Patients with lymph node disease showed longer PFS (P = 0.001) and OS (P = 0.0008) than those with (sub)cutis disease. Complete lymph node dissection (CLND) was the most common surgical treatment; a worse OS in these patients was associated with the number of positive lymph nodes (P = 0.01), without significant association with the number of retrieved lymph nodes (P = 0.79). Survival rates were lower in patients undergoing chemotherapy (CT) and target therapy (TT), and higher in those receiving immunotherapy (IT). 417 patients with AJCC stages IIIB-IV of Melanoma Known Primary (MKP) were included for the survival comparison with MUP. 3-year PFS rates were 54 and 58% in MUP and MKP, respectively (P = 0.30); 3-year OS rates were 62 and 70% in MUP and MKP, respectively (P = 0.40). CONCLUSIONS: The most common clinical scenario of our series was a male patient around 59 years with lymph node disease. We report that CLND associated with IT was the best treatment in terms of survival outcome. In the current era of IT and TT for melanoma, new studies have to clarify the impact of novel drugs on MUP.