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Purpose: Boron Neutron Capture Therapy (BNCT) represents an advanced radiation therapy capable of selectively killing tumor cells. It operates on a dual therapy approach, utilizing boronated agents that preferentially deliver boron-10 to tumors, followed by neutron irradiation. This leads to the emission of two ionizing particles. These particles expend all their energy over a distance comparable to the diameter of a cell and can cause irreparable damage to DNA when passing through the nucleus. Methods: This paper outlines the approach taken by the Italian National Cancer Center for Oncological Hadrontherapy (CNAO) to achieve BNCT certification for clinical applications within the EU regulatory framework. Results: The existing literature reports excellent outcomes for many unresectable and recurrent tumors, especially in head and neck cancer (HNC). Conclusions: The paper seeks to clarify the rationale and methods for formulating a clinical trial design to meet these objectives. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with unresectable ovarian cancer during cytoreductive surgery for advanced-stage ovarian cancer are typically underreported. Hence, knowledge of further postoperative treatment and survival in case of unresectable disease during surgery is limited. The aim of this study is to address the knowledge gap about postoperative treatment and survival of patients whose surgery was abandoned due to unresectability after abdominal exploration. This is a post hoc analysis of the PlaComOv study, a randomized controlled trial. In this prospective study, 27 patients with the unresectable disease are described. Treatment was divers, ranging from the cessation of treatment to, predominantly, one or several lines of chemotherapy with or without maintenance treatment with bevacizumab and/or PARP inhibitors. The median overall survival after surgery was 16 (IQR 5–21) months (95%CI 14–18). At 24 months of follow-up, four patients (15%) were alive with the disease. Background: Patients with unresectable disease during cytoreductive surgery (CRS) for advanced-stage ovarian cancer are underreported. Knowledge of treatment and survival after surgery is limited. The aim of this study is to address the knowledge gap about postoperative treatment and survival of patients whose surgery was abandoned due to unresectability after abdominal exploration. Methods: Women with FIGO stage IIIB-IV epithelial ovarian cancer whose disease was considered to be unresectable during surgery were included in this prospective study, a post hoc analysis of the PlaComOv study. The unresectable disease was defined as the inability to achieve at least suboptimal CRS without attempted CRS after careful inspection of the entire abdomen. Preoperative clinical data, perioperative findings, postoperative treatment and survival data were analyzed. Results: From 2018 to 2020, 27 patients were included in this analysis. Treatment ranged from the cessation of treatment to one or several lines of chemotherapy with or without maintenance therapy. The median overall survival was 16 (IQR 5–21) months (95%CI 14–18). At 24 months of follow-up, four patients (15%) were alive. Conclusions: This study indicated a two-year survival of 15%. Optimal treatment strategies in terms of survival benefits are still ill-defined. Further study of this specific group of patients is warranted. We advocate an (inter)national registry of patients with unresectable cancer and comprehensive follow-up. [ABSTRACT FROM AUTHOR]

Study Design: This was a subanalysis of an international, multicenter, open-label study.Objective: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992).Summary Of Background Data: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine).Methods: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3).Results: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts).Conclusion: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Aim: We aimed at determining the prognostic value of the albumin-bilirubin grade (ALBI) in patients undergoing transarterial Chemoembolization for unresectable Hepatocellular carcinoma. Background: Various noninvasive liver reserve markers are used to predict the severity of liver injury. The role and probability of these markers in predicting the prognosis of patients with hepatocellular carcinoma (HCC) is still unknown. Methods: Patients who underwent TACE from 2013 to 2017 were included. Patient's age, gender, cause of cirrhosis, ALBI Grade along with the site, size and number of tumors were recorded. Radiological response to TACE was assessed by CT scan at 1 and 3 months after the procedure, respectively. Survival assessment was performed and all patients were assessed for survival until the last follow-up. Results: A total of 71 patients were included. Majority of them were male (80.3 %). The mean tumor size of 6 ± 3.9 cm. Majority of patients (54.9 %) had a single lesion and it was mostly localized to the right lobe (60.5 %). The most common cause of chronic liver disease was HCV (65.3%). Median Child class score (CTP) and MELD score were 7 and 10, respectively. Ascites was treated prior to TACE in 12 patients (16.9 %). Mean ALBI score in the study population was -1.59 ± 0.69, with the majority (49. 2 %) falling in grade 2. The mean duration of survival at the last follow up was of 12.1 ± 12.14 months (1- 49). Univariate analysis showed serum albumin (p = 0.003), serum bilirubin (p = 0.018), CTP score (p = 0.019), ALBI grade (p = 0.001) and presence of varices (p = 0.04) to be the main predictors of 6 months survival after TACE. On Cox analysis, only ALBI score (p = 0.038) showed statistical significant association. Conclusion: ALBI grade may serve as a surrogate marker in predicting the prognosis of HCC patients undergoing Transarterial Chemoembolization. [ABSTRACT FROM AUTHOR]

Background: The prognosis of locally unresectable colon cancer (CC) is poor. This prospective observational study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery in these patients. Patients and methods: We consecutively enrolled patients who were diagnosed with locally unresectable CC from November 2010 to March 2017, and received NACRT followed by surgery. The data of all the patients were collected prospectively. The R0 resection, downstage and pathologic complete response (pCR) rates were calculated to evaluate the short-term treatment effects. The overall survival (OS) was used to evaluate the long-term outcome. The incidence of NACRT-related acute toxicities and postsurgical complications were used to assess the safety. Results: A total of 60 patients were eligible for analysis, including 57 (95.0%) patients who attained resectability after NACRT. Among patients managed with surgery, 49 cases (86.0%) achieved R0 resection, and 15 cases (26.3%) achieved pCR. Down T stage was seen in 47 cases (82.5%), and down N stage was seen in 53 cases (93.0%). After a median follow-up time of 26 months, the OS appeared as 76.7%. The most common grade 3/4 NACRT-related toxicity was myelosuppression (incidence, 20.0%). The incidence of grade 3/4 surgery-related complication was 7.0%. Conclusion: NACRT might be a safe and effective choice for patients with locally unresectable CC to improve treatment effects, long-term survival and life quality, though further validation is needed. [ABSTRACT FROM AUTHOR]

Objective: To determine oncological and neuromorbidity outcomes in patients with advanced head and neck cancer (stage IVB) requiring sacrifice and reconstruction of the carotid artery. Study Design: Case series with chart review. Setting: Tertiary care referral center. Subjects and Methods: Overall, 51 patients underwent carotid artery sacrifice during surgical treatment of the neck, in both the primary and salvage setting. All patients underwent autogenous in-line carotid artery bypass grafting with either saphenous vein or the deep femoral vein in conjunction with vascular surgery. In all, the study included 39 males and 12 female subjects, with age ranging from 39 to 82 (mean, 62.7). Results: Two patients (3.9%) had a cerebral vascular accident in the immediate postoperative period. The remaining 49 patients (96%) had no neurologic sequela. Serial ultrasonic evaluation revealed 4 patients with intra-luminal thrombus within the site of reconstruction. Perioperative mortality occurred in a single patient. Disease-related mortality occurred in 9.8% (5) of patients, with an overall 2-year survival of 82%. Conclusions: We presently report the largest series of surgical treatment for advanced head and neck cancer with carotid artery involvement. We document an overall 2-year survival of 82% in the setting of low perioperative neuromorbidity and mortality rates. We therefore consider carotid artery sacrifice and autogenous vein graft reconstruction in the absence of distant metastatic disease as a viable treatment option for what was once thought to be a palliative procedure. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Hypofractionated radiotherapy (RT) of pancreatic adenocarcinoma is limited by the tolerance of adjacent normal tissues. A better understanding of the influence of dosimetric variables on the rate of toxicity after RT must be considered an important goal. Methods and materials: Sixty-one patients with histologically proven locally advanced disease (LAPD) were analyzed. The therapeutic strategy consisted of induction chemotherapy (ChT) followed by concurrent chemoradiotherapy (CRT). In 39 out of 61 patients the target volume was based on a four-dimensional CT (4D-CT) procedure. Delivered dose was 44.25Gy in 15 fractions to PTV2, which consisted of pancreatic tumor and regional lymph nodes considered radiologically involved; 23 out of 61 patients received a simultaneous integrated boost (SIB) to a tumor sub-volume infiltrating the great abdominal vessels (PTV1) with dose in the range of 48–58Gy. RT was delivered with Helical Tomotherapy. Dose–volume histograms (DVHs) of target volumes and organs at risk (OARs) were collected for analysis. The predictive value of clinical/dosimetric parameters was tested by univariate/multivariate analyses. Results: The crude incidence of acute gastrointestinal (GI) grade 2 toxicity was 33%. The 12-month actuarial rate of “anatomical” (gastro-duodenal mucosa damage) toxicity was 13% (95% CI: 4–22%). On univariate analysis, several stomach and duodenum DVH endpoints are predictive of toxicity after moderately hypofractionated radiotherapy. Multivariate analysis confirmed that baseline performance status and the stomach V 20[%] were strong independent predictors of acute GI grade ⩾2 toxicity. The high-dose region of duodenum DVH (V 45[%]; V 40[%]) was strongly correlated with grade ⩾2 “anatomical” toxicity; the best V 40[%] and V 45[%] cut-off values were 16% and 2.6% respectively. Conclusion: Regarding dosimetric indices, stomach V 20[%] correlates with a higher rate of acute toxicity; more severe acute and late anatomical toxicities are related to the high dose region of duodenum DVH. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the predictive value of conventional criteria for identifying surgically unresectable disease among patients with ovarian cancer undergoing initial operative intervention at tertiary referral centers employing a so-called aggressive approach to surgical cytoreduction. Methods: All patients with advanced epithelial ovarian cancer undergoing primary surgery between August 1997 and August 2006 were identified. Surgical/pathological documentation of disease extent pre/post-cytoreduction was extracted from the medical record retrospectively. All patients meeting conventional criteria for unresectable disease criteria (ascites>1000 mL, omental extension to spleen >1 cm, parenchymal liver disease >1cm, porta hepatis involvement >1 cm, diaphragmatic disease >1 cm, carcinomatosis >1 cm, and suprarenal adenopathy >1 cm) were selected for further study. Results: A total of 180 consecutive patients had disease meeting conventional criteria for unresectability at =1 site(s). Optimal cytoreduction (residual disease =1 cm) was achieved in 166 patients (92.2%). Optimal resection rates according to the most common individual unresectable disease criteria were as follows: ascites >1000 mL=91.3% (116/127), carcinomatosis >1 cm=91.0% (81/89), and splenic involvement >1 cm=84.9% (45/53). For patients with ascites >1000 mL alone, optimal cytoreduction was achieved in 95.8% (46/48) of cases. Optimal resection rates according to the total number of unresectable disease sites were as follows: 1 site=95.0% (19/20), 2 sites=93.8% (61/65), 3 sites=81.5% (22/27), 4 sites=93.3% (14/15), and 5 sites=80.0% (4/5). Conclusions: These data suggest that commonly accepted criteria of surgically unresectable disease for women with advanced ovarian cancer lack the necessary precision to guide clinical management. Pre-operative assessment of resectability should be made by an experienced surgical team prior to deferring the initial attempt at surgical cytoreduction. [Copyright &y& Elsevier]