Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine.

This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of 'all-comer' treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality.

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.

Somatostatin receptor positron emission tomography/computed tomography imaging in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous carcinoma with neuroendocrine differentiation. However, literature data about the use of somatostatin receptor positron emission tomography/computed tomography (PET/CT) imaging in MCC are limited and its role is not clearly stated. OBJECTIVE: To investigate the role of PET/CT using somatostatin analogues radiolabelled with gallium-68 in patients with MCC. METHODS: All patients affected by MCC who performed a somatostatin receptor PET/CT imaging from October 2007 to May 2014 were retrospectively analysed. The diagnostic performances of PET/CT were evaluated on a patient-based analysis and compared to final diagnosis (histology = 3 or clinical/radiological follow-up = 20). RESULTS: We evaluated 23 consecutive MCC patients [18 men; median age 71 years (range 47-87)]. Primary tumour was located in ear (1/23), cheek (3/23), arm (2/23), hand (1/23), back (1/23), anal canal (1/23), gluteus (4/23), thigh (3/23) and popliteal fossa (1/23). In 6/23 patients, the site of primary tumour was unknown. PET/CT was performed to detect primary tumour site (4/23) or to stage (8/23) or re-stage (11/23) patients. PET/CT resulted positive in 14/23 patients and according to the final diagnosis was defined true positive, true negative, false positive (FP) and false negative in 11/23, 8/23, 3/23 and 1/23 cases respectively. FP PET/CT results were due to unspecific liver uptake, post-surgical inflammation and pancreatic neuroendocrine tumour. PET/CT was unable to detect primary tumour site in all patients with unknown primary MCC. Sensitivity, specificity and diagnostic accuracy of PET/CT were 92%, 73% and 83% respectively. CONCLUSIONS: In our experience, somatostatin receptor PET/CT imaging resulted useful in patients with MCC and presented high diagnostic performances with a significant impact in disease management although in patients with unknown primary MCC, it was unable to identify the primary tumour site.

A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study.

BACKGROUND: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. PATIENTS AND METHODS: Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. RESULTS: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). CONCLUSIONS: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. CLINICAL TRIAL NUMBER: NCT00753675.

Limbic system mGluR5 availability in cocaine dependent subjects: a high-resolution PET [(11)C]ABP688 study.

Cocaine self-administration decreases type 5 metabotropic glutamate receptor (mGluR5) tissue concentrations in laboratory rats during early abstinence. These changes are thought to influence the drug's reinforcing properties and the ability of drug-related cues to induce relapse. Here, our goal was to measure brain regional mGluR5 availability in recently abstinent cocaine dependent humans. Participants meeting DSM-IV diagnostic criteria for current cocaine dependence (n=9) were recruited from the general population. mGluR5 availability (binding potential, non-displaceable; BPND) was measured with high-resolution positron emission tomography (PET HRRT) and [(11)C]ABP688. Compared to age- and sex-matched healthy controls (n=9), cocaine dependent subjects showed significantly lower BPND values in the ventral (bilateral: -28.2%, p=0.011), associative (right: -21.4%, p=0.043), and sensorimotor striatum (bilateral: -21.7%, p=0.045), amygdala (left: -26%, p=0.046) and insula (right: -23.3%, p=0.041). Among the cocaine users, receptor availabilities were related to abstinence (range: 2 to 14days). The longer the duration of abstinence, the lower the BPND values in the sensorimotor striatum (r=-0.71, p=0.034), left amygdala (r=-0.73, p=0.026) and right insula (r=-0.67, p=0.046). Compared to healthy controls, BPND values were significantly reduced in those who tested negative for cocaine on the PET test session in the ventral (p=0.018) and sensorimotor striatum (p=0.017), left amygdala (p=0.008), and right insula (p=0.029), but not in those who tested positive. Together, these results provide evidence of time-related mGluR5 alterations in striatal and limbic regions in humans during early cocaine abstinence.

Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer.

BACKGROUND: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. METHODS: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. RESULTS: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001). CONCLUSIONS: Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.

A cross-sectional study evaluating the exercise discussion with oncologist during cancer consultation: the CONNECT study.

BACKGROUND: Evidence demonstrates that physical exercise confers several psycho-physical benefits on patients with cancer. This study aims to investigate the role of oncologists in exercise promotion. PATIENTS AND METHODS: A multicenter, cross-sectional study was conducted by distributing an anonymous, self-administered questionnaire to patients with cancer. The questionnaire enclosed demographic, health, and exercise variables. The exercise-related questions included in the study used the Godin-Shephard Leisure-Time Physical Activity Questionnaire to measure the amount of physical exercise. In addition, the survey gathered information on whether exercise was discussed with patients, and whether oncologists followed the assess, advise, reinforce, and refer (AARR) process regarding exercise. The survey also asked if patients preferred that exercise be discussed during their consultations. Descriptive statistics and logistic regression were applied. RESULTS: With a response rate of 75%, a total of 549 patients completed the survey. Regarding the exercise discussion, 38% of patients stated that their oncologist initiated an exercise discussion, 14% started the discussion themselves, and 48% said that the issue was not considered. Overall, 35% of patients reported that the oncologist assessed their exercise level, 22% and 42% received advice or reinforcement to increase their exercise, respectively, and 10% were referred to a dedicated service. Regarding preferences, 72% of patients thought that the oncologists should initiate an exercise discussion, 2% that only patients should start the discussion, and 26% thought that the issue should not be discussed. Similarly, 74% of patients are willing to receive the exercise assessment, 59% and 75% the advice and reinforcement to increase their exercise, and 46% to be referred to an exercise service. CONCLUSIONS: Although exercise promotion rates are low, patients are willing to receive exercise information. Dedicated strategies should be developed to support oncologists in promoting exercise to their patients.

Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey.

BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role?

This study was conducted to determine whether the adding thymosin alpha-1 to standard of care for re-treatment of nonresponding hepatitis C infections can improve sustained viral response (SVR) rates. Patients (n = 552) with hepatitis C infections not responding to the combination of Peginterferon alfa-2a or 2b with ribavirin (RBV)were randomized to receive peginterferon alfa-2a 180 mg/week with RBV 800-1200 mg/daily plus either thymosin alpha-1 1.6 mg SC twice weekly (n = 275) or placebo (n = 277) for 48 weeks. Eighty-eight per cent of patients had HCV genotype 1, 6.6% type 4, 2.2% type 2 and 3.6% type 3. SVR rates in the intention to treat population were similar between thymosin alpha-1 and placebo (12.7%vs 10.5%; P = 0.407). Among patients who completed all 48 weeks of therapy, the SVR rate was significantly higher in the thymosin alpha-1 group at 41.0% (34/83) compared with 26.3% (26/99) in the placebo group (P = 0.048). No significant difference was observed between treatment groups in the incidence of adverse events. The addition of thymosin alpha-1 to the standard of care did not increase the on-treatment HCV viral response. Thymosin alpha-1 seems to play no role in the primary therapy of the disease. This study raises the hypothesis that thymosin alpha-1 may have a secondary therapeutic role as an adjuvant in the prevention of relapses in patients achieving a virologic response during therapy.

SCCA-IC serum levels are predictive of clinical response in HCV chronic hepatitis to antiviral therapy: a multicentric prospective study.

The combination of pegylated interferon (Peg-IFN) and ribavirin is currently the gold standard therapy in patients with HCV chronic infection. The duration of therapy, as well as the therapeutic dosage, depend on the genotype. Identification of the genotype and rapid virological response (RVR) are widely accepted as the most important predictors of clinical outcome during antiviral therapy but to optimize cost-benefits and to reduce possible side effects, further prognostic factors are needed. Squamous cell carcinoma antigens immunocomplex (SCCA-IC) has been reported to be increased in the serum of patients with liver cancer. In this multicentric prospective study, we investigated the serum levels of SCCA-IC in 103 patients with HCV chronic infection. Serum HCV-RNA was detected before the beginning of treatment, after 4, 12, 24 or 48 weeks, and at week 24 during follow-up. RVR, early virological response and sustained virological response (SVR) were assessed following the international guidelines. SCCA-IC levels were higher in responders (238 AU, interquartile difference 130-556 AU) and decreased significantly to 125 AU (70-290 AU). The mean baseline value in nonresponders was 149 AU (86.5-306.5 AU), but after 4 weeks of treatment the serum levels decreased to 115 AU (80-280 AU): the profile of reduction was different between patients with or without a positive SVR. Logistic regression with SVR as dependent variable identified as significant independent variables: the reduction in SCCA-IC after 1 month (OR = 4.82; 95% CI 1.39-16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21-0.42; P = 0.002); sex and age were also significant factors influencing SVR. SCCA-IC seems to be a reliable independent prognostic marker of therapeutic effectiveness in anti-HCV positive patients undergoing antiviral therapy.

Colorectal retained foreign bodies per anum introduced. Three years retrospective study at Emergency Surgery Unit.

Colorectal foreign bodies per annum introduced are not exceptional. They can be classified as high-lying or low-lying, depending on their location relative to the recto-sigmoid junction. High-lying rectal foreign bodies sometimes require surgery; low-lying ones are often palpable by digital examination and can removed at bedside. No reliable data exist regarding the frequency of inserted rectal foreign bodies and the literature is largely anecdotal. We review our experience on patients almost all males and heterosexual with retained colorectal foreign bodies and their outcome in Surgical Emergency Unit of a Southern Italy University hospital.

New insights on commemoration of the dead through mortuary and architectural use of pigments at Neolithic Çatalhöyük, Turkey.

The cultural use of pigments in human societies is associated with ritual activities and the creation of social memory. Neolithic Çatalhöyük (Turkey, 7100-5950 cal BC) provides a unique case study for the exploration of links between pigments in burials, demographic data and colourants in contemporary architectural contexts. This study presents the first combined analysis of funerary and architectural evidence of pigment use in Neolithic Anatolia and discusses the possible social processes underlying the observed statistical patterns. Results reveal that pigments were either applied directly to the deceased or included in the grave as a burial association. The most commonly used pigment was red ochre. Cinnabar was mainly applied to males and blue/green pigment was associated with females. A correlation was found between the number of buried individuals and the number of painted layers in the buildings. Mortuary practices seem to have followed specific selection processes independent of sex and age-at-death of the deceased. This study offers new insights about the social factors involved in pigment use in this community, and contributes to the interpretation of funerary practices in Neolithic Anatolia. Specifically, it suggests that visual expression, ritual performance and symbolic associations were elements of shared long-term socio-cultural practices.

Integrative molecular analysis of combined small-cell lung carcinomas identifies major subtypes with different therapeutic opportunities.

BACKGROUND: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. MATERIALS AND METHODS: Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. RESULTS: All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. CONCLUSIONS: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).

Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+). PATIENTS AND METHODS: We conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design. RESULTS: Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36-0.58, P < 0.0001] and overall response rate (ORR) (HR 2.08, 95% CI 1.75-2.46, P < 0.0001)] over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials. CONCLUSIONS: In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ~25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation.

E-learning course improves knowledge in tobacco dependence, electronic nicotine delivery systems and heat-not-burn products in Medical School students.

BACKGROUND: Adequate training in tobacco, nicotine dependence and treatment is lacking in Medical School education. With the rise in popularity of electronic alternatives to cigarettes, future physicians should also be provided with the more recent scientific evidence on these products during their undergraduate studies. We introduced an e-learning course for Medical School students and assessed its effec-tiveness of increasing knowledge on these topics. METHODS: We developed 16 didactic modules divided in 3 courses: tobacco dependence (TDI), treating tobacco dependence (TDII) and electronic products and tobacco control (TDIII). The course was offered to 4th, 5th, and 6th year Medical School students in Italy. To assess learning outcomes, we examined the pre- to post- changes in knowledge scores associated with each course. Paired and independent samples t-tests were performed overall, and among smokers and non-smokers separately. RESULTS: A total of 1318 students completed at least one of the courses; 21% were self-reported smokers. A significant increase in knowledge was observed at the end of TDI (pre-course: 52.1±15.9, post-course: 79.9±13.5, p<0.001), TDII (pre-course: 52.5±13.0, post-course: 66.5±12.0, p<0.001) and TDIII (pre-course: 52.2±15.3, post-course: 76.1±17.7, p<0.001). Smokers showed significantly lower improvements compared to non-smokers. CONCLUSIONS: The e-learning course was effective in increasing knowledge about tobacco dependence, treatments, and electronic ni-cotine products in advanced medical students. Given the fundamental role for healthcare practitioners in encouraging and assisting people in quitting smoking, e-learning may be a useful tool in providing up-to-date and standardized training in the area during Medical School.

Thyroid disrupting effects of low-dose dibenzothiophene and cadmium in single or concurrent exposure: New evidence from a translational zebrafish model.

Thyroid hormones (THs) are major regulators of biological processes essential for correct development and energy homeostasis. Although thyroid disruptors can deeply affect human health, the impact of exogenous chemicals and in particular mixture of chemicals on different aspects of thyroid development and metabolism is not yet fully understood. In this study we have used the highly versatile zebrafish model to assess the thyroid axis disrupting effects of cadmium (Cd) and dibenzothiophene (DBT), two environmental endocrine disruptors found to be significantly correlated in epidemiological co-exposure studies. Zebrafish embryos (5hpf) were exposed to low concentrations of Cd (from 0.05 to 2 µM) and DBT (from 0.05 to 1 µM) and to mixtures of them. A multilevel assessment of the pollutant effects has been obtained by combining in vivo morphological analyses allowed by the use of transgenic fluorescent lines with liquid chromatography mass spectrometry determination of TH levels and quantification of the expression levels of key genes involved in the Hypothalamic-Pituitary-Thyroid Axis (HPTA) and TH metabolism. Our results underscore for the first time an important synergistic toxic effect of these pollutants on embryonic development and thyroid morphology highlighting differences in the mechanisms through which they can adversely impact on multiple physiological processes of the HPTA and TH disposal influencing also heart geometry and function.

Hypofractionated Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost and Simultaneous Integrated Protection in Pancreatic Ductal Adenocarcinoma.

AIMS: To evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: Patients receiving SBRT following induction chemotherapy from January 2017 to December 2018 were included in this observational analysis. SBRT was delivered in five consecutive daily fractions by administering 30 Gy to the planning target volume while simultaneously delivering a 50 Gy SIB to the tumour-vessel interface. SIP was created by lowering the dose to 25 Gy on the overlap area between the planning target volume and the planning organ at risk volume. The primary end point was acute and late gastrointestinal grade ≥3 toxicity. Secondary end points were freedom from local progression, overall survival and progression-free survival (PFS). RESULTS: Fifty-nine consecutive patients (27 borderline resectable and 32 locally advanced) were included. Fifty-eight patients (98.3%) completed the SBRT planned treatment and 35 patients (59.4%) received surgical resection following SBRT. No acute or late grade ≥3 SBRT-related adverse events were observed. The median follow-up time was 15.1 months in the overall cohort and 18.1 months in censored patients. One- and 2-year freedom from local progression rates were 85% and 80% versus 79.7% and 60.6% in resected and unresected patients, respectively (P = 0.33). The median overall survival and PFS were 30.2 months and 19 months from diagnosis and 19.1 months and 10.7 months from SBRT in the entire cohort. Resected patients had improved 2-year overall survival rates (72.5% versus 49%, P = 0.012) and median PFS (13 months versus 5 months; P < 0.001) relative to unresected patients. There was no survival difference between borderline resectable and locally advanced patients. CONCLUSIONS: SBRT with SIB/SIP had an excellent toxicity profile and could be administered safely on pancreatic ductal adenocarcinoma patients, even in a total neoadjuvant setting.