Background/Objectives: Early progression (EP) occurs in a subset of patients with locally advanced pancreatic cancer (LAPC), limiting the clinical benefit of treatment, and it remains difficult to predict. Methods: We developed a multiparametric predictive model integrating baseline 18F-FDG PET/CT radiomic features with clinical and biological data. A total of 242 radiomic features were extracted from each imaging modality (CT and PET), including first-order, gray-level co-occurrence matrix (GLCM), and local binary pattern (LBP-TOP) features, and combined with PET-derived metrics and clinical variables. Model development included cross-validation procedures and rigorous feature selection, followed by the training of a two-level decision tree classifier. Results: The model achieved an accuracy of 80.7% and an area under the curve (AUC) of 0.83. Integrated analysis of CT and PET texture enabled the identification of patients at high risk of EP prior to treatment initiation. Conclusions: PET/CT-based radiomic biomarkers, combined with clinical data, can non-invasively capture tumor heterogeneity and improve risk stratification in LAPC, supporting more personalized therapeutic decision-making.

AIM:The aim was to investigate the use of comprehensive pretreatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18F-FDG-positron emission tomography (PET)/computed tomography (CT) scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. MATERIALS AND METHODS:This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in CRT combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control, and metastasis-free survival. RESULTS:Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared tonon-resected patients (median PFS, 22.5 months vs. 9.5 months, P <0.001; median OS, 38.2 months vs. 13 months, P <0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to the upfront CRT group (median PFS, 19 months vs. 9.9 months, P <0.001; median OS, 19.3 months vs. 14.6 months, P <0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI: 0.12-1.02, P =0.05), and this data was confirmed at multivariate analysis (95% CI: 0.09-0.98, P =0.04). Hematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. CONCLUSIONS:The use of comprehensive pretreatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

Background: Pancreatic cancer, with its poor prognosis, is frequently diagnosed in elderly patients who may be ineligible for surgery or chemoradiation due to age or comorbidities. Stereotactic body radiotherapy (SBRT) offers a targeted approach by delivering precise, high-dose radiation to a limited volume in few fractions. This study aims to evaluate the efficacy and safety of SBRT in elderly pancreatic cancer patients. Methods: Patients with pancreatic cancer received SBRT using Volumetric Modulated Arc Therapy in schedules of five dose fractions tailored to the tolerance of adjacent tissues. Progression-free survival (PFS), local progression-free survival (LPFS), metastasis-free survival (MFS) and overall survival (OS) were analysed. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 9.5 months (range, 4-37.2 months). The 1-year, 2-year and 3-year LPFS rates were 88%, 73% and 54%, respectively (median not reached). Median PFS, MFS and OS were 29.6 months, 32.6 months, and 24.1 months, respectively. SBRT was well tolerated with acute and late toxicity rates of 6% and 9%, respectively. Conclusionsd: SBRT appears to be an effective and safe option for elderly pancreatic cancer patients, achieving high local control with minimal toxicity.

We are writing to share important insights and findings regarding the role of staging laparoscopy in the management of pancreatic cancer, as discussed in the recent publication "The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial" [ [1] van Dongen J.C. Versteijne E. Bonsing B.A. et al. The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial. Eur J Surg Oncol. 2023 Apr; 49: 811-817https://doi.org/10.1016/j.ejso.2022.12.011 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ]. This letter aims to highlight the importance of incorporating staging laparoscopy into the diagnostic workflow for patients with pancreatic cancer, in particular those with resectable, borderline resectable and locally advanced disease.

Background and Objective Despite advances in the multidisciplinary management of pancreatic cancer, overall prognosis remains poor, due to early progression of the disease. There is a need to also take action in staging, to make it increasingly accurate and complete, to define the setting of the therapeutic strategy. This review was planned to update the current status of pre-treatment evaluation for pancreatic cancer. Methods We conducted an extensive review, including relevant articles dealing with traditional imaging, functional imaging and minimally invasive surgical procedures before treatment for pancreatic cancer. We searched articles written in English only. Data in the PubMed database, published in the period between January 2000 and January 2022, were retrieved. Prospective observational studies, retrospective analyses and meta-analyses were reviewed and analysed. Key Content and Findings Each imaging modality (endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, positron emission tomography/computed tomography, staging laparoscopy) has its own diagnostic advantages and limitations. The sensitivity, specificity and accuracy for each image set are reported. Data that support the increasing role of neoadjuvant therapy (radiotherapy and chemotherapy) and the meaning of a patient-tailored treatment selection, based on tumour staging, are also discussed. Conclusions A multimodal pre-treatment workup should be searched as it improves staging accuracy, orienting patients with resectable tumors towards surgery, optimizing patient selection with locally advanced tumors to neoadjuvant or definite therapy and avoiding surgical resection or curative radiotherapy in those with metastatic disease.

Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value < 0.5 ng/ml at relapse, while 60–66 Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. Median PSA value at the beginning of salvage radiotherapy was 0.47 ng/ml (range 0.2–17.5 ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.4%) late acute genitourinary grade 3 toxicity. With a median follow-up of 63.5 months, 5 and 7-years relapse-free survival were 70% and 60.7%, respectively. With a median follow-up of 5 years the present study confirms that high-dose salvage radiotherapy to a biological target volume is feasible, with low rate of late toxicity and promising activity.

PURPOSE:In the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer.METHODS AND MATERIALS:Patients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival.RESULTS:Fifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively.CONCLUSIONS:De-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.