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.

How smart is artificial intelligence in organs delineation? Testing a CE and FDA-approved Deep-Learning tool using multiple expert contours delineated on planning CT images.

Background: A CE- and FDA-approved cloud-based Deep learning (DL)-tool for automatic organs at risk (OARs) and clinical target volumes segmentation on computer tomography images is available. Before its implementation in the clinical practice, an independent external validation was conducted. Methods: At least a senior and two in training Radiation Oncologists (ROs) manually contoured the volumes of interest (VOIs) for 6 tumoral sites. The auto-segmented contours were retrieved from the DL-tool and, if needed, manually corrected by ROs. The level of ROs satisfaction and the duration of contouring were registered. Relative volume differences, similarity indices, satisfactory grades, and time saved were analyzed using a semi-automatic tool. Results: Seven thousand seven hundred sixty-five VOIs were delineated on the CT images of 111 representative patients. The median (range) time for manual VOIs delineation, DL-based segmentation, and subsequent manual corrections were 25.0 (8.0-115.0), 2.3 (1.2-8) and 10.0 minutes (0.3-46.3), respectively. The overall time for VOIs retrieving and modification was statistically significantly lower than for manual contouring (p<0.001). The DL-tool was generally appreciated by ROs, with 44% of vote 4 (well done) and 43% of vote 5 (very well done), correlated with the saved time (p<0.001). The relative volume differences and similarity indexes suggested a better inter-agreement of manually adjusted DL-based VOIs than manually segmented ones. Conclusions: The application of the DL-tool resulted satisfactory, especially in complex delineation cases, improving the ROs inter-agreement of delineated VOIs and saving time.

Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial.

PURPOSE: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). METHODS: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. RESULTS: Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. CONCLUSIONS: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.

External validation of a composite bio-humoral index in anal cancer patients undergoing concurrent chemoradiation.

BACKGROUND AND PURPOSE: A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation. MATERIALS AND METHODS: Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale. RESULTS: A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively. CONCLUSION: The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable.

Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice-a fifteen-year journey at a tertiary referral centre.

Pancreatic ductal adenocarcinoma (PDAC) is an increasing disease having a poor prognosis. The aim of the present study was to evaluate the effect of different models of care for pancreatic cancer in a tertiary referral centre in the period 2006-2020. Retrospective study of patients with PDAC observed from January 2006 to December 2020. The demographic and clinical data, and data regarding the imaging techniques used, preoperative staging, management, survival and multidisciplinary tumour board (MDTB) evaluation were collected and compared in three different periods characterised by different organisation of pancreatic cancer services: period A (2006-2010); period B (2011-2015) and period C (2016-2020). One thousand four hundred seven patients were analysed: 441(31.3%) in period A; 413 (29.4%) in B and 553 (39.3%) in C. The proportion of patients increased significantly, from 31.3% to 39.3% (P = 0.032). Body mass index (P = 0.033), comorbidity rate (P = 0.002) and Karnofsky performance status (P < 0.001) showed significant differences. Computed tomography scans (P < 0.001), endoscopic ultrasound (P < 0.001), fine needle aspiration, fine needle biopsy (P < 0.001), and fluorodeoxyglucose-positron emission tomography/computed tomography (P < 0.001) increased; contrast-enhanced ultrasound (P = 0.028) decreased. The cTNM was significantly different (P < 0.001). The MDTB evaluation increased significantly (P < 0.001). Up-front surgery and exploratory laparotomy decreased (P < 0.001), neoadjuvant treatment increased (P < 0.001). The present study showed the evolving knowledge in surgical oncology of pancreatic cancer at a tertiary referral centre over the time. The different models of care of pancreatic cancer, in particular the introduction of the MDTB and the institution of a pancreas unit to the decision-making process seemed to be influential.

Automated Prediction of the Response to Neoadjuvant Chemoradiotherapy in Patients Affected by Rectal Cancer.

BACKGROUND: Rectal cancer is a malignant neoplasm of the large intestine resulting from the uncontrolled proliferation of the rectal tract. Predicting the pathologic response of neoadjuvant chemoradiotherapy at an MRI primary staging scan in patients affected by locally advanced rectal cancer (LARC) could lead to significant improvement in the survival and quality of life of the patients. In this study, the possibility of automatizing this estimation from a primary staging MRI scan, using a fully automated artificial intelligence-based model for the segmentation and consequent characterization of the tumor areas using radiomic features was evaluated. The TRG score was used to evaluate the clinical outcome. METHODS: Forty-three patients under treatment in the IRCCS Sant'Orsola-Malpighi Polyclinic were retrospectively selected for the study; a U-Net model was trained for the automated segmentation of the tumor areas; the radiomic features were collected and used to predict the tumor regression grade (TRG) score. RESULTS: The segmentation of tumor areas outperformed the state-of-the-art results in terms of the Dice score coefficient or was comparable to them but with the advantage of considering mucinous cases. Analysis of the radiomic features extracted from the lesion areas allowed us to predict the TRG score, with the results agreeing with the state-of-the-art results. CONCLUSIONS: The results obtained regarding TRG prediction using the proposed fully automated pipeline prove its possible usage as a viable decision support system for radiologists in clinical practice.

A novel tool for assessing the correlation of internal/external markers during SGRT guided stereotactic ablative radiotherapy treatments.

INTRODUCTION: An in-house developed tool was implemented and validated to investigate the skin surface, hepatic dome, and target displacement for stereotactic ablative radiotherapy (SABR) of thoracic/abdominal lesions using a Surface Guided Radiation Therapy (SGRT) system combined with 4D- images. MATERIALS AND METHODS: Fourteen consecutive patients with tumors near the hepatic dome undergoing SABR treatments were analyzed. For each patient, a planning 4D-CT and five 4D-CBCT images were acquired. The C-RAD technology was also used to register/monitor the position of the skin reference point (SRP) as an external marker representative of patient breathing. The 4D images were imported in the developed tool, and the absolute maximum height (Pmax,dome) of the hepatic dome on the ten respiratory phases was semi-automatically detected. Similarly, the contour of the skin surface was extracted in correspondence with the SRP position. The tool has been validated using an ad hoc modified moving phantom with pre-selected amplitudes and numbers of cycles. The Pearson correlation coefficients and Bland-Altman plots were calculated. RESULTS: There was a strong correlation between the skin motion amplitude based on 4D-CBCT and the C-RAD in all the patients (0.90 ± 0.08). Similarly, the mean ± SD of Pearson correlation coefficients of skin and Pmax,dome movements registered by 4D-CT and 4D-CBCT were 0.90 ± 0.05 and 0.94 ± 0.05, respectively. The mean ± SD of Pearson correlation coefficients comparing the skin and Pmax,dome displacements within each imaging modality were 0.88 ± 0.05 and 0.90 ± 0.05 for 4D-CT and 4D-CBCT, respectively. The SRP displacement during the set-up imaging and the treatment delivery were similar in all the investigated patients. Similar results were obtained for the ad hoc modified phantom in the preliminary validation phase. CONCLUSION: The strong correlation between the tumor/ hepatic dome and skin displacements confirms that the SGRT approach can be considered appropriate for intra- and inter-fraction motion management in SABR therapy.

COVID-19 Pandemic-Adapted Radiotherapy Guidelines: Are They Really Followed?

BACKGROUND: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients' exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs' compliance to these guidelines. METHODS: ROs were asked to fill out a data collection form during patients' first visits in May and June 2020. The collected data included the ROs' age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters. RESULTS: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients' age and lower treatment modifications rate was recorded. CONCLUSION: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

Neoadjuvant Therapy for Resectable Pancreatic Cancer: A New Standard of Care. Pooled Data From 3 Randomized Controlled Trials.

OBJECTIVE: The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome. SUMMARY BACKGROUND DATA: Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations. METHODS: Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards. RESULTS: A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters. CONCLUSION: Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.

Definition of Local Recurrence Site in Resected Pancreatic Adenocarcinoma: A Multicenter Study (DOLORES-1).

The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45-0.53 and 0.58-0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

The Heterogeneity of Skewness in T2W-Based Radiomics Predicts the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Our study aimed to investigate whether radiomics on MRI sequences can differentiate responder (R) and non-responder (NR) patients based on the tumour regression grade (TRG) assigned after surgical resection in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Eighty-five patients undergoing primary staging with MRI were retrospectively evaluated, and 40 patients were finally selected. The ROIs were manually outlined in the tumour site on T2w sequences in the oblique-axial plane. Based on the TRG, patients were grouped as having either a complete or a partial response (TRG = (0,1), n = 15). NR patients had a minimal or poor nCRT response (TRG = (2,3), n = 25). Eighty-four local first-order radiomic features (RFs) were extracted from tumour ROIs. Only single RFs were investigated. Each feature was selected using univariate analysis guided by a one-tailed Wilcoxon rank-sum. ROC curve analysis was performed, using AUC computation and the Youden index (YI) for sensitivity and specificity. The RF measuring the heterogeneity of local skewness of T2w values from tumour ROIs differentiated Rs and NRs with a p-value ≈ 10-5; AUC = 0.90 (95%CI, 0.73-0.96); and YI = 0.68, corresponding to 80% sensitivity and 88% specificity. In conclusion, higher heterogeneity in skewness maps of the baseline tumour correlated with a greater benefit from nCRT.

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Randomized Pilot Trial of Percutaneous Posterior Tibial Nerve Stimulation Versus Medical Therapy for the Treatment of Low Anterior Resection Syndrome: One-Year Follow-up.

BACKGROUND: Low anterior resection syndrome is significantly associated with a deterioration in the quality of life, and its medical treatment is usually ineffective. OBJECTIVE: The aim of the present study was to establish the efficacy of percutaneous tibial nerve stimulation in treating this syndrome. DESIGN: This is a randomized pilot trial with 1-year follow-up. SETTINGS: The study was conducted in a specialized colorectal unit of a tertiary hospital. PATIENTS: Patients who underwent neoadjuvant chemoradiotherapy and low anterior rectal resection for cancer with low anterior resection syndrome score ≥21 and ileostomy closed at least 18 months earlier were included. INTERVENTIONS: Patients were randomly assigned to receive either percutaneous tibial nerve stimulation plus medical treatment (arm A, n = 6) or medical treatment (arm B, n = 6). Low anterior resection syndrome was assessed using symptom severity and disease-specific quality-of-life scores at baseline, at the end of treatment, and at 1-year follow-up. MAIN OUTCOME MEASURES: The primary outcome was a clinical response, defined as a reduction of the low anterior resection syndrome score. RESULTS: Only in group A low anterior resection syndrome score, fecal incontinence severity index, and obstructed defecation syndrome score improved significantly with treatment (35.8 ± 2.5 vs 29.0 ± 3.8 (p = 0.03); 36.8 ± 4.3 vs 18.5 ± 8.0 (p = 0.02); 10.3 ± 3.9 vs 8.0 ± 4.9 (p = 0.009)) and changes were observed in all domains of quality-of-life instruments. In both groups the symptom severity and quality-of-life scores at 1-year follow-up did not differ significantly from those recorded at the end of treatment. LIMITATIONS: The study had a small number of patients and it was underpowered to detect the within-group effect. CONCLUSIONS: Percutaneous tibial nerve stimulation could be an effective treatment for low anterior resection syndrome. Additional studies are warranted to investigate clinical effectiveness in low anterior resection syndrome. See Video Abstract at http://links.lww.com/DCR/B371. ESTUDIO PILOTO ALEATORIO DE ESTIMULACIÓN PERCUTÁNEA DEL NERVIO TIBIAL POSTERIOR VERSUS TERAPIA MÉDICA PARA EL TRATAMIENTO DEL SÍNDROME DE RESECCIÓN ANTERIOR BAJA: UN AÑO DE SEGUIMIENTO: El síndrome de resección anterior baja se asocia con un deterioro significativo en la calidad de vida y su tratamiento médico generalmente es ineficaz.El objetivo del presente estudio fue establecer la eficacia de la estimulación percutánea del nervio tibial en el tratamiento de este síndrome.Este es un estudio piloto aleatorio con 1 año de seguimiento.El estudio se realizó en una unidad colorrectal especializada de un hospital terciario.Se incluyeron pacientes que se sometieron a quimiorradioterapia neoadyuvante y resección rectal anterior baja por cáncer con puntaje de síndrome de resección anterior baja ≥ 21 e ileostomía cerrada al menos 18 meses antes.Los pacientes fueron asignados aleatoriamente para recibir estimulación percutánea del nervio tibial + tratamiento médico (brazo A, n = 6) o tratamiento médico (brazo B, n = 6). El síndrome de resección anterior baja se evaluó utilizando puntajes de la gravedad de los síntomas y de calidad de vida específicos de la enfermedad al inicio, al final del tratamiento y al año de seguimiento.El resultado primario fue una respuesta clínica, definida como una reducción de la puntuación del síndrome de resección anterior baja.Solo en el grupo A, el puntaje del síndrome de resección anterior baja, el índice de severidad de incontinencia fecal y el puntaje del síndrome de defecación obstruida mejoraron significativamente con el tratamiento (35.8 ± 2.5 vs 29 ± 3.8, p = 0.03; 36.8 ± 4.3 vs 18.5 ± 8.0, p = 0.02; 10.3 ± 3.9 vs 8.0 ± 4.9, p = 0.009, respectivamente) y se observaron cambios en todos los dominios de los instrumentos de calidad de vida. En ambos grupos, los puntajes de severidad de los síntomas y de calidad de vida al año de seguimiento no difirieron significativamente de los registrados al final del tratamiento.El estudio tuvo un pequeño número de pacientes y no logró suficiente poder para detectar el efecto dentro de grupo.La estimulación percutánea del nervio tibial podría ser un tratamiento efectivo para el síndrome de resección anterior baja. Se requieren estudios adicionales para investigar la efectividad clínica en el síndrome de resección anterior baja. Consulte Video Resumen http://links.lww.com/DCR/B371.

Stereotactic body radiotherapy vs conventionally fractionated chemoradiation in locally advanced pancreatic cancer: A multicenter case-control study (PAULA-1).

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut-offs:

Intraoperative electrochemotherapy in locally advanced pancreatic cancer: indications, techniques and results-a single-center experience.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is usually treated with chemoradiotherapy with poor results. The aim of the study was to assess whether intraoperative electrochemotherapy could be proposed as additional therapy in treating LAPC. METHODS: Observational study of patients affected by LAPC who underwent intraoperative electrochemotherapy (ECT) after chemoradiotherapy. Data at diagnosis, at restaging and short and long-term outcomes, including assessment of quality of life, were collected for each patient. RESULTS: Five patients underwent ECT: in four cases, the tumours were located in the head and, in one, in the body of the pancreas. Preoperative chemotherapy consisted mainly of six cycles of modified Folfirinox. At restaging, the serum value of carbohydrate antigen (Ca 19-9) and tumour size were reduced; however, the vascular involvement did not change. No downstaging was recorded. The ECT procedure was performed using at least four needles with a mean duration time of 27 min (range 15-40). No postoperative mortality or major complications were reported. The mean length of stay (LOS) was 8 days (range 5-14). Four patients were alive and well at the end of the study, while one patient died from disease progression. The mean follow-up was 20.8 months (range 9-34) from diagnosis and 9.4 months (range 2-19) from ECT. The quality of life was good and there was improvement in pain/discomfort. CONCLUSIONS: Electrochemotherapy could be proposed as a simple, feasible and safe palliative additional treatment in LAPC without progression after chemoradiotherapy. It seems to allow a good quality of life and pain improvement.

Higher Biologically Effective Dose Predicts Survival in SBRT of Pancreatic Cancer: A Multicentric Analysis (PAULA-1).

AIM: The purpose of the present multicentric study was to review stereotactic body radiotherapy (SBRT) with or without chemotherapy (CHT) experience in locally advanced pancreatic cancer (LAPC). Endpoints were overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). Several parameters' impact on these outcomes was assessed. MATERIALS AND METHODS: Fifty-six patients with LAPC undergoing SBRT+/-CHT were included. SBRT median BEDα/ß10Gy was 48.0 Gy (range=28.0-78.7). Survival curves were calculated by Kaplan-Meier method. A Cox regression model was fitted. RESULTS: At a median follow-up of 15.0 months, 2-year OS, LC, DMFS were: 33.8% 55.4%, and 22.9%, respectively. Patients treated with BEDα/ß10Gy≥48 Gy showed improved OS (p=0.020) and LC (p=0.024). At multivariate analysis, BEDα/ß10Gy≥48 Gy was significantly associated to both higher OS (p=0.042) and LC (p=0.045), while post-SBRT CHT improved DMFS (p=0.003). CONCLUSION: SBRT proved to be tolerable and effective in LAPC. Moreover, BEDα/ß10Gy≥48 Gy was significantly correlated with improved OS and LC.

Anorectal adenocarcinoma recurrence successfully treated with electrochemotherapy: a case report.

Anal canal adenocarcinoma is generally treated like rectal cancer. Surgery is the standard treatment in early stages and neoadjuvant chemoradiation in locally advanced tumors. Local recurrences treatment paradigm often depends on the previous therapies of either surgery or radiotherapy or systemic therapy. We present the case of a patient with tubulovillous adenocarcinoma of the anal canal which relapsed after chemoradiation. The patient refused salvage surgery and was treated with definitive electrochemotherapy under general anesthesia. Tumor electroporation performed with the insertion of three needles in the recurred site was preceded by an intravenous bolus of bleomycin. After the administered treatment, the patient showed a complete clinical response. A year after electrochemotherapy, the patient is free from local disease with excellent preservation of the sphincter function. Electrochemotherapy may be considered as an alternative to surgery in small lesion in the anorectal region when other approaches are excluded.

Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival.

BACKGROUND: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. RESULTS: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. CONCLUSIONS: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

An atlas for clinical target volume definition, including elective nodal irradiation in definitive radiotherapy of biliary cancer.

Radiotherapy (RT) is a treatment option for advanced biliary tract cancer (BTC), often combined with sequential and/or concurrent chemotherapy. The use of modern RT techniques requires accurate clinical target volume (CTV) definition and delineation. However, guidelines for CTV delineation in BTC are lacking. Therefore, the aim of this study was to propose a computer tomography (CT) atlas for CTV definition of BTC. We previously proposed guidelines to define the nodal CTV (CTV-N) in BTC. In this study, based on a literature analysis, we defined the margins to be added to the gross tumor volume (GTV; subclinical and microscopic disease) to define the primary tumor CTV (CTV-T). An abdominal contrast enhanced planning CT scan was performed on three different patients with unresectable intrahepatic cholangiocarcinoma (CC), extrahepatic CC and gallbladder cancer. The GTV and anatomical reference structures were outlined on CT images. Then, based on our guidelines, the CTV-T and CTV-N were delineated and merged to define the final CTV in the three patients. An atlas, showing the defined CTV, was generated from the reference CT images to illustrate the CTV for intra-hepatic CC, extra-hepatic CC and gallbladder cancer. This atlas can be used as an aid for CTV definition in patients with BTC treated with modern RT techniques.

Magnetic resonance imaging (MRI) compared with computed tomography (CT) for interobserver agreement of gross tumor volume delineation in pancreatic cancer: a multi-institutional contouring study on behalf of the AIRO group for gastrointestinal cancers.

BACKGROUND: Due to the high soft tissue resolution, magnetic resonance imaging (MRI) could improve the accuracy of pancreatic tumor delineation in radiation treatment planning. A multi-institutional study was proposed to evaluate the impact of MRI on inter-observer agreement in gross tumor volume (GTV) and duodenum delineation for pancreatic cancer compared with computer tomography (CT). MATERIAL AND METHODS: Two clinical cases of borderline resectable (Case 1) and unresectable (Case 2) pancreatic cancer were selected. In two sequential steps, diagnostic contrast-enhanced CT scan and MRI sequences were sent to the participating centers. CT-GTVs were contoured while blinded to MRI data sets. DICE index was used to evaluate the spatial overlap accuracy. RESULTS: Thirty-one radiation oncologists from different Institutions submitted the delineated volumes. CT- and MRI-GTV mean volumes were 21.6 ± 9.0 cm3 and 17.2 ± 6.0 cm3, respectively for Case 1, and 31.3 ± 15.6 cm3 and 33.2 ± 20.2 cm3, respectively for Case 2. Resulting MRI-GTV mean volume was significantly smaller than CT-GTV in the borderline resectable case (p < .05). A substantial agreement was shown by the median DICE index for CT- and MRI-GTV resulting as 0.74 (IQR: 0.67-0.75) and 0.61 (IQR: 0.57-0.67) for Case 1; a moderate agreement was instead reported for Case 2: 0.59 (IQR:0.52-0.66) and 0.53 (IQR:0.42-0.62) for CT- and MRI-GTV, respectively. CONCLUSION: Diagnostic MRI resulted in smaller GTV in borderline resectable case with a substantial agreement between observers, and was comparable to CT scan in interobserver variability, in both cases. The greater variability in the unresectable case underlines the critical issues related to the outlining when vascular structures are more involved. The integration of MRI with contrast-enhancement CT, thanks to its high definition of tumor relationship with neighboring vessels, could offer a greater accuracy of target delineation.