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The first actions and provisions in a Southern Italy Department of Radiation Oncology are described at the inception of the COVID-19 pandemic.

4577 Background: Cancer is recognized as a major risk factor for severe COVID19. However little is known about the impact of oncologic treatments in the evolution of the disease. On the other hand, the influence of SARS-CoV2 in cancer response remains to be established. We aim to determine both aspects in renal cancer patients receiving different therapeutic options. Methods: We designed a retrospective case-control study to compare the outcome of patients with advanced renal cancer who developed COVID19 under antiangiogenic treatment (cohort A [ChA]) vs immunotherapy (alone or in combination: cohort B [ChB]) vs matched controls (cohort C [ChC]). Controls were renal cancer patients who were not infected during the period of study. One control per case was selected regarding age, gender, kidney cancer histology and type of treatment. Results: From May 20 to Feb 21, 80 patients were recruited. We present the first 55 patients included (15 ChA, 16 ChB and 20 ChC, 4 patients were screening failure) from 13 centers in Spain. Median age was 62 (range 25 to 88) overall and 62 (range 44 to 88) in Ch A, 64,5 (range 42 to 83) in ChB and 61 (range 41 to 77) in ChC. 38 patients were male and 13 were female. Overall 45 cases were clear cell carcinoma (13 ChA, 14 ChB and 18 ChC), 4 papillary (1 ChA, 2 ChB and 1 ChC), 1 chromophobe (ChA) and 1 unclassified (ChC). Median number of prior lines of treatment was 2 (range 1 to 6) overall, (1 [range 1 to 4] in ChA, 2 [range 1 to 4] in ChB and 2 [range 1 to 6] in ChC). 25 patients required treatment interruptions (8 in ChA [32%], 14 in ChB [56%] and 3 [12%] in ChC). 9 patients were hospitalized (4 in Ch A, 5 in ChB and none in ChC) for a median of 10 days (range 4 to 16) overall (7 [range 4 to 14] in ChA and 12 [range 5 to 16] in ChB). No patient required ICU admission. Best tumor response was complete or partial (CR+PR) in 25 patients (5 [20%] in ChA, 9 [36%] in ChB and 11 [44%] in ChC). Clinical benefit (CR+PR+stable disease) was observed in 38 patients (11 [28,9%] in ChA, 10 [26,3%] in ChB and 17 [44,7%] in ChC). One patient in ChB died (due to COVID19). Updated results will be presented. Conclusions: Patients with renal cancer who developed COVID19 held treatment more frequently and presented lower clinical benefit rates than non infected cases. Patients receiving immunotherapy required more frequent dose interruptions and longer hospitalizations than cases on antiangiogenics. These results point to an impact of SARS-CoV2 in renal cancer outcome. Therapies administered to treat renal cancer, could play a role in the evolution of COVID19.

Purpose One of the rarest gastrointestinal neoplasm is small bowel cancer. Experience with its treatment modalities is limited. Stereotactic ablative radiation therapy (SABR) has improved, with image-guided radiation therapy becoming a curative option in many tumors. Especially when surgery cannot be performed due to comorbidities, SABR provides a good toxicity profile and an excellent tumor control rate owing to its specific schedule: high dose on a limited and well-defined area. Methods An 83-year-old man had arterial hypertension and congestive cardiomyopathy, with recent history of upper abdominal pain, weight loss over 10 kg, and progressive severe fatigue. The patient underwent endoscopy that showed a large mass partially obstructing the second part of the duodenum; a biopsy revealed a moderately differentiated adenocarcinoma. A staging CT scan confirmed localized disease. Due to the patient's age and comorbidities, a SABR was proposed as the preferred treatment. In order to localize the tumor during radiotherapy sessions, surgical clips were placed endoscopically next to the lesion as fiducial markers. The patient received 25 Gy in 5 fractions on alternate days. Results Resolution of duodenal obstruction and bleeding lasted for 14 months. The patient died of myocardial infarction. Conclusions This case suggests that SABR could have a role in the palliative treatment of small bowel cancers, with good toxicity profile, particularly in patients for whom surgical treatment is not a viable option.

Background and purpose: Capecitabine-based radiochemotherapy (cbRCT) is standard for preoperative long-course radiochemotherapy of locally advanced rectal cancer. This prospective, parallel-group, randomised controlled trial investigated two intensification regimens. cT4 lesions were excluded. Primary objective: pathological outcome (TRG 1-2) among arms.Materials and methods: Low-located cT2N0-2M0, cT3N0-2M0 (up to 12 cm from anal verge) presentations were treated with cbRCT randomly intensified by either radiotherapy boost (Xelac arm) or multidrug concomitant chemotherapy (Xelox arm). Xelac: concomitant boost to bulky site (45 Gy/1.8 Gy/die, 5 sessions/week to the pelvis, + 10 Gy at 1 Gy twice/week to the bulky) plus concurrent capecitabine (1650 mg/mq/die). Xelox: 45 Gy to the pelvis + 5.4 Gy/1.8 Gy/die, 5 sessions/week to the bulky site + concurrent capecitabine (1300 mg/mq/die) and oxaliplatin (130 mg/mq on days 1,19,38). Surgery was planned 7-9 weeks after radiochemotherapy.Results: From June 2005 to September 2013, 534 patients were analysed: 280 in Xelac, 254 in Xelox arm. Xelox arm presented higher G >= 3 haematologic (p = 0.01) and neurologic toxicity (p < 0.001). Overall, 98.5% patients received curative surgery. The tumour regression grade distribution did not differ between arms (p = 0.102). TRG 1+2 rate significantly differed: Xelac arm 61.7% vs. Xelox 52.3% (p = 0.039). Pathological complete response (ypT0N0) rates were 24.4 and 23.8%, respectively (p non-significant). Median follow-up: 5.62 years. Five-year disease-free survival rate were 74.7% (Xelac) and 73.8% (Xelox), respectively (p = 0.444). Five-year overall survival rate were 80.4% (Xelac) and 85.5% (Xelox), respectively (p = 0.155).Conclusion: Xelac arm significantly obtained higher TRG1-2 rates. No differences were found about clinical outcome. Because of efficacy on TRG, inferior toxicity and good compliance, Xelac schedules or similar radiotherapy dose intensification schemes could be considered as reference treatments for cT3 lesions. (C) 2018 Published by Elsevier B.V.

The impact of new treatments for rectal cancer has substantially improved patients clinical outcomes in the last years, but still worldwide colorectal cancer remains the third most common. In 2000, colorectal cancer was responsible for 7.9% of the world’s cancer deaths, with 492,000 deaths; it accounted for 9.4% of the world’s new cancers registered, with 945,000 cases diagnosed [1, 2].

Purpose Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient’s sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict. Methods Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy. The ratio of distant metastasis (DM) and local recurrence (LR) rates was used to identify patient characteristics that increase the risk of recurrences. Findings The DM/LR ratio decreased to a plateau in the first 2 years, revealing it to be a critical follow-up period. According to the patterns of recurrences, three patient groups were identified: 5–15% had pCR and were disease free after 2 years (excellent prognosis), 65–75% had no pCR but were disease free (good prognosis) and 15–30% had neither pCR nor 2yDFS (poor prognosis). Interpretation Compared with pCR, 2yDFS is a stronger predictor of OS. To adapt treatment most efficiently, accurate prediction models should be developed for pCR to select patients for organ preservation and for 2yDFS to select patients for more intensified treatment strategies.

Resumen Objetivos 1) Valorar el seguimiento de las recomendaciones no farmacologicas para el tratamiento de la hipertension arterial (HTA). 2) Analizar la relacion entre el seguimiento de las medidas no farmacologicas y el control de la presion arterial. Metodos Estudio transversal descriptivo realizado en un centro de atencion primaria de Murcia. Se incluyen 102 pacientes diagnosticados y tratados de HTA desde hace mas de un ano. Se valora su habito tabaquico, consumo de alcohol, practica de ejercicio fisico y consumo de alimentos ricos en sal mediante cuestionario clinico especifico en entrevista bidireccional. A todos ellos se les mide la excrecion de sodio en orina de 24 h. Resultados El 19,6% de los pacientes son fumadores. El 7,8% de los pacientes presentan consumo excesivo alcohol. El 40,2% de los pacientes no realizan ejercicio fisico ningun dia a la semana. El 93,1% presentan una excrecion urinaria de sodio > 100 mmol/24 h. Globalmente solo el 6,9% de pacientes del total de la muestra cumplen todas las medidas no farmacologicas para el tratamiento de la HTA. De los pacientes que cumplen todas las medidas del tratamiento no farmacologico, el 85,7% presentan buenos controles de presion arterial. Los pacientes que no cumplen las medidas no farmacologicas, presentan una odds ratio de 9,4 respecto a tener peores controles tensionales que los que las cumplen (p Conclusiones El cumplimiento de las medidas no farmacologicas para el tratamiento de la HTA es muy bajo. Los pacientes que tienen un mejor cumplimiento del tratamiento no farmacologico presentan mejores controles de su presion arterial.

Background Our objective was evaluate the outcome of primary clinical T4M0 extraperitoneal rectal cancer treated by neoadjuvant radiochemotherapy. Prognosis of clinical T4 rectal cancer is poor. Preoperative chemoradiation therapy may be beneficial. The results obtained are unclear due to lack of objective and strictly applied staging methods. Methods Patients with primary, clinical, T4MO, extraperitoneal rectal cancer, defined by transrectal ultrasonography, computed tomography or magnetic resonance imaging, were considered. Intraoperative radiotherapy and adjuvant chemotherapy were employed in some patients after curative resection (R0). Variables influencing the possibility to perform an R0 resection and a sphincter-saving procedure were investigated as predictors of outcome. Results 100 patients were included. R0 resection was performed in 78 patients. R0 resection rate was greater in females (93% vs 67%) and in responders to neoadjuvant chemoradiation (94% vs 60%). The ability to perform a sphincter-saving procedure was 57%, greater in middle rectal location (85% vs 51%) and in responders to the chemoradiation (70% vs 47%). Median follow-up was 31 months (range, 4–136). Local recurrences were found in 7 patients (10%). Five-year local control in R0 patients was 90% and better in the IORT group (100%). Distant relapse occurred in 24 patients (30%). Five-year overall survival was 59%, and was better after an R0 versus an R1 or R2 resection (68% vs 22%). Overall and disease free survival in R0 patients improved after overall downstaging. Adjuvant chemotherapy given in addition to the neoadjuvant therapy did not appear to offer benefit in improving survival. Conclusion A multimodal approach enabled us to obtain a 5-year overall survival of about 60%. IORT increased local control. The role of adjuvant chemotherapy needs to be further investigated.

Purpose To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti–epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. Methods and Materials Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. Results A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). Conclusions Gefitinib can be associated with 5-FU–based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.

When the surgeon analyzes the ongoing literature on the evidence of the neoadjuvant approaches to rectal cancer finds a true paradox: from one side they seem to offer a relative less relevant contribute through the time, in fact whereas in the Swedish trial preoperative radiation yielded a significant improvement of local control and survival, after the introduction of TME the contribution of preoperative chemoradiation is relegate to local control with no or poor influence on survival, even if the absolute 5-year survival rate moved from 40% of the ?70 to 60-65% of the latest years1-3. From other side the growing evidence of an incidence of pCR approaching to 30%4, seems to identify a subset of patients with more favorable prognosis to neoadjuvant treatments5-6. Furthermore, the overall evidence that 30- 35% of rectal cancer patients treated with multimodality therapy still die from cancer namely by distant metastases in spite of the 4-8 % of absolute benefit of adjuvant 5Fu based adjuvant chemotherapy7, seems to vanish the efforts of the further optimization of the local treatments (surgery and radiotherapy) and of the ongoing modality of delivery the chemotherapeutic agents. We would like to address the main evidences from the literature and the main uncertainties that the surgeon could face to propose a combined treatment to his rectal cancer patient.

To evaluate in two different settings - clinical practice and education/training - the reliability, time efficiency and the ideal sequence of an atlas-based auto-segmentation system in pelvic delineation of locally advanced rectal cancer.Fourteen consecutive patients were selected between October and December 2011. The images of four were used as an atlas and 10 used for validation. Two independent operators participated: a Delineator to contour and a Reviewer to perform an independent check (IC). The CTV, pelvic subsites and organs at risk were contoured in four different sequences. These included A: manual; B: auto-segmentation; C: auto-segmentation + manual revision; and D: manual + auto-segmentation + manual revision. Contouring was performed by the Delineator using the same planning CT. All of them underwent an IC by a Reviewer. The time required for all the contours were recorded and overlapping evaluation was assessed using a Dice coefficient.In the clinical practice setting there have been 13 minutes time saved between sequences A versus sequences B (from 38 to 25 minutes, p = 0.002), a mean Dice coefficient in favor of sequences A for CTV and all subsites (p = 0.0195). In the educational/training setting there have been 35.2 minutes time saved between sequences C and D 8 (from 73.1 min to 37.9 min, p = 0.002).The preliminary data suggest that the use of an atlas-based auto-contouring system may help improve efficiencies in contouring in the clinical practice setting and could have a tutorial role in the educational/training setting.

Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusion The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up ( http://www.predictcancer.org ).

Aims The purpose of this study was to translate the Memorial Sloan Kettering Cancer Centre (MSKCC) Bowel Function Instrument into Italian and to test its psychometric validity and reliability in a sample of Italian rectal cancer patients. Methods The MSKCC questionnaire was translated into Italian using a standard procedure of double-back translation. Construct validity was tested using a factor analysis and internal reliability was estimated using the Cronbach’s alpha coefficient. Concurrent validity was determined by correlations with European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 quality of life scales. A non-parametric analysis of variance was used to establish the discriminant validity of the questionnaire. Test-retest reliability was assessed using the intra-class correlation coefficient. Results 124 rectal cancer patients participated in the validation study. The number of missing items was 2.2%. The factorial structure was found to be quite similar to the original one and the internal reliability was 0.7 for urgency, 0.6 for frequency, and 0.7 for dietary subscale. The test-retest reliability was acceptable with one exception: the dietary subscale showed a low reproducibility (ICC = 0.4). All three subscales showed a significant correlation with the QLQ-C30 and QLQ-CR38 domains and were able to discriminate several groups of clinical relevance. Conclusions The Italian version of the MSKCC Bowel Function Instrument shows acceptable psychometric properties and can be considered a valuable and specific instrument to assess bowel functions in rectal cancer patients, both for research purposes and in clinical practise.

PURPOSE: Although surgery remains the most important treatment of rectal cancer, the management of this disease has evolved to become more multidisciplinary to offer the best clinical outcome. The International Conference on Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) had the due to identify the degree of consensus that could be achieved across a wide range of topics relating to the management of rectal cancer helping shape future programs, investigational protocols and guidelines for staging and treatment throughout Europe. MATERIALS AND METHODS: Consensus was achieved using the Delphi method. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by topic, and a series of statements were developed. Each committee member commented and voted, sentence by sentence three times. Sentences which did not reach agreement after voting round # 2 were openly debated during the Conference in Perugia (Italy) December 2008. The Executive Committee scored percentage consensus based on three categories: 'large consensus', 'moderate consensus', 'minimum consensus'. RESULTS: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of members. All chapters were voted on by at least 75% of the members, and the majority was voted on by 85%. CONCLUSIONS: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe. In spite of substantial progress, many research challenges remain.