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To reach a consensus on recommendations for the management of high-risk and post-operative non-metastatic prostate cancer by a group of Radiation Oncologists in Catalonia dedicated to prostate cancer.A modified Delphi approach was employed to reach consensus on controversial topics in Radiation Oncology on high-risk non-metastatic (eight questions) and post-operative (eight questions) prostate cancer. An agreement of at least 75% was considered as consensus. The survey was electronically sent 6 weeks before an expert meeting where topics were reviewed and discussed. A second-round survey for the controversial questions only was sent and answered by participants after the meeting.After the first round of the survey, 19 experienced Radiation Oncologists attended the meeting and 74% fulfilled the second-round online questionnaire. An agreement of 9 of the 16 questions was accounted for the first round. After the meeting, an additional agreement was reached in 3 questions leading to a final consensus on 12 of the 16 questions. There are still controversial topics like the use of PET for staging of high-risk and post-operative non-metastatic prostate cancer and the optimal dose to the prostate bed in the salvage setting.This consensus contributes to establish recommendations and a framework to help in prostate cancer radiation therapy and pharmacological management in daily clinical practice of high-risk and post-operative non-metastatic prostate cancer.

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5–87.5% of cases); presentation to multidisciplinary tumour board (2.5–100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42–102.5 days); number of treatment interruptions ≥ 1 day (7.5–97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.

Objectives This study aimed to develop mapping algorithms from the Expanded Prostate Cancer Index Composite (EPIC) and the Short-Form (SF) Health Surveys to the Patient-Oriented Prostate Utility Scale (PORPUS), an econometric instrument specifically developed for patients with prostate cancer. Methods Data were drawn from 2 cohorts concurrently administering PORPUS, EPIC-50, and SF-36v2. The development cohort included patients who had received a diagnosis of localized or locally advanced prostate cancer from 2017 to 2019. The validation cohort included men who had received a diagnosis of localized prostate cancer from 2014 to 2016. Linear regression models were constructed with ln(1 − PORPUS utility) as the dependent variable and scores from the original and brief versions of the EPIC and SF as independent variables. The predictive capacity of mapping models constructed with all possible combinations of these 2 instruments was assessed through the proportion of variance explained (R2) and the agreement between predicted and observed values. Validation was based on the comparison between estimated and observed utility values in the validation cohort. Results Models constructed with EPIC-50 with and without SF yielded the highest predictive capacity (R2 = 0.884, 0.871, and 0.842) in comparison with models constructed with EPIC-26 (R2 = 0.844, 0.827, and 0.776). The intraclass correlation coefficient was excellent in the 4 models (>0.9) with EPIC and SF. In the validation cohort, predicted PORPUS utilities were slightly higher than those observed, but differences were not statistically significant. Conclusions Mapping algorithms from both the original and the abbreviated versions of the EPIC and the SF Health Surveys allow estimating PORPUS utilities for economic evaluations with cost-utility analyses in patients with prostate cancer.

Background: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined. Aim: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC). Methods: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014. Results: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS. Conclusions: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients. Sin financiación No data JCR 2020 0.367 SJR (2020) Q3, 253/354 Oncology No data IDR 2020 UEM

Introduction No study has examined structural brain changes specifically associated with chemotherapy in a lung cancer population. The aim of this cross-sectional study was to assess differences in brain structure between small-cell lung cancer patients (C+) following chemotherapy, non–small-cell lung cancer patients (C−) before chemotherapy and healthy controls (HC). Methods Twenty-eight small-cell lung cancer patients underwent a neuropsychological assessment and a structural magnetic resonance imaging, including T1-weighted and diffusion tensor imaging to examine gray matter density and white matter (WM) integrity, respectively, 1 month following completion of platinum-based chemotherapy. This group was compared with 20 age and education-matched non–small-cell lung cancer patients before receiving chemotherapy and 20 HC. Results Both C+ and C− groups exhibited cognitive impairment compared with the HC group. The C+ group performed significantly worse than HC in verbal fluency and visuospatial subtests; C− performed significantly worse than both C+ and HC in verbal memory. Voxel-based morphometry analysis revealed lower gray matter density in the insula and parahippocampal gyrus bilaterally, and left anterior cingulate cortex in C+ compared with HC. Diffusion tensor imaging indices showed focal decreased WM integrity in left cingulum and bilateral inferior longitudinal fasciculus in the C+ group and more widespread decreased integrity in the C− group compared with the HC group. Conclusion This study demonstrates that lung cancer patients exhibit cognitive impairment before and after chemotherapy. Before the treatment, C− showed verbal memory deficits as well as a widespread WM damage. Following treatment, the C+ group performed exhibited lower visuospatial and verbal fluency abilities, together with structural gray matter and WM differences in bilateral regions integrating the paralimbic system.

The present study aimed to explore the functional connectivity differences in Resting State Networks (RSNs) induced by cancer and chemotherapy in Lung Cancer (LC) patients using an Independent Component Analysis (ICA). Three matched groups of 15 LC patients following Chemotherapy (C+), 15 LC patients before Chemotherapy (C-) and 15 Healthy Controls (HC) were included. Analysis was performed using ICA and a multivariate pattern analysis (MVPA) to classify groups based on profiles of functional connectivity. We found significant differences in four of the RSN identified: Default Mode Network (DMN), Predominantly Left and Right Anterior Temporal Network, and Cerebellum Network. Whereas DMN showed decreased connectivity, the other RSNs exhibited increased connectivity in both LC groups compared to HC and in C+ in comparison to C-. MVPA discriminated significantly and accurately between all groups. Our study showed that disrupted functional connectivity associated with cancer and chemotherapy-induced cognitive deficits is not only related to DMN decreased connectivity abnormalities but also to an increased connectivity of other RSNs, suggesting a potential compensatory mechanism. Graphical abstract.

e20093 Background: Thoracic radiotherapy (TRT) for extensive stage small-cell lung cancer (ES-SCLC) patients is controversial. Slotman et al. (2015) demonstrated a 2-year overall survival (OS) benefit for patients who received TRT after chemotherapy (CT) and prophylactic cranial irradiation (PCI), but obtaining a median OS of 8 months (m). We wanted to confirm results of Slotman’s work in a real-world setting with higher doses of TRT. Methods: We retrospectively reviewed 67 patients with ES-SCLC treated between 1995 and 2015, after completing CT administration. Patients with initial brain metastasis and those who rejected PCI were excluded. All of them received PCI. All patients were followed until death. Disease-specific survival (DSS), disease-free survival (DFS) and OS were analyzed and computed with Kaplan-Meier method, groups were compared with log-rank test. Adjusted hazard risk (HR) of death for TRT was estimated through multivariate Cox model. Results: Patients (59 male, 8 female) with median age 64 years (42-79) had a median Karnofsky performance status (KPS) of 80. Twenty-three patients received high doses TRT (mean dose: 45.4 Gy). No significant differences between groups were found in age, gender, KPS, number of metastatic sites, residual thoracic disease or smoke activity. Non-TRT patients had more metastatic lesions. Median OS for TRT-patients was 19.9 m and 11.2 m for non-TRT patients (p = 0.01). DSS was 23.4 m for TRT-patients and 13.5 m for non-TRT patients (p = 0.007). For TRT-patients and non-TRT patients, median DFS were 15.5 and 8.3 m (p = 0.001), respectively. In the multivariate analysis, TRT (p = 0.003, HR 0.35), KPS (p = 0.012, HR 0.95) and residual thoracic disease (p = 0.02, HR 3.30) were independent prognostic factors for survival. The best benefit was obtained for those patients with consolidative TRT (CTRT): OS of 24.7, DSS of 27.4 and DFS of 15.9 m, compared with 13.4 (p = 0.003), 13.9 (p = 0.003) and 8.5 m (p = 0.007), respectively, for patients not treated with CTRT. Conclusions: TRT impacts positively in OS, DSS and PFS and should be administered to ES-SCLC patients who complete CT and PCI. High TRT doses could achieve better results than those described for low TRT doses.

Purpose Although concurrent chemotherapy and radiation is the standard approach for good risk unresectable stage III non-small cell lung cancer (NSCLC) patients, there is no optimal concurrent chemotherapy regimen. Administration of chemotherapy at full dose with maximal activity against local and micrometastatic disease is highly desirable. This study tested the feasibility of 3 cycles of full dose cisplatin and pemetrexed concurrent with definitive thoracic radiotherapy followed by consolidation pemetrexed, without the dose-limiting toxicity (DLT) exceeding 33% of the patients. Methods Patients with unresectable stage III NSCLC, good performance status and no serious comorbidity were eligible. Patients received thoracic radiation to a dose of 66Gy concurrently with three 21-day cycles of pemetrexed 500mg/m 2 , and cisplatin at escalating doses from 60 to 75mg/m 2 . Consolidation chemotherapy of pemetrexed 500mg/m 2 was provided for 3 more 21-day cycles. Cisplatin doses were escalated as far as no more than 1/3 of the patients in a level developing dose limiting toxicities (DLT). Results Fifteen eligible patients were enrolled: nine in the first dose level and 3 in the second and third dose levels respectively. Two out of 9 patients in the first dose level experienced DLT (grade 3 esophagitis resulting in delay in treatment administration). The major serious acute toxicities were esophagitis (40%) and febrile neutropenia (20%). With a median follow up time of 22 months, median time to progression and overall survival has not been reached. The rate of survival at 24 months was 57.5% (95% CI: 27.5–87.4%) of the patients. Conclusions Three systemic dose levels of pemetrexed and cisplatin could be administered concurrently with radiotherapy. The rate of survival at 24 months was encouraging.

Introduction The toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. Methods Twenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire was also completed. Results Patients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. Conclusions This longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects.

Resumen Objetivos A raiz de una incidencia de sobredosis detectada en el servicio de radioterapia, se puso en marcha un proyecto de analisis y eliminacion de riesgos para aumentar la seguridad de los pacientes. Material y metodo Se aplico el analisis modal de fallos y efectos (AMFE), un instrumento analitico aplicado en varios hospitales de Estados Unidos. Como exige la metodologia, se cuantificaron los riesgos de cada modo de fallo en una escala de 1:1.000 utilizando el indice NPR (numero de priorizacion del riesgo). En una primera fase de mejora, se definio el nivel de actuacion como NPR > 100. Se detectaron varios riesgos en los protocolos actuales y se eliminaron todos ellos mediante redefinicion de circuitos, controles y verificaciones adicionales, listas de comprobacion y auditorias internas, entre otros. Posteriormente, se introdujo un sistema de gestion de la calidad segun ISO9001, se definio una serie de indicadores y la direccion se implico realizando revisiones mensuales de los resultados. Resultados Se implantaron 100 acciones de mejora. El indice de riesgo calculado despues de haber tomado las acciones bajo significativamente y aumento la seguridad. Las mejoras realizadas aseguran el mantenimiento del grado de seguridad logrado. Conclusiones La experiencia muestra que se puede identificar objetivamente los riesgos de cada paso que damos y destinar los escasos recursos de que disponemos a los procesos o actividades donde el riesgo es mayor, mediante mejoras metodologicas de nuestros protocolos de trabajo.

Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.

PURPOSE: The long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the changes in neuropsychological variables and brain structure in a group of long-term SCLC survivors treated with PCI. PATIENTS AND METHODS: Eleven long-term SCLC patients, who underwent PCI at least two years before were compared to an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging (MRI: T1-weigthed and diffusion-weighted imaging, DTI). Voxel-based morphometry (T1-VBM) and Tract-based Spatial Statistics (DTI-TBSS) were used to analyze gray matter (GM) and white matter (WM) integrity, respectively. RESULTS: Nearly half (45%, n = 5) of the SCLC patients met criteria for cognitive impairment in relation to verbal abilities, processing speed and visual memory. In addition, SCLC patients showed significant decreases of GM in subcortical regions such are the basal ganglia bilaterally (including the putamen and caudate), bilateral thalamus and right insula, together with lower WM integrity of the entire corpus callosum. CONCLUSION: This is the first study to demonstrate neuropsychological deficits together with brain-specific structural differences of both GM and WM in long-term SCLC survivors. Our results suggest that PCI therapy is associated with the development of permanent long-term cognitive and structural brain effects in a SCLC population.

Background Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes. Methods A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months. Results During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. Conclusions Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.

Primary lymphomas of the larynx are extremely rare. Even more unusual is their association with rheumatologic diseases. Some cases of lymphoma have developed after chemotherapy for rheumatologic diseases, suggesting that the treatment may contribute to the development of lymphoma. The converse can also occur-the development of rheumatologic disease after a primary laryngeal lymphoma-but that is even rarer. We report a case of primary extranodal marginal zone B-cell MALT (mucosa-associated lymphoid tissue)lymphoma of the larynx in a 42-year-old woman treated with involved-field radiotherapy who developed systemic lupus erythematosus (SLE) 1 year after the lymphoma diagnosis. Currently, the patient remains in remission 8 years after her diagnosis. The SLE, for which she is receiving maintenance therapy, is stable.

e22139 Background: During the last years, new predictive and less frequent biomarkers have emerged in NSCLC, such as ROS1 translocation (ROS1t), HER2 mutations (HER2m) and BRAF mutations (BRAFm). W...

e17504 Background: The purpose of this study is to evaluate the tolerance and suitability of treatment with high dose radiotherapy (RT) fractions (fr) for fragile patients (pts) with lung cancer wh...