Relevance of shrinkage versus fragmented response patterns in rectal cancer.

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.

Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance.

AIMS: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival. METHODS AND RESULTS: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5-5.6] and poorer 5-year overall survival (30 versus 80% respectively, P = 0.001). CONCLUSIONS: The validation cohort confirmed these findings, although had more advanced cases (case-stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented-pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0-3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response.

Estudio comparativo de los resultados del tratamiento del carcinoma anal escamoso en los pacientes HIV positivos y negativos / Comparative study of the results of the treatment of squamous anal carcinoma in HIV positive and negative patients

Introducción: El tratamiento del carcinoma anal escamoso (CAE) en los pacientes HIV positivos resulta controvertido. Si bien las guías actuales recomiendan realizar en los pacientes con buen estado inmunológico la quimiorradioterapia (QRT) concurrente estándar, algunos autores consideran que estos pacientes presentan mayor toxicidad y peores resultados a largo plazo, por lo que requerirían un abordaje diferente. El objetivo de este trabajo es comparar los resultados del tratamiento del CAE en los pacientes VIH positivos y negativos. Diseño: Estudio retrospectivo comparativo. Pacientes y métodos: Se revisaron retrospectivamente las historias clínicas de los pacientes tratados en el Sector Coloproctología, Hospital Fernández, entre 01/2007 y 10/2018. Los del conducto anal se dividieron en: Grupo I: VIH negativos y Grupo II: VIH positivos. Se compararon variables demográficas, factores de riesgo específicos, estadificación, QRT (drogas, toxicidad y respuesta), tratamiento quirúrgico curativo/paliativo, persistencia/recurrencia y supervivencia específica y global. Resultados: Se incluyeron 28 pacientes (18 mujeres); margen: 2, conducto: 26 (Grupo I: 15. Grupo II: 11). Los VIH positivos eran en su mayoría hombres que tienen sexo con hombres vs. 100% de mujeres VIH negativas (p<0,01), más jóvenes (45,2±0,9 vs. 63,6±8; p<0,01) y tabaquistas (82% vs. 27%; p=0,005). No hubo diferencia significativa en la estadificación, aunque el Grupo II tuvo tumores con complicaciones más severas. Pudieron completar el tratamiento: Grupo I: 93%, Grupo II: 64% (p<0,05). Tuvieron respuesta completa a la QRT 13/14 (93%) pacientes del Grupo I y 3/7 (43%) del Grupo II (p<0,01). Hubo 3 recurrencias, 2 locorregionales y 1 a distancia (p=NS). Los VIH positivos requirieron más cirugías (82% vs. 27%; p<0,01). A 5 pacientes (4 del Grupo II) se les realizó una resección abdominoperineal (RAP). Tuvieron colostomía definitiva, con o sin RAP, el 46% de los pacientes, la mayoría VIH positivos (82% vs. 27%; p=0,002). En los VIH positivos el RR de mortalidad por cáncer fue 4 (IC95%: 1,01-16,5; p=0,02) y el RR de mortalidad global fue 5,45 (IC95%: 1,42-20,8; p=0,002). Tuvieron menor supervivencia, tanto global (p=0,001) como libre de enfermedad (p=0,01). Mediana de seguimiento: 27 meses (4-216).Conclusiones: Los pacientes VIH positivos con CAE se diferenciaron de los VIH negativos en una menor tasa de respuesta completa a la QRT y una mayor necesidad de tratamiento quirúrgico. Además, tuvieron una supervivencia global y libre de enfermedad significativamente menor que los VIH negativos. (AU)

INTRODUCTION: The treatment of anal squamous cell carcinoma (SCC) in HIV-positive patients is controversial. Although current guidelines recommend performing standard concurrent chemoradiotherapy (CRT) in patients with good immune status, some authors believe that these patients have greater toxicity and worse long-term results, so they would require a different approach. The purpose of this study was to compare the results of SCC treatment in HIV-positive and HIV-negative patients.DESIGN: Comparative retrospective study.PATIENTS AND METHODS: The records of patients treated in the Coloproctology Section, Hospital Fernández, between 01/2007 and 10/2018 were retrospectively reviewed. Those of the anal canal were divided into: Group I: HIV-negative and Group II: HIV-positive. Demographic variables, specific risk factors, staging, CRT (drugs, toxicity, and response), curative/palliative surgical treatment, persistence/recurrence, and cancer-specific and global survival were compared.RESULTS: 28 patients (18 women), margin: 2, conduit: 26 (Group I: 15. Group II: 11). The HIV-positive were mostly men who have sex with men (vs. 100% HIV-negative women; p<0.01), younger (45.2 ± 0.9 vs. 63.6 ± 8; p<0.01) and smokers (82% vs. 27%; p=0.005). There was no significant difference in staging, although Group II had tumors with more severe complications. Completed the treatment: Group I: 93%, Group II: 64% of patients (p<0,05). Thirteen out of 14 (93%) patients in Group I, and 3/7 (43%) patients in Group II had a complete response to CRT (p<0.01). There were 3 recurrences, 2 loco-regional and 1 distance (p=NS). HIV-positive required more surgery (82% vs. 27%; p<0.01). 5 patients (4 of Group II) underwent an abdominal-perineal resection (APR). Forty six percent of patients had permanent colostomy, with or without APR, most of them were HIV-positive (82% vs. 27%; p=0.002). In HIV-positive patients, the RR of cancer mortality was 4 (95% CI: 1.01-16.5; p=0.02) and the RR of overall mortality was 5.45 (95% CI: 1.42-20, 8; p=0.002). They also had lower overall (p=0.001) and disease-free survival (p=0.01). Median follow-up: 27 months (4 - 216).CONCLUSION: HIV-positive patients with anal SCC were different from HIV-negative patients in that they had a lower complete response rate to CRT, and a greater need for surgical treatment. They had a significantly lower overall and disease-free survival than HIV-negative patients. (AU)

Automated Information Extraction on Treatment and Prognosis for Non-Small Cell Lung Cancer Radiotherapy Patients: Clinical Study.

BACKGROUND: In outcome studies of oncology patients undergoing radiation, researchers extract valuable information from medical records generated before, during, and after radiotherapy visits, such as survival data, toxicities, and complications. Clinical studies rely heavily on these data to correlate the treatment regimen with the prognosis to develop evidence-based radiation therapy paradigms. These data are available mainly in forms of narrative texts or table formats with heterogeneous vocabularies. Manual extraction of the related information from these data can be time consuming and labor intensive, which is not ideal for large studies. OBJECTIVE: The objective of this study was to adapt the interactive information extraction platform Information and Data Extraction using Adaptive Learning (IDEAL-X) to extract treatment and prognosis data for patients with locally advanced or inoperable non-small cell lung cancer (NSCLC). METHODS: We transformed patient treatment and prognosis documents into normalized structured forms using the IDEAL-X system for easy data navigation. The adaptive learning and user-customized controlled toxicity vocabularies were applied to extract categorized treatment and prognosis data, so as to generate structured output. RESULTS: In total, we extracted data from 261 treatment and prognosis documents relating to 50 patients, with overall precision and recall more than 93% and 83%, respectively. For toxicity information extractions, which are important to study patient posttreatment side effects and quality of life, the precision and recall achieved 95.7% and 94.5% respectively. CONCLUSIONS: The IDEAL-X system is capable of extracting study data regarding NSCLC chemoradiation patients with significant accuracy and effectiveness, and therefore can be used in large-scale radiotherapy clinical data studies.

Performance of diffusion-weighted magnetic resonance imaging at 3.0T for early assessment of tumor response in locally advanced rectal cancer treated with preoperative chemoradiation therapy.

PURPOSE: The purpose of the article is to determine whether changes in apparent diffusion coefficient (ADC) values of locally advanced rectal cancer (LARC) obtained 2 weeks after the beginning of chemoradiation therapy (CRT) allow to predict treatment response and whether correlate with tumor histopathologic response. METHODS: Forty-three patients receiving CRT for LARC and 3.0T magnetic resonance imaging with diffusion-weighted sequences before treatment, 2 weeks during, and 8 weeks post the completion of CRT were included. ADC values were calculated at each time point and percentage of ADC changes at 2 weeks (ΔADC during) and 8 weeks (ΔADC post) were assessed. Data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. ADC values and ΔADCs of complete responders (CR; TRG1) and non-complete responders (non-CR; TRG 2-5) were compared. Receiver-operating characteristic curve (ROC) analysis was used to assess diagnostic accuracy of ΔADC for differentiating CR from non-CR. The correlation with TRG was investigated using Spearman's rank test. RESULTS: ΔADC during and ΔADC post were significantly higher in CR (33.9% and 57%, respectively) compared to non-CR (13.5% and 2.2%, respectively) group (p = 0.006 and p < 0.001, respectively). ROC analysis revealed the following diagnostic performances: ΔADC during: AUC 0.78 (0.08), p = 0.004, cut-off 20.6% (sensitivity 75% and specificity 76.5%); ΔADC post: AUC 0.94 (0.04), p ≤ 0.001, cut-off 22% (sensitivity 95% and specificity 82.4%). Significant moderate and good negative correlation was found between ΔADC during and ΔADC post and TRG (r = - 0.418, p = 0.007; r = - 694, p ≤ 0.001, respectively). CONCLUSION: ΔADC at 2 weeks after the beginning of CRT is a reliable tool to early assess treatment response.

Investigation of volumetric apparent diffusion coefficient histogram analysis for assessing complete response and clinical outcomes following pre-operative chemoradiation treatment for rectal carcinoma.

PURPOSE: To investigate the relationship of pre-treatment volumetric apparent diffusion coefficient (ADC) histogram parameters with post-operative histopathologic treatment response and clinical outcomes following pre-operative chemoradiation treatment (CRT) in rectal cancer. MATERIALS AND METHODS: In a Health Insurance Portability and Accountability Act compliant retrospective study, 78 rectal cancer patients treated with pre-operative CRT and rectal MRI were included. MR imaging analysis was performed using OncoTREAT (software tool). Multiple volumetric ADC histogram parameters (voxel distribution across ADC ranges, kurtosis, and skewness) were assessed. Correlation was made to post-operative pathological complete response, clinical, or radiological evidence of disease progression using the Mann-Whitney test. RESULTS: Post CRT, 8 patients showed pathologic complete response and 13 patients showed distant disease progression. Pre-treatment mean ADC was 1.2 × 10-3 mm2/s (range 0.3-1.99 × 10-3 mm2/s). Mean kurtosis measured was 0.56 (range -1 to 6; SD 1.36). Mean skewness was 0.3 (range -1 to 2; SD 0.69). Skewness had significant correlation (p value = 0.006) with disease progression. The mean rectal tumor volume was 24cc (range 1cc-134cc). Pre-treatment MRI tumor volume showed significant correlation (p value = 0.013) with pathologic complete response. Mean ADC and percentage voxels distribution against ADC ranges had no significant correlation with treatment response or disease outcomes. CONCLUSION: Volumetric ADC histogram analysis of pre-CRT rectal cancer MRI appears promising for prediction of post-CRT complete response and disease progression.