The treatment of locally advanced rectal cancer (LARC) has evolved during the last decades, but recurrence remains a problem. Circulating tumor DNA (ctDNA) may result in an individualized treatment ...approach with improved survival and quality of life, but diverging results impede further development. In this systematic review, we addressed the quality of reporting and its impact on the interpretation of ctDNA results. We performed a systematic literature search using subject headings and search terms related to ctDNA and rectal cancer. The Quality of Prognostic Studies (QUIPS) tool was used to assess bias. Nine studies, with substantial heterogeneity, were included in the analysis. Three out of nine articles had moderate or high risk of bias. No association was found between treatment response and ctDNA status at baseline. There was a negative association between ctDNA positivity at baseline, before and after surgery and survival. The ctDNA status may be of importance to the long-term prognosis, but the area of research is new and is short of dedicated studies. There is an obvious need for standardization in ctDNA research, and the issue should be addressed in future research.
Surgery is standard treatment for rectal cancer, but neoadjuvant chemoradiation therapy (CRT) may result in clinical complete response (cCR) in select patients, allowing for nonsurgical management ...(NSM). Prospective studies of NSM strategies are sparse, however, and long-term data on quality of life (QoL) are limited. We conducted a single-arm phase 2 trial of high-dose CRT for NSM of distal rectal cancer; we report secondary long-term patient-reported outcomes (PROs), local regrowth, and overall survival in patients managed nonsurgically.
Fifty-one patients with resectable, T2 or T3, N0-N1, low adenocarcinoma received 65 Gy (intensity modulated radiation therapy, brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, magnetic resonance imaging, biopsy) were referred for observation and followed closely with clinical examination, endoscopy, positron emission tomography/computed tomography, and PROs for 5 years. Overall colorectal cancer-specific QoL and specific symptom scores were evaluated at baseline and in follow-up and compared between time points. Local regrowth was estimated using cumulative incidence and overall survival using Kaplan-Meier estimates.
Forty patients achieved cCR after treatment; 29 were in follow-up at 24 months, 21 at 36 months, and 20 at 60 months. PRO questionnaire completion rates were 90% at 24 months, 100% at 36 months, and 85% at 60 months for patients still in follow-up. Average QoL score did not differ between baseline (median 11.1) and 24 months (13.7), 48 months (11.1), or 60 months (6.9). Only rectal bleeding deteriorated from baseline, with bowel- and bladder-related symptom scores otherwise unchanged in follow-up. At median follow-up of 5.0 years, local regrowth rate and overall survival were 31% (95% confidence interval, 15%-47%) and 85% (95% confidence interval, 75%-97%), respectively.
Long-term follow-up after NSM of distal rectal cancer showed excellent general colorectal cancer QoL and local symptom scores. Our study results indicate that high-dose CRT followed by organ preservation might be an alternative to standard treatment.
Abstract only
3611
Background: Surgery is standard treatment for rectal cancer, but neoadjuvant chemoradiotherapy (CRT) may result in clinical complete response (cCR) in selected patients, allowing ...for non-surgical management (NSM). Prospective studies of NSM strategies are sparse however, and long-term data on quality of life (QoL) are limited. We conducted a single-arm phase II trial of high-dose CRT for NSM of distal rectal cancer; we report secondary long-term patient-reported outcomes (PROs), local regrowth and overall survival (OS) in patients managed non-surgically. Methods: Fifty-one patients with resectable, T2 or T3, N0–N1, low adenocarcinoma received 65Gy (IMRT, brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, MRI, biopsy) were referred for observation, and followed closely with clinical examinations, endoscopies, PET-CTs, and PROs for 5 years. Overall colorectal cancer specific QoL and specific symptom scores were compared between timepoints using paired Wilcoxon tests. Local regrowth was estimated using cumulative incidence; overall survival using Kaplan-Meier estimates. Results: Forty patients achieved cCR after treatment; 28 were in follow-up at 24m, 21 at 36m, 18 at 60m. Patients left the trial due to local tumor regrowth (n=12), distant metastases (n=3), new primary cancers (n=6) and loss to follow-up (n=1). Average QoL score did not differ between baseline (median 11.1) and 24m (13.7), 48m (11.1,) or 60m (6.9). See Table for individual scores; only rectal bleeding deteriorated from baseline (significantly worse at 24m). At median follow-up of 5.0 years, local regrowth rate and OS were 31% (95 CI 15%-47%) and 85% (95 CI 75%-97%), respectively. Conclusions: Long term follow-up after NSM of early rectal cancer showed excellent general colorectal cancer QoL and local symptom scores. (NCT00952926). EORTC QLQ – CR 29. Proportion reporting ‘quite a bit’ or ‘very much’ on symptom scales. Clinical trial information: NCT00952926. Table: see text
No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore ...biopsy (IS
) was recently suggested in a preliminary study.
This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to IS
. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between IS
and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence.
Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with IS
High, IS
Intermediate, and IS
Low, respectively (hazard ratio HR; Low
High, 6.51; 95% CI, 1.99 to 21.28; log-rank
= .0004). IS
was also significantly associated with disease-free survival (log-rank
= .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, IS
was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR IS
High
Low, 6.93; 95% CI, 2.08 to 23.15;
= .0017). The addition of IS
to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR.
The IS
is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.
3517
Background: The WW strategy for patients with rectal cancer who achieved a clinical complete response (cCR) after neoadjuvant therapy (nT) allows to avoid major resection and the associated ...morbidity and mortality. Standardized criteria to select and monitor WW patients, including biomarkers predicting recurrence after nT, are lacking. The prognostic impact of the immune infiltrate in colorectal cancers is now demonstrated and has been implemented into clinics through the Immunoscore, the first standardized digital-pathology-based assay, recommended by academic institutions. We evidenced that an Immunoscore adapted to biopsies (IS
B
) performed at diagnosis, predicts the response to nT and the risk of recurrence after nT. Its clinical utility was suggested in a test cohort of WW patients (El Sissy et al., Clin Cancer Res 2020). The aim of this study was to confirm the ability of the IS
B
to predict clinical outcomes, improve patients’ eligibility for the WW strategy, and optimize a follow-up schedule. Methods: A total of 304 WW patients from 10 centers across 7 countries were included. Tumor biopsies before treatment were immunostained for CD3+ and CD8+ T-cells and converted to IS
B
using the pre-defined cut-off. The primary endpoint was time-to-recurrence (TTR). Secondary endpoint was disease-free-survival (DFS). As immune response originates in draining lymph nodes, signs of immune activation were carried out in lymph nodes of additional patients managed by radical surgery with complete pathological response (pCR; n = 12) or non-pCR (n = 12) by 3' RNA-Seq and immunofluorescence technologies. Results: High-IS
B
patients presented with the lowest risk of recurrence after WW. 5-year recurrence-free rates were 97% (92%-100%), 61% (49%-76%), and 56% (44%-73%) with IS
B
High, Intermediate, and Low, respectively (HR Low-vs-High = 14.3, 95% CI 1.8-100). In patients with cCR after nT (n = 209), High-IS
B
showed a significant association with prolonged TTR and DFS (Logrank P = 0.005 and P = 0.006, respectively). When IS
B
was evaluated as a continuous variable, the risk of recurrence was increasing along with decreasing IS
B
(Wald tests, all P < 0.005). In multivariate analyses, IS
B
was independent of age, sex, location, and cTNM stage and was the single parameter correlated with TTR (HR IS
B
High-vs-Low = 0.08, 95% CI 0.01-0.6; P = 0.015) and DFS (P = 0.013). Unlike for patients with cCR, no difference according to IS
B
was observed for those with incomplete response (n = 41) or treated with brachytherapy (n = 34). Finally, intranodal signs of T-cell and B-cell activation were only evidenced in patients with pCR. Conclusions: IS
B
provides a reliable biomarker to predict clinical outcomes, improve eligibility, and optimize patients’ follow-up. Intranodal T-cell and B-cell activation further supports the immune benefit of both organ and lymph node preservation.
This commentary attempts to discuss the required standardization of circulating tumor DNA (ctDNA) analyses and thereby improve the clinical validity of ctDNA monitoring in the metastatic setting of ...solid tumors.
Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local ...and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit. Indeed, each therapy can cause its own side-effects, which may worsen by a combination of treatments resulting in long-term poor QoL. In LARC, QoL has become even more essential with the increasing incidence of rectal cancer in young individuals. Herein, we analyzed the value of the Immunoscore-Biopsy (performed on tumor biopsy at diagnosis) in predicting outcomes, alone or in association with clinical and imaging data, for each therapy used in LARC.
represents a multiploid and facultative apomictic system of widely distributed mountain populations. We used flow cytometry to determine genome size, ploidy level, and reproduction mode variation of ...the Balkan populations, supplemented by analysis of nuclear microsatellites in order to address: (i) geographic distribution and variation of cytotypes among the populations; (ii) variation of reproduction mode and the frequency of sexuality; (iii) pathways of endosperm formation among the sampled polyploids and their endosperm balance requirements; (iv) genotypic diversity and geographic distribution of clonal lineages of polyploids. The prevalence of apomictic tetraploid cytotype followed by sexual diploids and extremely rare triploids was demonstrated. This prevalence of tetraploids affected the populations' structure composed from clonal genotypes with varying proportions. The co-occurrence of diploids and tetraploids generated higher cytotype, reproductive mode, and genotypic diversity, but mixed-ploidy sites were extremely rare. The endosperm imbalance facilitates the development and the occurrence of intermediate triploids in mixed-ploidy populations, but also different tetraploid lineages elsewhere with unbalanced endosperm. All these results showed that the South European populations of
have higher levels of cytotype and reproductive diversity compared to the Central European ones. Therefore, the South European populations can be considered as a potential reservoir of regional and global diversity for this species.
The aim of the research was to examine morphological status of children with cerebral palsy of primary school age, and to determine whether significant differences exist in relation to children with ...no disability. The research composes of total sample of 60 examinees. The first subsample of 30 examinees was made of children with cerebral palsy of average chronological age of 10-14 years, of which 50% were female examinees and 50% of male examinees. The second subsample is made of children with no disabilities aged 10-14 years, of equable sex as in the first subsample of examinees, chosen by random choice method (N=30). Measuring of anthropometric characteristics was done by method of International biological program, for which instruments of standard construction were used, previously calibrated and daily controlled before use. Research data were processed by method of parametric and non-parametric statistics. For the aim of check-up of set research, a ttest was applied for independent sample of examinees. Research results have shown that, in relation to skin folds, children with cerebral palsy have, in relation to children with no disability, accomplished significant difference on variables "Upper arm skin fold" (t=-2, 67; p≤0,01), "Forearm skin fold" (t=-3,11; p≤0,01), "Thigh skin fold" (t=-5,37; p≤0,01),"Double chin skin fold" (t=-3,98; p≤0,01), "Back skin fold" (t=-3,06; p≤0,01) and "Stomach skin fold" (t=-3,49; p≤0,01). On basis of gained research results, it can be concluded that children with no disability in relation to children with cerebral palsy are on level of statistical importance taller, heavier, but children with cerebral palsy in relation to children of typical development have higher values of sub dermal adipose tissue.
Bakgrund: Sjuksköterskans arbete präglas av att kunna arbeta preventivt gällande de olikalivsstilsfaktorerna. Det preventiva arbetet anses vara en viktig faktor när det gällerhälsoutvecklingen hos ...Sveriges befolkning. Syfte: Syftet med studien var att beskrivasjuksköterskans undervisande arbete då det gäller frågor kring livsstil i arbetet med patienter som vårdas för hjärt- och kärl sjukdomar. Metod: Empirisk observationsstudie utifrån en kvalitativansats och enkätstudie utifrån en kvantitativ ansats. Resultatet analyserades med hjälp av en manifest innehållsanalys. Resultat: De rådgivande samtalen fungerade överlag bra. Vissa undantag föreföll dock. Under observationerna observerades det att alkohol var ett av de ämnen som diskuterades minst, då det uppgavs vara ett känsligt ämne. Samtalsstrategierna överensstämde med litteraturen om hur ett rådgivande samtal bör utformas. Slutsats: Resultatet tyder på att små förändringar bör ske vid de rådgivande samtalen. En öppnare inställning kring alkohol och rökning bör tillämpas då dessa är två av de störst bidragande faktorerna gällande hjärt- och kärl sjukdomar och många andra sjukdomstillstånd.
Background: A nurse's work is characterized by working in a preventive manor concerning the different lifestyle factors.The preventive work is considered to be an important factor in the health development of the Swedish population. Objective: The purpose of the study was to describe the nurse's educational work concerning questions about lifestyle habits for patients who are treated for cardiovasculardiseases. Method: Empirical observational study based on a qualitative approach and a survey based on a quantitative approach. The results were analyzed by using a manifest content analysis.Results: Overall, the consultative talks was working fine. Some exceptions appeared, however.During observations, it was noticed that alcohol was one of the subjects that was least frequently mentioned, as it was stated to be a sensitive topic. Call strategies were consistent with the literature and the recommendations for how consultative talks should be designed. Conclusions: The results suggest that small changes should be made at the consultative talks. A more open attitude should be applied about alcohol and smoking . This because these are two of the greatest contributing factors for cardiovascular disease and many other diseases.
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