BACKGROUND:Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative ...organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome.
OBJECTIVE:The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group).
DESIGN:This was a matched controlled study.
SETTINGS:This study was conducted at multiple centers.
PATIENTS:The study population consisted of 2 groups41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years.
MAIN OUTCOME MEASURES:Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score).
RESULTS:The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function.
LIMITATIONS:This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study with a limited number of patients and with quality-of-life measurements on nonpredefined and variable intervals after surgery.
CONCLUSIONS:After a successful watch-and-wait approach, the quality of life was better than after chemoradiation and surgery on several domains. However, chemoradiation therapy on its own is not without long-term side effects, because one-third of the watch-and-wait patients experienced major low anterior resection syndrome symptoms, compared with 66.7% of the patients in the total mesorectal excision group. See Video Abstract at http://links.lww.com/DCR/A395.
The epidemiology of colorectal cancer (CRC) has changed rapidly over the years. The aim of this study was to assess the trends in incidence, treatment, and relative survival (RS) of patients ...diagnosed with CRC in the Netherlands between 2000 and 2021.
2 75667 patients diagnosed with CRC between 2000 and 2021 were included from the Netherlands Cancer Registry. Analyses were stratified for disease extent (localised: T1-3N0M0; regional: T4N0M0/T1-4N1-2M0; distant: T1-4N0-2M1) and localisation (colon; rectum). Trends were assessed with joinpoint regression.
CRC incidence increased until the mid-2010s but decreased strongly thereafter to rates comparable with the early 2000s. Amongst other trend changes, local excision rates increased for patients with localised colon (2021: 13.6 %) and rectal cancer (2021: 34.9 %). Moreover, primary tumour resection became less common in patients with distant colon (2000–2021: 60.9–12.5 %) or rectal cancer (2000–2021: 47.8–6.9 %), while local treatment of metastases rates increased. Five-year RS improved continuously for localised and regional colon (97.7 % and 72.0 % in 2017, respectively) and rectal cancer (95.2 % and 76.3 % in 2017, respectively). The rate of anti-cancer treatments decreased in distant colon (2010–2021: 80.3 % to 67.2 %; p < 0.001) and rectal cancer (2011–2021: 86.0 % to 77.0 %; p < 0.001). The improvement of five-year RS stagnated for distant colon (2010–2017: 11.2 % to 11.9 %; average percentage of change APC: 2.1, 95 % confidence interval CI: −7.6, 4.7) and rectal cancer (2009–2017: 12.7 % to 15.6 %; APC: 1.4, 95 % CI: −19.1, 5.5).
Major changes in the incidence and treatment of CRC between 2000 and 2021 were identified and quantified. Five-year RS increased continuously for patients with localised and regional CRC, but stagnated for patients with distant CRC, likely caused by decreased rates of anti-cancer treatment in this group.
•Clinical practice for colorectal cancer (CRC) has changed vastly in recent years.•The incidence of CRC has decreased rapidly since population screening.•Rates of anti-cancer treatment decreased for distant CRC since approximately 2010.•Relative survival increased for localised and regional CRC during the study.•For distant CRC, relative survival did not increase since approximately 2010.
•Late dose-volume effects of radiotherapy on the anorectal function were studied in rectal cancer patients.•33.3% of the patients had major LARS (Low Anterior Resection Syndrome).•Clustering and urge ...incontinence were the most common complaints.•Trends towards higher Vaizey and LARS scores after higher doses to the anal sphincter complex were observed.
To assess the long-term anorectal function in rectal cancer patients following a watch-and-wait policy after chemoradiotherapy and to investigate the dose–volume effects of radiotherapy on the anorectal function.
Thirty-three patients with primary rectal cancer who were treated with chemoradiotherapy and a watch-and-wait policy with minimum follow-up of 2 years were included. We assessed the anorectal function using anorectal manometry and patient reported outcomes (Vaizey and LARS score). Dose–volume histograms were calculated for the rectum and anal sphincter complex, and associations between the dose–volume parameters and anorectal function were assessed.
Dmean to the rectum and anal sphincter complex was 50.5 Gy and 44.7 Gy, respectively. After a median follow-up of 38 (range 23–116) months, 33.3% of the patients reported major LARS. Mean LARS score was 23.4 ± 11.3 and mean Vaizey score was 4.3 ± 4.1. The most frequent complaints were clustering of defaecation and faecal urgency. Trends towards a higher Vaizey and LARS score after higher anal sphincter complex dose were observed, although these associations were not statistically significant.
This is the first study to investigate the late dose-volume effects of radiotherapy specifically on the anorectal function in rectal cancer patients. One-third of the patients had major LARS and the most frequent reported complaints were clustering and faecal urgency. Additionally, we observed trends towards worse long-term anorectal function after higher anal sphincter complex radiotherapy dose. However, this should be evaluated on a larger scale. Future efforts to minimise the dose to the sphincters could possibly reduce the impact of radiotherapy on the anorectal function.
Berbée, M., Fu, Q., Boerma, M., Wang, J., Kumar, K. S. and Hauer-Jensen, M. γ-Tocotrienol Ameliorates Intestinal Radiation Injury and Reduces Vascular Oxidative Stress after Total-Body Irradiation by ...an HMG-CoA Reductase-Dependent Mechanism. Radiat. Res. 171, 596–605 (2009). Analogs of vitamin E (tocols) are under development as radioprophylactic agents because of their high efficacy and lack of toxicity. Gamma-tocotrienol (GT3) is of particular interest because, in addition to being an antioxidant, it also inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and accumulates to greater extent in endothelial cells than other tocols. We addressed in vivo whether HMG-CoA reductase inhibition contributes to the radioprotection conferred by GT3. Groups of mice were treated with vehicle, mevalonate (the product of the reaction catalyzed by HMG-CoA reductase), GT3 alone or GT3 in combination with mevalonate. Lethality and standard parameters of injury to the hematopoietic, intestinal and vascular/endothelial systems were assessed after exposure to total-body irradiation. GT3 improved postirradiation survival and decreased radiation-induced vascular oxidative stress, an effect that was reversible by mevalonate. GT3 also enhanced hematopoietic recovery, reduced intestinal radiation injury, and accelerated the recovery of soluble markers of endothelial function. These parameters were not reversed by mevalonate co-administration. Our data confirm GT3's radioprophylactic properties against hematopoietic injury and, for the first time, demonstrate benefits in terms of protection against gastrointestinal and vascular injury. The radioprotective efficacy of GT3 against vascular injury is related to its properties as an HMG-CoA reductase inhibitor.
Objective
To investigate whether quantifying local tumour heterogeneity has added benefit compared to global tumour features to predict response to chemoradiotherapy using pre-treatment ...multiparametric PET and MRI data.
Methods
Sixty-one locally advanced rectal cancer patients treated with chemoradiotherapy and staged at baseline with MRI and FDG-PET/CT were retrospectively analyzed. Whole-tumour volumes were segmented on the MRI and PET/CT scans from which global tumour features (T2W
volume
/T2W
entropy
/ADC
mean
/SUV
mean
/TLG/CT
mean-HU
) and local texture features (histogram features derived from local entropy/mean/standard deviation maps) were calculated. These respective feature sets were combined with clinical baseline parameters (e.g. age/gender/TN-stage) to build multivariable prediction models to predict a good (Mandard TRG1-2) versus poor (Mandard TRG3-5) response to chemoradiotherapy. Leave-one-out cross-validation (LOOCV) with bootstrapping was performed to estimate performance in an ‘independent’ dataset.
Results
When using only imaging features, local texture features showed an AUC = 0.81 versus AUC = 0.74 for global tumour features. After internal cross-validation (LOOCV), AUC to predict a good response was the highest for the combination of clinical baseline variables + global tumour features (AUC = 0.83), compared to AUC = 0.79 for baseline + local texture and AUC = 0.76 for all combined (baseline + global + local texture).
Conclusion
In imaging-based prediction models, local texture analysis has potential added value compared to global tumour features to predict response. However, when combined with clinical baseline parameters such as cTN-stage, the added value of local texture analysis appears to be limited. The overall performance to predict response when combining baseline variables with quantitative imaging parameters is promising and warrants further research.
Key Points
•
Quantification of local tumour texture on pre-therapy FDG-PET/CT and MRI has potential added value compared to global tumour features to predict response to chemoradiotherapy in rectal cancer.
•
However, when combined with clinical baseline parameters such as cTN-stage, the added value of local texture over global tumour features is limited.
•
Predictive performance of our optimal model—combining clinical baseline variables with global quantitative tumour features—was encouraging (AUC 0.83), warranting further research in this direction on a larger scale.
Objectives
To explore the value of multiparametric MRI combined with FDG-PET/CT to identify well-responding rectal cancer patients before the start of neoadjuvant chemoradiation.
Methods
Sixty-one ...locally advanced rectal cancer patients who underwent a baseline FDG-PET/CT and MRI (T2W + DWI) and received long-course neoadjuvant chemoradiotherapy were retrospectively analysed. Tumours were delineated on MRI and PET/CT from which the following quantitative parameters were calculated: T2W volume and entropy, ADC mean and entropy, CT density (mean-HU), SUV maximum and mean, metabolic tumour volume (MTV
42%
) and total lesion glycolysis (TLG). These features, together with sex, age, mrTN-stage (“baseline parameters”) and the CRT-surgery interval were analysed using multivariable stepwise logistic regression. Outcome was a good (TRG 1–2) versus poor histopathological response. Performance (AUC) to predict response was compared for different combinations of baseline ± quantitative imaging parameters and performance in an ‘independent’ dataset was estimated using bootstrapped leave-one-out cross-validation (LOOCV).
Results
The optimal multivariable prediction model consisted of a combination of baseline + quantitative imaging parameters and included mrT-stage (OR 0.004,
p
< 0.001), T2W-signal entropy (OR 7.81,
p
= 0.0079) and T2W volume (OR 1.028,
p
= 0.0389) as the selected predictors. AUC in the study dataset was 0.88 and 0.83 after LOOCV. No PET/CT features were selected as predictors.
Conclusions
A multivariable model incorporating mrT-stage and quantitative parameters from baseline MRI can aid in identifying well-responding patients before the start of treatment. Addition of FDG-PET/CT is not beneficial.
Key Points
•
A multivariable model incorporating the mrT-stage and quantitative features derived from baseline MRI can aid in identifying well-responding patients before the start of neoadjuvant chemoradiotherapy
.
•
mrT-stage was the strongest predictor in the model and was complemented by the tumour volume and signal entropy calculated from T2W-MRI
.
•
Adding quantitative features derived from pre-treatment PET/CT or DWI did not contribute to the model’s predictive performance
.
Background
The presence of lymph node metastasis (LNmets) is a poor prognostic factor in oesophageal cancer (OeC) patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery. ...Tumour regression grade (TRG) in LNmets has been suggested as a predictor for survival. The aim of this study was to investigate whether TRG in LNmets is related to their location within the radiotherapy (RT) field.
Methods
Histopathological TRG was retrospectively classified in 2565 lymph nodes (LNs) from 117 OeC patients treated with nCRT and surgery as: (A) no tumour, no signs of regression; (B) tumour without regression; (C) viable tumour and regression; and (D) complete response. Multivariate survival analysis was used to investigate the relationship between LN location within the RT field, pathological TRG of the LN and TRG of the primary tumour.
Results
In 63 (54%) patients, viable tumour cells or signs of regression were seen in 264 (10.2%) LNs which were classified as TRG-B (
n
= 56), C (
n
= 104) or D (
n
= 104) LNs. 73% of B, C and D LNs were located within the RT field. There was a trend towards a relationship between LN response and anatomical LN location with respect to the RT field (
p
= 0.052). Multivariate analysis showed that only the presence of LNmets within the RT field with TRG-B is related to poor overall survival.
Conclusion
Patients have the best survival if all LNmets show tumour regression, even if LNmets are located outside the RT field. Response in LNmets to nCRT is heterogeneous which warrants further studies to better understand underlying mechanisms.
Abstract Purpose To test the hypothesis that cardiac comorbidity before the start of radiotherapy (RT) is associated with an increased risk of radiation-induced lung toxicity (RILT) in lung cancer ...patients. Material and methods A retrospective analysis was performed of a prospective cohort of 259 patients with locoregional lung cancer treated with definitive radio(chemo)therapy between 2007 and 2011 (ClinicalTrials.gov Identifiers: NCT00572325 and NCT00573040). We defined RILT as dyspnea CTCv.3.0 grade ⩾2 within 6 months after RT, and cardiac comorbidity as a recorded treatment of a cardiac pathology at a cardiology department. Univariate and multivariate analyses, as well as external validation, were performed. The model-performance measure was the area under the receiver operating characteristic curve (AUC). Results Prior to RT, 75/259 (28.9%) patients had cardiac comorbidity, 44% of whom (33/75) developed RILT. The odds ratio of developing RILT for patients with cardiac comorbidity was 2.58 ( p < 0.01). The cross-validated AUC of a model with cardiac comorbidity, tumor location, forced expiratory volume in 1 s, sequential chemotherapy and pretreatment dyspnea score was 0.72 ( p < 0.001) on the training set, and 0.67 ( p < 0.001) on the validation set. Conclusion Cardiac comorbidity is an important risk factor for developing RILT after definite radio(chemo)therapy of lung cancer patients.
PURPOSE OF REVIEWTo give an overview of promising novel agents under development for the prevention and reduction of gastrointestinal radiation injury.
RECENT FINDINGSCurrently, several novel agents ...are being tested as drugs to prevent or reduce gastrointestinal radiation injury. These drugs may not only prevent injury, but also mitigate toxicity, that is, reduce injury after radiation exposure has occurred. Promising novel agents include the somatostatin analogue SOM230, growth factors, agents acting on the toll-like receptor 5 pathway, endothelial protectants, and the vitamin E analogue γ-tocotrienol.
SUMMARYGastrointestinal radiation injury is the most important dose-limiting factor during radiotherapy of the abdomen or pelvis. It may severely affect the quality of life both during radiotherapy treatment and in cancer survivors. To date, there are no agents that can prevent or reduce intestinal radiation injury. Hence, there is an urgent need for the development of novel drugs to ameliorate intestinal toxicity during and after radiotherapy. This review summarizes the several agents that have been shown to reduce intestinal radiation injury in animals. Further research is needed to investigate their safety and efficacy in patients receiving radiotherapy for abdominal or pelvic tumours.
Purpose Rectal toxicity remains a major threat to quality of life of patients, who receive brachytherapy to the abdominal pelvic area. Estimating the risk of toxicity development is essential to ...maximize therapeutic benefit without impairing rectal function. This study aimed to abstract and evaluate studies, which have developed prediction models for rectal toxicity after brachytherapy (BT) in patients with pelvic cancers. Material and methods To identify relevant studies since 1995, MEDLINE database was searched on August 31, 2021, using terms related to “pelvic cancers”, “brachytherapy”, “prediction models”, and “rectal toxicity”. Papers were excluded if model specifications were not reported. Risk of bias was assessed using prediction model risk of bias assessment tool. Results Thirty models (n = 16 cervical cancer, n = 13 prostate cancer, and n = 1 rectal cancer), including 60 distinct predictors were published. Rectal toxicity varied significantly between studies (median, 25.4% for cervix, and median, 8.8% for prostate cancer). High-, low-, and pulsed-dose-rate BT were applied in 15 (50%), 13 (43%), and 1 (3%) studies, respectively. Most common predictors that retained in final models were age (n = 5, 17%), EBRT (n = 5, 17%), V100% rectum (BT) (n = 5, 17%), and dose at rectal point (n = 3, 10%). None of the studies were considered to be at low-risk of bias due to deficiencies in the analysis domain. Conclusions Existing models have limited clinical application due to poor quality of methodology. The following key issues should be considered in future studies: 1) Measuring patient-reported outcomes to address underestimation of true frequencies of rectal toxicity events; 2) Giving higher priority to reliable dose-volume parameters; 3) Avoiding overfitting by considering an event per candidate predictor rate ≥ 20; 4) Calculating detailed performance measures.
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