Organ preservation following short-course radiotherapy for rectal cancer.

BACKGROUND: Non-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients. METHODS: Patients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated. RESULTS: Of 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups. CONCLUSION: In this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy.

Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial.

BACKGROUND AND PURPOSE: Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 × 5 Gy surgery within one week (SRT), 5 × 5 Gy with surgery after 4-8 weeks, and 2 Gy × 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. MATERIAL AND METHODS: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). RESULTS: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. CONCLUSION: SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 × 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.

Changes in Clinical Practice Reduce the Rate of Anastomotic Leakage After Colorectal Resections.

BACKGROUND: Anastomotic leakage is a serious clinical problem after colorectal resections and is associated with a significantly increased length of stay, morbidity and mortality. The aim of the present study was to evaluate the effect of changes in clinical practice on anastomotic leakage rate after colorectal resections. METHODS: Retrospective cohort study based on prospectively collected data. All 894 patients with primary anastomosis after colorectal resection at a tertiary referral center between 2006 and 2013 were analyzed. Changes in clinical practice aiming at reducing the rate of anastomotic leakages were introduced in January 2010 and were characterized by exclusion of perioperative nonsteroidal anti-inflammatory drugs, introduction of intra-operative goal-directed fluid therapy and avoidance of primary anastomoses in emergency resections. The study population was divided into two groups, one treated before and one after the introduction of changes in clinical practice. Groups were compared regarding patient characteristics and incidence of anastomotic leakage. RESULTS: The cumulative incidence of anastomotic leakage after colorectal resections decreased from 10.0% (41 of 409) to 4.5% (22 of 485) after changing clinical practice, relative risk 0.45 (95% CI 0.27-0.75, p = 0.002). The adjusted odds ratio was 0.45 (0.26-0.78, p = 0.004). A separate analysis showed a decrease after colon resections from 9.1% (23 of 252) to 4.5% (14 of 310), relative risk 0.49 (0.26-0.94, p = 0.039), and from 11.5% (18 of 157) to 4.6% (8 of 175) after rectal resections, relative risk 0.40 (0.18-0.89, p = 0.024). CONCLUSION: Implementing a structured change of clinical practice can significantly reduce the anastomotic leakage rate after colorectal resections. TRIAL REGISTRATION: Clinical trial registration number: ACTRN12617001497392.

Assessment of testicular dose during preoperative radiotherapy for rectal cancer.

BACKGROUND: Radiotherapy (RT) for rectal cancer can have adverse effects on testicular function resulting in azoospermia and low testosterone levels. Variability of testicular dose (TD) due to differences in position of testes has been assessed with scrotal dosimeters and resulted in substantial variability of delivered TD. The aim of this study was to estimate planned and delivered TD using a treatment planning system (TPS). METHODS: In 101 men treated with RT for rectal cancer the cumulative mean TD (mTD) was calculated by TPS based on plan-computed tomography (CT) to evaluate the effect of different predictors on planned TD. The delivered TD was estimated by TPS based on repeated cone-beam CTs in 32 of 101 men to assess within-person variability of planned and delivered TD in a longitudinal analysis. RESULTS: The median planned mTD for short course RT was 0.57 Gy (range 0.06-14.37 Gy) and 0.81 Gy (range 0.36-10.80 Gy) for long course RT. The median planned mTD was similar to the median delivered mTD in the 32 men analysed over the entire course of RT (p=0.84). The mTD did not change significantly over time of planning and delivering RT. The variation in proximity between testes and planning target volume (PTV) was related to within-person variability of mTD in men on the 50th and 75th percentile of mTD and as expected the absolute difference between planned and delivered mTD increased with higher mTD. CONCLUSION: Testicular doses calculated based on plan-CT are an accurate estimation of delivered TD based on repeated cone beam (CB)CT. The within-person variability of TD is related to variation in proximity between testes and PTV in men with moderate to high TD.

Low anterior resection syndrome and quality of life: an international multicenter study.

BACKGROUND: An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to 90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome. OBJECTIVE: The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer. DESIGN: The study was designed as an international cross-sectional study involving 5 centers in 4 European countries. PATIENTS: All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery. INTERVENTIONS: The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30. MAIN OUTCOME MEASURES: Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea. RESULTS: A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation. LIMITATIONS: The cross-sectional design prevents an evaluation of causality. CONCLUSIONS: The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.

International validation of the low anterior resection syndrome score.

OBJECTIVE: The aims of this study were to investigate the convergent and discriminative validity and reliability of the low anterior resection syndrome (LARS) score in an international setting. BACKGROUND: The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal cancer surgery. The score is intended to be commonly used in international research and clinical practice in the future. Therefore, a thorough validation in an international setting is of utmost importance. METHODS: The LARS score was translated using methods in keeping with current international recommendations. A total of 801 patients operated for rectal cancer in Sweden, Spain, Germany, and Denmark completed the LARS score questionnaire, including an anchor question assessing the impact of bowel function on quality of life. A subgroup of 218 patients completed the LARS score twice. Data were analyzed per country. RESULTS: The LARS score has demonstrated a high convergent validity in terms of a high correlation between LARS score and quality of life (P < 0.001). Sensitivity ranged from 67.7% to 88.3% and specificity from 58.1% to 86.3%. The LARS score was able to discriminate between groups of patients differing with regard to radiotherapy, surgery, and age (P < 0.05). The score also demonstrated high reliability at test-retest with narrow limits of agreement and no statistically significant difference between scores at the first and second test. CONCLUSIONS: The Swedish, Spanish, German, and Danish versions of the LARS score have proven to be valid and reliable tools for measuring LARS in European rectal cancer patients.