Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts.

BACKGROUND: In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. METHODS: Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. RESULTS: Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). CONCLUSION: Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancer-results from the RAPIDO trial.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial. PATIENTS AND METHODS: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression. RESULTS: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1. CONCLUSIONS: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

The Long and the Short of it: the Role of Short-course Radiotherapy in the Neoadjuvant Management of Rectal Cancer.

Total mesorectal excision is the cornerstone of treatment for rectal cancer. Multiple randomised trials have shown a reduction in local recurrence rates with the addition of preoperative radiotherapy, either as a 1-week hypofractionated short-course (SCRT) or a conventionally fractionated long-course (LCRT) schedule with concurrent chemotherapy. There is also increasing interest in the addition of neoadjuvant chemotherapy to radiotherapy with the aim of improving disease-free survival. The relative use of SCRT and LCRT varies considerably across the world. This is reflected in, and is probably driven in part by, disparity between international guideline recommendations. In addition, different approaches to treatment may exist both between and within countries, with variation related to patient, disease and treatment centre and financial factors. In this review, we will specifically focus on the use of SCRT for the treatment of rectal cancer. We will discuss the literature base and current guidelines, highlighting the challenges and controversies in clinical application of this evidence. We will also discuss potential future applications of SCRT, including its role in optimisation and intensification of treatment for rectal cancer.

MRI cT1-2 rectal cancer staging accuracy: a population-based study.

BACKGROUND: Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS). METHODS: Patients with cT1-2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value. RESULTS: Of 7382 registered patients with cT1-2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1-2 N1 respectively. CONCLUSION: This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1-2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.

ANTECEDENTES: Una adecuada estadificación mediante resonancia magnética nuclear (RMN) de los cánceres de recto en estadios precoces es esencial para la toma de decisiones en una era en la existen diferentes opciones de tratamiento preservadoras del recto. El objetivo de este estudio de base poblacional fue determinar la precisión de la estadificación mediante RMN del cáncer de recto precoz en la práctica diaria, ya sea combinada o no con la ecografía endorectal (endorectal ultrasound, ERUS). MÉTODOS: Los pacientes con cáncer de recto en estadio cT1-2 que se sometieron a resección local o resección total del mesorrecto (total mesorectal excision, TME) sin (quimio) radioterapia neoadyuvante fueron seleccionados a partir del registro auditado ColoRectal holandés, entre el 1 de enero de 2011 y el 31 de diciembre de 2018. La precisión de las imágenes se expresó como sensibilidad, especificidad y valores predictivos positivo y negativo (positive- and negative predicting value, PPV / NPV). RESULTADOS: De un total de 7.382 pacientes registrados con cáncer de recto en estadio cT1-2, se incluyeron 5.539 pacientes (5.288 solamente RMN, 251 RMN + ERUS; 1.059 cT1 y 4.480 cT2). Los pacientes pT1 fueron sobreestadificados cuando se utilizó únicamente la RMN en un 54,7% de los casos (792/1.448) y cuando se combinó RMN y ERUS en un 31,0% (36/116). La infraestadificación de pT2 ocurrió en un 8,2% (197/2.388) y en un 27,9% (31/111), respectivamente. La RMN utilizada como única prueba sobreestadificó los casos pN0 en el 17,3% (570/3.303) y el VPP del estadio cN0 fue del 76,3% (2.733/3.583). De los 834 pacientes con estadio pT1N0, potencialmente adecuado para la resección local, 253 pacientes (30,3%) se clasificaron correctamente como cT1N0, y 484 (58,8%) y 97 (11,6%) pacientes se sobreestadificaron como cT2N0 y cT1-2N1, respectivamente. CONCLUSIÓN: Este estudio de base poblacional holandés en pacientes que se sometieron a una resección local o a cirugía TME por cáncer de recto cT1-2 con estadificación preoperatoria mediante RMN, muestra una considerable sobreestadificación, lo que indica las debilidades y oportunidades en las estrategias de preservación del recto.

Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique.

PURPOSE: To compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI). METHODS: Between 2011 and 2016 women ≥60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 × 23.3 Gy) or photon EB-APBI (10 × 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year. RESULTS: HRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS). CONCLUSIONS: EB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels.

Robust contour propagation using deep learning and image registration for online adaptive proton therapy of prostate cancer.

PURPOSE: To develop and validate a robust and accurate registration pipeline for automatic contour propagation for online adaptive Intensity-Modulated Proton Therapy (IMPT) of prostate cancer using elastix software and deep learning. METHODS: A three-dimensional (3D) Convolutional Neural Network was trained for automatic bladder segmentation of the computed tomography (CT) scans. The automatic bladder segmentation alongside the computed tomography (CT) scan is jointly optimized to add explicit knowledge about the underlying anatomy to the registration algorithm. We included three datasets from different institutes and CT manufacturers. The first was used for training and testing the ConvNet, where the second and the third were used for evaluation of the proposed pipeline. The system performance was quantified geometrically using the dice similarity coefficient (DSC), the mean surface distance (MSD), and the 95% Hausdorff distance (HD). The propagated contours were validated clinically through generating the associated IMPT plans and compare it with the IMPT plans based on the manual delineations. Propagated contours were considered clinically acceptable if their treatment plans met the dosimetric coverage constraints on the manual contours. RESULTS: The bladder segmentation network achieved a DSC of 88% and 82% on the test datasets. The proposed registration pipeline achieved a MSD of 1.29 ± 0.39, 1.48 ± 1.16, and 1.49 ± 0.44 mm for the prostate, seminal vesicles, and lymph nodes, respectively, on the second dataset and a MSD of 2.31 ± 1.92 and 1.76 ± 1.39 mm for the prostate and seminal vesicles on the third dataset. The automatically propagated contours met the dose coverage constraints in 86%, 91%, and 99% of the cases for the prostate, seminal vesicles, and lymph nodes, respectively. A Conservative Success Rate (CSR) of 80% was obtained, compared to 65% when only using intensity-based registration. CONCLUSION: The proposed registration pipeline obtained highly promising results for generating treatment plans adapted to the daily anatomy. With 80% of the automatically generated treatment plans directly usable without manual correction, a substantial improvement in system robustness was reached compared to a previous approach. The proposed method therefore facilitates more precise proton therapy of prostate cancer, potentially leading to fewer treatment-related adverse side effects.

Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients.

BACKGROUND AND PURPOSE: We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients. MATERIALS AND METHODS: Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0-10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires. RESULTS: In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00). CONCLUSION: Acute toxicity after IORT and EB-APBI treatment is acceptable.

Evaluation of clinical and endoscopic toxicity after external beam radiotherapy and endorectal brachytherapy in elderly patients with rectal cancer treated in the HERBERT study.

INTRODUCTION: The HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity. MATERIAL AND METHODS: A brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 × 3 Gy) followed by three weekly HDREBT applications (5-8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon's signed rank test, paired t-test and Spearman's correlation were used. RESULTS: Patient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and ≥3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12-18 months after treatment. CONCLUSION: For elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated.

Clinical outcomes of definitive chemoradiotherapy using carboplatin and paclitaxel in esophageal cancer.

Patients with nonmetastatic esophageal cancer not suitable for surgery can be treated with definitive chemoradiotherapy with curative intent. The purpose of this retrospective study is to evaluate the clinical outcomes of definitive chemoradiotherapy using carboplatin and paclitaxel. Medical records were reviewed of patients treated for nonmetastatic squamous cell or adenocarcinoma of the esophagus between January 2009 and December 2013 in two collaborating institutes. Treatment consisted of external beam radiotherapy (28 fractions of 1.8 Gy) and 6 weekly courses of carboplatin (AUC = 2) and paclitaxel (50 mg/m2). Data on survival, progression, toxicity, and effect on dysphagia were recorded. Sixty-six patients were included. Median overall survival (OS) was 13.1 months (95% CI 4.7-21.5 months) and a 2-year OS was 30% (95% CI 18%-42%). At 2 years, 26% of patients developed local progression (95% CI 15%-37%) and 49% developed distant metastases (95% CI 36%-64%). Acute toxicity grade ≥3 was observed in 47% of patients. Late adverse events grade ≥3 were seen in 20%, mostly esophageal stenoses. Of patients with available data 3 months after treatment, 70% had relief of dysphagia. Definitive chemoradiotherapy led to a median OS of 13 months. Toxicity was common, mostly due to hematological toxicity. Given the relatively short median survival, an adequate selection of patients for this intensive treatment is required.

Changes in nationwide use of preoperative radiotherapy for rectal cancer after revision of the national colorectal cancer guideline.

BACKGROUND: The rate of preoperative radiotherapy (RT) for rectal cancer in the Netherlands has been the highest among European countries. Revision of the national guideline on colorectal cancer, officially published in 2014, specifically focussed on the indication for RT and MRI criteria to evaluate mesorectal lymph nodes. The objective of this study was to evaluate implementation of the revised guideline using a national audit. METHODS: Data of the Dutch Surgical Colorectal Audit (DSCA) between 2009 and 2014 were used to evaluate RT use and RT regimen for relevant subgroups of cM0 rectal cancer patients, as well as accuracy of pre-operative MRI. RESULTS: 14,018 patients were included for analysis. Overall RT use in cT1-4N0-2M0 stage ranged from 81.4% to 84.2% between 2009 and 2013, and decreased to 64.4% in 2014. The absolute decrease in RT use from 2013 to 2014 for cT1N0, cT2N0 and cT3N0 stage was 32.8%, 43.5% and 31.6%, respectively. Short course RT with delayed surgery was used as an alternative to chemoradiotherapy up to 2013 in 30.6% of patients over 80 years, and in 12.1% of patients with an ASA score >2; these percentages increased to 45.8% and 19.9% in 2014, respectively. Specificity of MRI for N-stage decreased from 82.9% in 2009 to 62.9% in 2013, with an increase to 73.2% in 2014. CONCLUSION: The revised national guideline on colorectal cancer was rapidly implemented in the Netherlands with a substantial decrease in RT use for low risk resectable rectal cancer, and increased specificity of MRI for N-staging.

Oncologist, patient, and companion questions during pretreatment consultations about adjuvant cancer treatment: a shared decision-making perspective.

OBJECTIVES: To assess the occurrence of questions that foster shared decision making, in particular cancer patients' understanding of treatment decisions and oncologists' understanding of patients' priorities, during consultations in which preference-sensitive decisions are discussed. Specifically, (a) regarding patient understanding, do oncologists ask about patients' preexisting knowledge, information preferences, and understanding and do patients and companions ask about the disease and treatment, and (b) regarding patient priorities, do oncologists ask about patients' treatment- and decision-related preferences and do patients and companions ask about the decision? METHODS: Audiotaped pretreatment consultations of 100 cancer patients with 32 oncologists about (neo)adjuvant treatment were coded and analyzed to document question type, topic, and initiative. RESULTS: The oncologists ascertained prior knowledge in 50 patients, asked 24 patients about preferred (probability) information, and invited questions from 56 patients. The oncologists asked 32 patients about treatment preferences and/or for consent. Respectively, one-third and one-fifth of patients and companions asked about treatment benefits compared with three-quarters of them who asked about treatment harms and/or procedures. CONCLUSIONS: It would be helpful to patients if oncologists more often assessed patients' existing knowledge to tailor their information provision. Also, patients could receive treatment recommendations that better fit their personal situation if oncologists collected information on patients' views about treatments. Moreover, by educating patients to ask about treatment alternatives, benefits, and harms, patients may gain a better understanding of the choice they have.

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015.

Meta-analysis of oncological outcomes after local excision of pT1-2 rectal cancer requiring adjuvant (chemo)radiotherapy or completion surgery.

BACKGROUND: Completion total mesorectal excision (TME) is advised for high-risk early (pT1/pT2) rectal cancer following transanal removal. The main objective of this meta-analysis was to determine oncological outcomes of adjuvant (chemo)radiotherapy as a rectum-preserving alternative to completion TME. METHODS: A literature search using PubMed, Embase and the Cochrane Library was performed in February 2015. Studies had to include at least ten patients with pT1/pT2 adenocarcinomas that were removed transanally and followed by either adjuvant chemoradiotherapy or completion surgery. A weighted average of the logit proportions was determined for the pooled analyses of subgroups according to treatment modality and pT category. RESULTS: In total, 14 studies comprising 405 patients treated with adjuvant (chemo)radiotherapy and seven studies comprising 130 patients treated with completion TME were included. Owing to heterogeneity it was not possible to compare the two strategies directly. However, the weighted average local recurrence rate for locally excised pT1/pT2 rectal cancer treated with adjuvant (chemo)radiotherapy was 14 (95 per cent c.i. 11 to 18) per cent, and 7 (4 to 14) per cent following completion TME. The weighted averages for distance recurrence were 9 (6 to 14) and 9 (5 to 16) per cent respectively. Weighted averages for local recurrence rate after adjuvant chemo(radiotherapy) and completion TME for pT1 were 10 (4 to 21) and 6 (3 to 15) per cent respectively. Corresponding averages for pT2 were 15 (11 to 21) and 10 (4 to 22) per cent respectively. CONCLUSION: A higher recurrence rate after transanal excision and adjuvant (chemo)radiotherapy must be balanced against the morbidity and mortality associated with mesorectal excision. A reasonable approach is close follow-up and salvage mesorectal surgery as needed.

The beneficial local and abscopal effect of splenic irradiation in frail patients with chronic lymphocytic leukaemia.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a common haematological malignancy that mainly occurs in the elderly population. Patients frequently have comorbidities compromising the use of old and new systemic therapies. METHODS AND RESULTS: We report the prevalence of comorbidities in patients with CLL as present in the southern region of the Netherlands Cancer Registry. Comorbid conditions were present in 67% of the male and 63% of the female patients, and became more common with increasing age. Furthermore, we describe the beneficial local and abscopal effects of splenic irradiation in four patients with CLL who were not suitable for systemic chemoimmunotherapy because of severe comorbidities, or who were unwilling to undergo systemic therapy. CONCLUSION: Our results show that, although an old tool, splenic irradiation should not be forgotten as a potentially effective palliative treatment option in frail patients with symptomatic CLL.

The EORTC QLQ-CR29 quality of life questionnaire for colorectal cancer: validation of the Dutch version.

PURPOSE: To validate the Dutch version of the EORTC QLQ-CR29 quality of life questionnaire for colorectal cancer. METHODS: We translated and pilot-tested the original questionnaire in the Netherlands, following EORTC guidelines. We assessed factor structure, reliability and construct validity in different samples of patients from four hospitals. RESULTS: Of 296 patients, 236 (80 %) returned the questionnaire, and 27 out of 48 patients returned the retest questionnaire. In addition to the original three scales, we found a reliable bowel functioning scale (α = 0.80), reducing the number of individual items by five. Two of the other scales had sufficient to good reliability (urinary frequency, α = 0.71, original α = 0.75, body image α = 0.80, original α = 0.84), the third, blood and mucus in stool, only moderate (α = 0.56, original α = 0.69). Item functioning was sufficient to excellent for all but two items (urinary incontinence and dysuria). Construct validity was similar to that in earlier studies. CONCLUSION: We found a very satisfactory scale for bowel problems, in patients both with and without stoma. The body image and urinary incontinence scales were reliable, and construct validity was sufficient. We suggest the questionnaire to be adapted to decrease the number of individual items, improve the scales, and therefore increase reliability of the entire questionnaire.