Long-Term Results of a Phase 1 Dose Escalation Trial of Ablative Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy is increasingly used for oligometastatic disease as well as palliation, but treatment protocols for nonspine bone and nodal metastases are lacking, with a wide variety of schedules applied. METHODS AND MATERIALS: A prospective dose-escalation trial was initiated, involving 90 patients, among whom 52 (58%) had primary prostate tumors, 13 had breast tumors (14%), and 25 (28%) had other primary tumor types. All visible lymph node or nonspine bone oligometastases were treated in 3 consecutive cohorts: 5 × 7.0 Gy, 3 × 10.0 Gy, or 1 × 20.0 Gy. RESULTS: Initial results revealed no dose-limiting toxicity after a median follow-up of 17.2 months. This update provides information on long-term toxicity, local failure (LF), and progression-free survival (PFS). After a median follow-up of 50 months, no new safety signals were observed. Grade 2 toxicity was 13%, 7% and 10% in the respective cohorts (P = .9), without grade 3 to 5 toxicities. LF rates were 9%, 3%, and 6% (P = .5) for the respective treatment groups, with an overall cumulative risk of LF of 7% (95% CI, 2-12) at 4 years. Median PFS was 16.5 months (95% CI, 9.8-21.5), and 4-year PFS was 21% (95% CI, 14-32). Median overall survival across groups was not reached (95% CI, 52.8 - not reached), 4-year OS was 68% (95% CI, 59-78). A subset of patients (23%) remained long-term disease-free, 37% had oligoprogressive disease at first recurrence and 40% developed polymetastatic relapse. CONCLUSIONS: The safe and effective use of dose-escalated single-fraction stereotactic body radiation therapy for bone and lymph node metastases is supported by this trial, especially considering patient-convenience and cost-effectiveness. Caution is needed when generalizing these outcomes beyond breast and prostate cancer, given their underrepresentation in our study.

The use of in-vivo dosimetry to identify head and neck cancer patients needing adaptive radiotherapy.

BACKGROUND AND PURPOSE: Head and neck cancer (HNC) patients experiencing anatomical changes during their radiotherapy (RT) course may benefit from adaptive RT (ART). We investigated the sensitivity of an electronic portal imaging device (EPID)-based in-vivo dosimetry (EIVD) system to detect patients that require ART and identified its limitations. MATERIALS AND METHODS: A retrospective study was conducted for 182 HNC patients: laryngeal cancer without elective lymph nodes (group A), postoperative RT (group B) and primary RT including elective lymph nodes (group C). The effect of anatomical changes on the dose distribution and volumetric changes was quantified. The receiver operating characteristic curve was used to obtain the optimal cut-off value for the gamma passing rate (%GP) with a dose difference of 3% and a distance to agreement of 3 mm. RESULTS: Fifty HNC patients receiving ART were analyzed: 1 in group A, 10 in group B and 39 in group C. Failed fractions (FFs) occurred in 1/1, 6/10 and 23/39 cases before ART in group A, B and C respectively. In the four cases in group B without FFs, only minor dosimetric changes were observed. One of the cases in group C without FFs had significant dosimetric changes (false negative). Three cases received ART because of clinical reasons that cannot be detected by EIVD. The optimal cut-off value for the %GP was 95%/95.2% for old/new generation machines respectively. CONCLUSION: EIVD combined with 3D imaging techniques can be synergistic in the detection of anatomical changes in HNC patients who benefit from ART.

Nonoperative versus operative approach according to the response to neoadjuvant chemoradiotherapy for rectal cancer: A prospective cohort study.

Purpose: To report on organ preservation following chemoradiotherapy (CRT) in a prospective cohort of locally advanced rectal cancer patients. Methods and materials: Fifty-two patients received CRT. MRI and 18F-FDG-PET/CT were performed prior to CRT. Response assessment was done 6 and 12 weeks after CRT using digital rectal examination, MRI, 18F-FDG-PET/CT and endoscopy. For clinical complete response or minimal residual disease, a watch-and-wait (W&W) protocol was started.Regrowth-free survival (ReFS), Total Mesorectal Excision-free disease-free survival, distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using Kaplan-Meier method. Functional outcome was compared with the Wilcoxon signed-rank test using EORTC QLQ-C30, MSKCC BFI, LARS and IIEF-5/FSFI-5 questionnaires. A previously developed prediction model performance was tested using receiver operating characteristic analysis. Results: 29/52 patients entered a W&W protocol. There was no difference in two-year DMFS (81.1 % vs 78.8 %, p = 0.82), two-year OS (96.4 % vs 100 %, p = 0.38) and two-year DFS (77.5 % vs 78.8 %, p = 0.87) between W&W patients and those who underwent surgery at 12 weeks after CRT. Two-year DMFS differed between W&W with local regrowth, W&W with sustained response and patients who had surgery (66.7 % vs 88.0 % vs 78.8 %; p = 0.04). At 6 and 12 months, W&W patients reported good QoL and bowel function. The model validation reached an AUC of 0.627. Conclusion: Good functional outcome in patients with rectal cancer allocated to surveillance after CRT needs to be balanced against potentially worse DMFS in a subset of patients without sustained clinical complete response. Reliable prediction of patients eligible for surveillance programs needs further investigation.

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights.

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.

Precision of image-guided spinal stereotactic ablative radiotherapy and impact of positioning variables.

Background and purpose: Spinal stereotactic ablative body radiotherapy (SABR) requires high precision. We evaluate the intrafraction motion during cone-beam computed tomography (CBCT) guided SABR with different immobilization techniques. Material and methods: Fifty-seven consecutive patients were treated for 62 spinal lesions with SABR with positioning corrected in six degrees of freedom. A surface monitoring system was used for patient set up and to ensure patient immobilization in 65% of patients. Intrafractional motion was defined as the difference between the last CBCT before the start of treatment and the first CT afterwards. Results: For all 194 fractions, the mean intrafractional motion was 0.1 cm (0-1.1 cm) in vertical direction, 0.1 cm (0-1.1 cm) in longitudinal direction and 0.1 cm (0-0.5 cm) in lateral direction. A mean pitch of 0.6° (0-4.3°), a roll of 0.5° (0-3.4°) and a rotational motion of 0.4° (0-3.9°) was observed. 95.5% of the translational errors and 95.4% of the rotational errors were within safety range. There was a significantly higher rotational motion for patients with arms along the body (p = 0.01) and without the use of the body mask (p = 0.05). For cervical locations a higher rotational motion was seen, although not significant (p = 0.1). The acquisition of an extra CBCT was correlated with a higher rotational (pitch) motion (p = 0 < 0.01). Conclusion: Very high precision in CBCT guided and surface-guided spinal SABR was observed in this cohort. The lowest intrafraction motion was seen in patients treated with arms above their head and a body mask. The use of IGRT with surface monitoring is an added value for patient monitoring leading to treatment interruption if necessary.

Completeness of Reporting Oligometastatic Disease Characteristics in the Literature and Influence on Oligometastatic Disease Classification Using the ESTRO/EORTC Nomenclature.

PURPOSE: There is increasing evidence for the integration of locally ablative therapy into multimodality treatment of oligometastatic disease (OMD). To support standardised data collection, analysis, and comparison, a consensus OMD classification based on fundamental disease and treatment characteristics has previously been established. This study investigated the completeness of reporting the proposed OMD characteristics in literature and evaluated whether the proposed OMD classification system can be applied to the historical data. METHODS AND MATERIALS: A systematic literature review was performed in Medline, Embase, and Cochrane, searching for prospective and retrospective studies, where stereotactic body radiation therapy was a treatment component of OMD. Reporting of the OMD characteristics as described in the European Organisation for Research and Treatment of Cancer/European Society for Radiotherapy and Oncology classification was analyzed, feasibility to retrospectively classify the proposed OMD states was investigated, and the effect of the categorization on overall survival (OS) was evaluated. RESULTS: Our study shows incomplete reporting of the proposed OMD characteristics. The most fully reported characteristic was type of involved organs (88/95 studies); history of cancer progression was the least reported (not mentioned in 50/95 studies). Retrospective OMD classification of existing literature was only possible for 7 of the 95 studies. With respect to categorization as de novo, repeat, or induced OMD, homogeneous patient cohorts were observed in 21 of the 95 studies, most frequently de novo OMD in 20 studies. Differences in OS at 2, 3, or 5 years were not statistically significant between the different states. OS was significantly influenced by primary tumor histology, with superior OS observed for prostate cancer and worst OS observed for non-small cell lung cancer. CONCLUSIONS: The largely incomplete reporting of the proposed OMD characteristics hampers a retrospective classification of existing literature. To facilitate future comparison of individual studies, as well as validation of the OMD classification, comprehensive reporting of OMD characteristics using standardised terminology is recommended, as proposed by the European Organisation for Research and Treatment of Cancer/European Society for Radiotherapy and Oncology classification system and following the European Society for Radiotherapy and Oncology/American Society for Radiation Oncology consensus.

The Dutch-Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 515 Patients and 668 Metastases.

PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). RESULTS: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. CONCLUSIONS: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

Stereotactic Ablative Radiation Therapy to All Lesions in Patients With Oligometastatic Cancers: A Phase 1 Dose-Escalation Trial.

PURPOSE: Increasing evidence suggests that patients with a limited number of metastases benefit from SABR to all lesions. However, the optimal dose and fractionation remain unknown. This is particularly true for bone and lymph node metastases. Therefore, a prospective, single-center, dose-escalation trial was initiated. METHODS: Dose-Escalation trial of STereotactic ablative body RadiOtherapY for non-spine bone and lymph node metastases (DESTROY) was an open-label phase 1 trial evaluating SABR to nonspine bone and lymph node lesions in patients with up to 3 metastases. Patients with European Cooperative Oncology Group performance status ≤1, an estimated life expectancy of at least 6 months, and histologically confirmed nonhematological malignancy were eligible. Three SABR fractionation regimens, ie, 5 fractions of 7.0 Gy versus 3 fractions of 10.0 Gy versus a single fraction of 20.0 Gy, were applied in 3 consecutive patient cohorts. The rate of ≥grade 3 toxicity, scored according to the Common Toxicity Criteria for Adverse Events v. 4.03, up to 6 months after SABR, was the primary endpoint. The trial was registered on clinicaltrials.gov (NCT03486431). RESULTS: Between July 2017 and December 2018, 90 patients were enrolled. In total 101 metastases were treated. No ≥grade 3 toxicity was observed in any of the enrolled patients (95% CI 0.0%-12.3% for the first cohort with 28 analyzable patients; 95% CI 0.0%-11.6% for the second and third cohort with 30 analyzable patients each). Treatment-related grade 2 toxicities occurred in 4 out of 30 versus 2 out of 30 versus 2 out of 30 patients for the 5, 3 and 1 fraction schedule, respectively. Actuarial local control rate at 12 months was 94.5%. CONCLUSION: All 3 treatment schedules were feasible and effective with remarkably low toxicity rates and high local control rates. From a patient and resource point of view, the single-fraction schedule is undoubtedly most convenient.

Patient-derived organoids as individual patient models for chemoradiation response prediction in gastrointestinal malignancies.

Chemoradiotherapy (CRT) is an important treatment modality for specific gastrointestinal (GI) cancers, as it has been shown to improve clinical outcomes. Recent developments in the neoadjuvant setting such as wait-and-see strategies for rectal as well as for esophageal cancers have even proven that CRT might be an effective organ-sparing treatment. However, due to molecular heterogeneity, only a subset of patients will show a complete response to CRT, which addresses the need for an individualized treatment approach. In recent years, the demand for more physiologically relevant predictive in vitro models has fostered the development of patient-derived tumor organoids. In this review, we describe the current treatment options for patients with GI cancers who are treated with (neo)adjuvant CRT. Furthermore, we provide an in-depth discussion of the organoid technology in the context of predicting CRT response for GI cancers as well as possible challenges for clinical implementation.

Can medical imaging identify the histopathological growth patterns of liver metastases?

The histopathological growth patterns (HGPs) of liver metastases of colorectal cancer and of several other tumor types predict outcome of patients in multiple studies. The HGPs of liver metastases have a prognostic but also a predictive value with one of the growth patterns, the replacement growth pattern, related to resistance to systemic treatment. Given that the HGP can only be assessed in a reliable manner when a surgical resection of the metastasis has been performed, this biomarker cannot be exploited to the full. For example, HGPs can at this moment, not be used to decide whether patients with liver metastatic breast or colorectal cancer will benefit or not from locoregional treatment, such as surgery or radiotherapy, and from peri-operative systemic treatment. In this review we highlight studies that suggest that the HGPs of liver metastases can be identified by medical imaging. Although still to be confirmed by a prospective multicenter approach, some studies indeed achieve a high accuracy in predicting the HGPs by applying radiomic algorithms on CT- or MR-images of liver metastases. This is an important step towards a treatment planning of patients with liver metastatic cancer that takes into account the biology and the progression kinetics of the metastases.

Outcome and toxicity of hypofractionated image-guided SABR for spinal oligometastases.

BACKGROUND: To investigate progression free survival (PFS), local control (LC) and overall survival (OS) outcomes for patients treated with spine hypofractionated stereotactic ablative radiotherapy (SABR) and to evaluate possible predictors of rapid progression in view of a correct patient selection for this potentially curative SABR. MATERIALS AND METHODS: A cohort of 59 patients with spinal metastases were treated with SABR. Patient selection criteria were the following: histologically proven diagnosis of a solid tumor, a World Health Organization (WHO) score ≤ 2, life expectancy > 6 months, Spinal Instability Neoplastic Score (SINS) ≤ 12 points and presenting with radically treated oligometastatic disease (≤5 lesions) or stable polymetastatic disease with an oligoprogressive lesion. RESULTS: From March 2015 to June 2019, 59 patients were treated with Linac-based SABR to 64 spinal metastases with a median follow-up of 55 months. SABR was standard delivered every other day in 3 to 10 fractions with median prescription dose of 27 Gy (range 21-49 Gy).The 1-,2- and 5-year PFS was 98%, 85% and 75% for all patients. OS at 5 years for all patients was 92%. Metachronous lesions (p < 0.01; HR = 7.1) and oligometastatic (vs. oligoprogressive) lesions (p = 0.02; HR = 0.3) were associated with higher PFS in uni- and multivariate Cox regression analysis. No significant predictors in multivariate analysis were demonstrated for rapid progressors.Vertebral compression fractures developed de novo in 6.3% (4/64) of cases. The median time to fracture was 11 months (range 7-15) after treatment. No other adverse events ≥ 3 grade were observed. CONCLUSIONS: Tumor control and toxicity after high-dose hypofractionated SABR was evaluated in patients with spinal oligometastases. High rates of efficacy and minimal toxicity were demonstrated. Oligometastatic patients with metachronous spinal metastases seem to benefit the most from SABR.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET).

BACKGROUND: Bone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic. METHODS: This is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24-48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode. DISCUSSION: If a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures. TRIAL REGISTRATION: The Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov ( NCT03831243 ) on February 5th 2019.

Moderate dose escalation with volumetric modulated arc therapy improves outcome in rectal cancer.

BACKGROUND: Locally advanced rectal cancer is frequently treated with a long course of preoperative chemoradiotherapy. We investigated the effect of moderate dose escalation with volumetric modulated arc therapy (VMAT) up to 50 Gy in 25 fractions compared to 3D conformal radiotherapy (3D-CRT) to 45 Gy in 25 fractions in rectal cancer patients. Dose-volume parameters, acute toxicity, and complete response rates were compared. MATERIAL AND METHODS: For both groups, 65 patients were selected from our database through availability. Dose-volume parameters and acute toxicity data were compared using a Mann-Whitney U-test. Univariate and multivariate analyses correcting for tumor and nodal stage, distance to the mesorectal fascia and interval to surgery were used to compare complete response rates. RESULTS: Lower mean doses to the small and large bowel were observed in the VMAT group compared to the 3D-CRT group (21 Gy vs. 29 Gy [p < .001] and 26 Gy vs. 30 Gy [p = .002], respectively). Similar beneficial dose-volume parameters were observed for the bladder, sacrum and femoral heads. Furthermore, patients receiving VMAT experienced significantly less diarrhea, flatulence, non-infective cystitis, urinary frequency, dermatitis, and fatigue. In univariate analysis, a significant increase in complete response rate after moderate dose escalation with VMAT was observed (34% vs. 15%, p = .015). However, this did not remain significant when corrected for tumor and nodal stage, distance to the mesorectal fascia, and interval to surgery. CONCLUSIONS: Moderate dose escalation with VMAT resulted in superior dose-volume parameters compared to 3D-CRT, translating into lower acute toxicity. Additionally, improved tumor response after VMAT up to 50 Gy might contribute to a higher percentage of patients achieving a complete response.

Quantitative imaging outperforms molecular markers when predicting response to chemoradiotherapy for rectal cancer.

BACKGROUND AND PURPOSE: To explore the integration of imaging and molecular data for response prediction to chemoradiotherapy (CRT) for rectal cancer. MATERIAL AND METHODS: Eighty-five rectal cancer patients underwent preoperative CRT. 18F-FDG PET/CT and diffusion-weighted imaging (DWI) were acquired before (TP1) and during CRT (TP2) and prior to surgery (TP3). Inflammatory cytokines and gene expression were analysed. Tumour response was defined as ypT0-1N0. Multivariate models were built combining the obtained parameters. Final models were calculated on the data combination with the highest AUC. RESULTS: Twenty-two patients (26%) achieved ypT0-1N0 response. 18F-FDG PET/CT had worse predictive performance than DWI and T2-volumetry (AUC 0.61±0.04, 0.72±0.03, and 0.72±0.02, respectively). Combining all imaging parameters increased the AUC to 0.81±0.03. Adding cytokines or gene expression did not improve the AUC (AUC of 0.72±0.06 and 0.79±0.04 respectively). Final models combining 18F-FDG PET/CT, DWI, and T2-weighted volumetry at all TPs and using only TP1 and TP3, allowed ypT0-1N0 prediction with a 75% sensitivity, 94% specificity and PPV of 80%. CONCLUSIONS: Combining 18F-FDG PET/CT, DWI, and T2-weighted MRI volumetry obtained before CRT and prior to surgery may help physicians in selecting rectal cancer patients for organ-preservation.

International consensus guidelines on Clinical Target Volume delineation in rectal cancer.

INTRODUCTION: The delineation of Clinical Target Volume (CTV) is a critical step in radiotherapy. Several guidelines suggest different subvolumes and anatomical boundaries in rectal cancer (RC), potentially leading to a misunderstanding in the CTV definition. International consensus guidelines (CG) are needed to improve uniformity in RC CTV delineation. MATERIAL AND METHODS: The 7 radiation oncologist experts defined a roadmap to produce RC CG. Step 1: revision of the published guidelines. Step 2: selection of RC cases with different clinical stages. Step 3: delineation of cases using Falcon following previously published guidelines. Step 4: meeting in person to discuss the initial delineation outcome, followed by a CTV proposal based on revised and if needed, adapted anatomical boundaries. Step 5: peer review of the agreed consensus. Step 6: peer review meeting to validate the final outcome. Step 7: completion of RC delineation atlases. RESULTS: A new ontology of structure sets was defined and the related table of anatomical boundaries was generated. The major modifications were about the lateral lymph nodes and the ischio-rectal fossa delineation. Seven RC cases were made available online as consultation atlases. CONCLUSION: The definition of international CG for RC delineation endorsed by international experts might support a future homogeneous comparison between clinical trial outcomes.

Survival among clinical stage I-III rectal cancer patients treated with different preoperative treatments: A population-based comparison.

BACKGROUND: Radical resection is regarded as the cornerstone of rectal cancer treatment. Preoperative (chemo)radiotherapy and adjuvant chemotherapy are often administered. This population-based study compares the survival in clinical stage I-III rectal cancer patients who received either preoperative radiotherapy, preoperative chemoradiotherapy or no preoperative therapy. As secondary research questions, the association of type of radical resection and adjuvant chemotherapy on survival is also investigated. METHODS: Patients diagnosed between January 2006 and December 2011 with stage I-III rectal adenocarcinoma were retrieved from the Belgian Cancer Registry database. Multivariable Cox proportional hazards regression models were applied to evaluate the association of preoperative treatment, type of radical resection and use of adjuvant chemotherapy with survival, adjusting for the baseline characteristics age, gender, WHO performance status and clinical stage. RESULTS: A total of 5173 rectal cancer patients were identified. Preoperative treatment was as follows: none in 1354 (26.2%), radiotherapy in 797 (15.4%) and chemoradiotherapy in 3022 (58.4%) patients. The patient group who did not receive preoperative therapy or radiotherapy followed by radical resection had a lower observed survival compared to the patient group receiving preoperative chemoradiotherapy. The patient groups who underwent abdominoperineal excision and those receiving adjuvant chemotherapy had a worse observed survival compared to the patient group treated with sphincter-sparing surgery and no adjuvant therapy respectively. These effects were age-dependent. Multivariable analysis demonstrated similar findings for the observed survival conditional on surviving the first year since surgery. CONCLUSION: In this population-based study among clinical stage I-III rectal cancer patients treated with radical resection, a superior observed survival was noticed in the patient group receiving preoperative chemoradiotherapy compared to the patients groups receiving no or preoperative radiotherapy only, adjusting for case mix, type of radical resection and adjuvant chemotherapy. Additionally, higher adjusted observed survival was also detected for the patient groups with sphincter-sparing surgery or no adjuvant chemotherapy.

Do refined consensus guidelines improve the uniformity of clinical target volume delineation for rectal cancer? Results of a national review project.

In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice.

Can clinical factors be used as a selection tool for an organ-preserving strategy in rectal cancer?

BACKGROUND: Rectal cancer patients who achieve a good response to chemoradiotherapy (CRT), may be offered less invasive surgery or even no surgery at all. Implementation of such a policy, however, requires precise patient selection. This study identifies pretreatment clinical factors that are associated with pathological complete response (pCR) and ypT0-1N0 and evaluates their performance as a selection tool for organ-preserving strategies. MATERIAL AND METHODS: Patients with rectal cancer treated with CRT and total mesorectal excision between January 2000 and December 2014 were retrospectively included. Following clinical characteristics were extracted from the medical files: age, gender, body mass index, ASA score, cT-stage, cN-stage, distance from the anal verge, pretreatment carcinoembryonic antigen (CEA), pretreatment hemoglobin and distance from the mesorectal fascia. Univariable and multivariable binary logistic regression models were used to predict pCR and ypT0-1N0. The discriminative ability of the prediction models was evaluated by receiver operating characteristic analysis. RESULTS: A total of 620 patients were included of whom 120 experienced a pCR (19%) and 170 patients achieved ypT0-1N0 response (27%). A low pretreatment CEA, a high pretreatment hemoglobin and a high cN-stage were associated with pCR in multivariable analysis. A low pretreatment CEA, a low cT-stage and a high cN-stage were associated with ypT0-1N0. After cross validation, the area under the curve for the pCR and ypT0-1N0 prediction model equaled 0.609 and 0.632, respectively. CONCLUSION: Despite their statistical significance, the value of pretreatment clinical variables in the prediction of pCR and ypT0-1N0 is very limited. To safely select patients for organ preservation, other strategies need to be explored.

Which Patients With Rectal Cancer Do Not Need Radiotherapy?

According to current guidelines, the standard treatment for locally advanced rectal cancer patients is preoperative (chemo)radiotherapy followed by total mesorectal excision surgery and adjuvant chemotherapy. Improvements in surgical techniques, imaging modalities, chemotherapy regimens, and radiotherapy delivery have reduced local recurrence rates to less than 10%. The current challenge in rectal cancer treatment lies in the prevention of distant metastases, which still occur in more than 25% of the patients. The decrease in local recurrence rates, the need for more effective systemic treatments, and the increased awareness of treatment-induced toxicity raise the question as to whether a more selective use of radiotherapy is advocated.