Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes.

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates. Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Coverage of Lateral Lymph Nodes in Rectal Cancer Patients with Routine Radiation Therapy Practice and Associated Locoregional Recurrence Rates.

PURPOSE: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for the occurrence of ipsilateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiation therapy practice in the Netherlands and associated LLR rates. METHODS AND MATERIALS: Patients with a primary tumor ≤8 cm of the anorectal junction, cT3-4 stage, and at least 1 internal iliac or obturator LLN with short axis ≥5 mm who received neoadjuvant (chemo)radiation therapy, were selected from a national, cross-sectional study of patients with rectal cancer treated in the Netherlands in 2016. Magnetic resonance images and radiation therapy treatment plans were reviewed regarding segmented LLNs as gross tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiation therapy dose. RESULTS: A total of 223 out of 3057 patients with at least 1 LLN ≥5 mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received ≥95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared with those inside (4.0% vs 12.5%, P = .092) or when receiving <95% versus ≥95% of the planned radiation therapy dose (7.1% vs 11.3%, P = .843), respectively. Two of 7 patients who received a dose escalation of 60 Gy developed an LLR (4-year LLR rate of 28.6%). CONCLUSIONS: This evaluation of routine radiation therapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further.

Patient- and physician-reported radiation-induced toxicity of short-course radiotherapy with a prolonged interval to surgery for rectal cancer.

AIM: A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. METHOD: Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. RESULTS: Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. CONCLUSION: During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

Pre-treatment visualization of predicted radiation-induced acute alopecia in brain tumour patients.

BACKGROUND AND PURPOSE: Temporary alopecia is a common side-effect in brain tumour patients receiving cranial radiotherapy with a significant psychological burden for the affected patient. The purpose of this study was to generate a method in our treatment planning system (TPS) to visualize the expected radiation-induced alopecia 4 weeks after treatment, in order to inform the patients thereupon before the start of radiotherapy. MATERIAL AND METHODS: A pilot study was conducted in ten patients receiving hypo- (HF) or conventionally fractionated (CF) photon beam Volumetric Modulated Arc Therapy (VMAT) for an intracranial lesion. Dose calculations were correlated to visible alopecia four weeks after the end of treatment to create a structure predictive of alopecia in our TPS. These alopecia structures for both fractionation schedules were validated in two cohorts of 69 HF and 78 CF patients undergoing radiotherapy between 2016 and 2019. RESULTS: In the pilot cohort, a total physical dose of 4 Gy for HF and 12.6 Gy for CF radiotherapy were found to be predictive of alopecia 4 weeks after treatment. Applying these doses to our validation cohort, we found an accurate prediction of alopecia in 59/69 (86%) HF and 73/78 (96%) CF patients. For the total patient group of 147 patients, the predicted amount of alopecia was accurate in 90% of the cases. All inaccurate predictions overestimated the expected extent of alopecia. CONCLUSION: The presented straightforward method to visualize predicted alopecia 4 weeks after treatment has proven to predict the extent alopecia highly accurate in the vast majority of patients. Sharing these results with the patients pre-treatment may result in stress reduction before cranial irradiation.

Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study).

PURPOSE: To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS: Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS: Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively (P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively (P = .15). CONCLUSION: In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.

Deciphering the glioblastoma phenotype by computed tomography radiomics.

INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary brain tumour which has, despite extensive treatment, a median overall survival of 15 months. Radiomics is the high-throughput extraction of large amounts of image features from radiographic images, which allows capturing the tumour phenotype in 3D and in a non-invasive way. In this study we assess the prognostic value of CT radiomics for overall survival in patients with a GBM. MATERIALS AND METHODS: Clinical data and pre-treatment CT images were obtained from 218 patients diagnosed with a GBM via biopsy who underwent radiotherapy +/- temozolomide between 2004 and 2015 treated at three independent institutes (n = 93, 62 and 63). A clinical prognostic score (CPS), a simple radiomics model consisting of volume based score (VPS), a complex radiomics prognostic score (RPS) and a combined clinical and radiomics (C + R)PS model were developed. The population was divided into three risk groups for each prognostic score and respective Kaplan-Meier curves were generated. RESULTS: Patient characteristics were broadly comparable. Clinically significant differences were observed with regards to radiation dose, tumour volume and performance status between datasets. Image acquisition parameters differed between institutes. The cross-validated c-indices were moderately discriminative and for the CPS ranged from 0.63 to 0.65; the VPS c-indices ranged between 0.52 and 0.61; the RPS c-indices ranged from 0.57 to 0.64 and the combined clinical and radiomics model resulted in c-indices of 0.59-0.71. CONCLUSION: In this study clinical and CT radiomics features were used to predict OS in GBM. Discrimination between low-, middle- and high-risk patients based on the combined clinical and radiomics model was comparable to previous MRI-based models.

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.

PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.

SOURCE: Prediction Models for Overall Survival in Patients With Metastatic and Potentially Curable Esophageal and Gastric Cancer.

BACKGROUND: Personalized prediction of treatment outcomes can aid patients with cancer when deciding on treatment options. Existing prediction models for esophageal and gastric cancer, however, have mostly been developed for survival prediction after surgery (ie, when treatment has already been completed). Furthermore, prediction models for patients with metastatic cancer are scarce. The aim of this study was to develop prediction models of overall survival at diagnosis for patients with potentially curable and metastatic esophageal and gastric cancer (the SOURCE study). METHODS: Data from 13,080 patients with esophageal or gastric cancer diagnosed in 2015 through 2018 were retrieved from the prospective Netherlands Cancer Registry. Four Cox proportional hazards regression models were created for patients with potentially curable and metastatic esophageal or gastric cancer. Predictors, including treatment type, were selected using the Akaike information criterion. The models were validated with temporal cross-validation on their C-index and calibration. RESULTS: The validated model's C-index was 0.78 for potentially curable gastric cancer and 0.80 for potentially curable esophageal cancer. For the metastatic models, the c-indices were 0.72 and 0.73 for esophageal and gastric cancer, respectively. The 95% confidence interval of the calibration intercepts and slopes contain the values 0 and 1, respectively. CONCLUSIONS: The SOURCE prediction models show fair to good c-indices and an overall good calibration. The models are the first in esophageal and gastric cancer to predict survival at diagnosis for a variety of treatments. Future research is needed to demonstrate their value for shared decision-making in clinical practice.

Changes in hospital variation in the probability of receiving treatment with curative intent for esophageal and gastric cancer.

BACKGROUND: Previous studies describe a large variation in the proportion of patients undergoing treatment with curative intent for esophageal (EC) and gastric cancer (GC). Since centralization of surgical care was initiated and more awareness regarding hospital practice variation was potentially present, we hypothesized that hospital practice variation for potentially curable EC and GC patients changed over time. METHODS: Patients with potentially curable EC (n = 10,115) or GC (n = 3988) diagnosed between 2012-2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to analyze the differences in the probability of treatment with curative intent between hospitals of diagnosis over time, comparing 2012-2014 with 2015-2017. Relative survival (RS) between hospitals with different probabilities of treatment with curative intent were compared. RESULTS: The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis for EC was 45-95 % in 2012-2014 and 54-89 % in 2015-2017, and for GC 52-100 % and 45-100 %. The adjusted variation declined for EC with Odds Ratios ranging from 0.50 to 1.72 between centers in the first period to 0.70-1.44 in the second period (p < 0.001) and did not change for GC (Odds Ratios ranging from 0.78 to 1.23 to 0.82-1.23, (p = 1.00)). A higher probability of treatment with curative intent was associated with a better survival for both malignancies. CONCLUSION: Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC. A low probability of receiving curative treatment remained associated with worse survival.

Patient-reported outcomes after external beam radiotherapy versus brachytherapy for palliation of dysphagia in esophageal cancer: A matched comparison of two prospective trials.

BACKGROUND AND PURPOSE: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy. MATERIALS AND METHODS: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIREC-trial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires. RESULTS: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss. CONCLUSION: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines.

Short-Course External Beam Radiotherapy Versus Brachytherapy for Palliation of Dysphagia in Esophageal Cancer: A Matched Comparison of Two Prospective Trials.

INTRODUCTION: Short-course external beam radiotherapy (EBRT) and intraluminal brachytherapy are both accepted treatments for the palliation of dysphagia in patients with incurable esophageal cancer. We compared the effects of both treatments from two prospective studies. METHODS: We performed a multicenter prospective cohort study of patients with metastasized or otherwise incurable esophageal cancer requiring palliation of dysphagia from September 2016 to March 2019. Patients were treated with EBRT in five fractions of 4 Gy. Data were compared with all patients treated with a single brachytherapy dose of 12 Gy in the SIREC (Stent or Intraluminal Radiotherapy for inoperable Esophageal Cancer) trial, both between the original cohorts and between 1:1 propensity score-matched cohorts. The primary end point was an improvement of dysphagia at 3 months without reintervention. The secondary end points included toxicity and time-to-effect. RESULTS: A total of 115 patients treated with EBRT and 93 patients who underwent brachytherapy were eligible for analysis. In the original cohorts, dysphagia improved after EBRT in 79% of patients compared with 64% after brachytherapy (p = 0.058). Propensity score matching resulted in 69 patients in each cohort well-balanced at baseline. Improvement of dysphagia was observed in 83% after EBRT versus 64% after brachytherapy (p = 0.048). In responding patients, improvement of dysphagia at 2 weeks was observed in 67% after EBRT compared with 35% after brachytherapy, and the maximum effect was reached after 4 weeks in 55% and 33%, respectively. Severe toxicity occurred in 3% of patients after EBRT compared with 13% after brachytherapy. CONCLUSIONS: Short-course EBRT appears at least as effective as brachytherapy in the palliation of dysphagia in patients with esophageal cancer.

A national study to assess outcomes of definitive chemoradiation regimens in proximal esophageal cancer.

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens.Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model.Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p = .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p = .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups.Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.

Radiotherapy quality assurance for mesorectum treatment planning within the multi-center phase II STAR-TReC trial: Dutch results.

BACKGROUND: The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer. METHODS: Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary. RESULTS: All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers. CONCLUSIONS: Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning. TRIAL REGISTRATION: The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

Patient-specific finite element computer models improve fracture risk assessments in cancer patients with femoral bone metastases compared to clinical guidelines.

PURPOSE: To determine whether patient-specific finite element (FE) computer models are better at assessing fracture risk for femoral bone metastases compared to clinical assessments based on axial cortical involvement on conventional radiographs, as described in current clinical guidelines. METHODS: Forty-five patients with 50 femoral bone metastases, who were treated with palliative radiotherapy for pain, were included (64% single fraction (8Gy), 36% multiple fractions (5 or 6x4Gy)) and were followed for six months to determine whether they developed a pathological femoral fracture. All plain radiographs available within a two month period prior to radiotherapy were obtained. Patient-specific FE models were constructed based on the geometry and bone density obtained from the baseline quantitative CT scans used for radiotherapy planning. Femoral failure loads normalized for body weight (BW) were calculated. Patients with a failure load of 7.5 x BW or lower were identified as having high fracture risk, whereas patients with a failure load higher than 7.5 x BW were classified as low fracture risk. Experienced assessors measured axial cortical involvement on conventional radiographs. Following clinical guidelines, patients with lesions larger than 30mm were identified as having a high fracture risk. FE predictions were compared to clinical assessments by means of diagnostic accuracy values (sensitivity, specificity and positive (PPV) and negative predictive values (NPV)). RESULTS: Seven femurs (14%) fractured during follow-up. Median time to fracture was 8 weeks. FE models were better at assessing fracture risk in comparison to axial cortical involvement (sensitivity 100% vs. 86%, specificity 74% vs. 42%, PPV 39% vs. 19%, and NPV 100% vs. 95%, for the FE computer model vs. axial cortical involvement, respectively). CONCLUSIONS: Patient-specific FE computer models improve fracture risk assessments of femoral bone metastases in advanced cancer patients compared to clinical assessments based on axial cortical involvement, which is currently used in clinical guidelines.

MRI-based guidelines for selective neoadjuvant treatment in rectal cancer: Does MRI adequately predict the indication for radiotherapy in daily practice in a large teaching hospital.

OBJECTIVES: According to new Dutch guidelines for rectal cancer, MRI-defined tumour stage determines whether preoperative radiotherapy is indicated. Therefore, we sought to evaluate if preoperative MRI accurately predicts the indication for neoadjuvant treatment in rectal cancer cases in daily practice according to the new Dutch guidelines. METHODS: Data for all rectal cancer patients who underwent mesorectal excision in our hospital, between January 2011 and January 2018 were collected retrospectively. We compared histopathologic outcome with tumour staging on preoperative MRI for patients who received no radiotherapy prior to resection or short-course radiotherapy directly followed by resection. RESULTS: Of 223 patients treated according to the old guidelines, 94% received neoadjuvant therapy. Of 301 patients treated according to the new guidelines, only 49% did. Under the old guidelines, MRI predicted lymph node metastases with a sensitivity of 74.2% and a specificity of 52.6%. With the new guidelines, sensitivity was 47.5% and specificity was 77.3%. The new guidelines resulted in 45% more patients not being exposed to disadvantages of radiotherapy, but 13% of all patients were undertreated. CONCLUSIONS: Concordance between clinical lymph node staging on preoperative MRI and histopathologic staging is limited, resulting in many rectal cancer patients not receiving adequate neoadjuvant therapy.

Trends in treatment and overall survival among patients with proximal esophageal cancer.

BACKGROUND: The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation (CRT) have been implemented. The trends in (non-)surgical treatment and its impact on overall survival (OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer, it is therefore essential to gain more insight through real-life studies. AIM: To establish trends in treatment and OS in patients with proximal esophageal cancer. METHODS: In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics. RESULTS: In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%, 23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval (CI): 6.4-8.1] in 1989-1994 to 9.5 mo (95%CI: 8.1-10.8) in 2010-2014 (logrank P < 0.001). In non-metastatic disease, 5-year OS rates improved from 5% (95%CI: 3%-7%) in 1989-1994 to 13% (95%CI: 9%-17%) in 2010-2014 (logrank P < 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo (95%CI: 2.5-5.1) in 1989-1994, and 5.1 mo (95%CI: 4.3-5.9) in 2010-2014 (logrank P = 0.26). CONCLUSION: OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.

Small Cell Carcinoma of the Esophagus: A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease.

BACKGROUND AND PURPOSE: Small cell carcinoma of the esophagus (SCEC) is a rare subtype of esophageal cancer for which optimal treatment is unknown. We analyzed the impact of treatment factors on outcome in patients with nonmetastasized SCEC. METHODS: Patients with a histologically confirmed SCEC without distant metastases were analyzed in a nationwide multicenter retrospective cohort. All patients received radiotherapy as part of curative treatment between January 2000 and December 2014. Details on treatment and outcome were retrieved from individual charts. Cox regression analysis was used to determine prognostic factors for survival. RESULTS: Fifty-eight patients were analyzed. Median survival was 16 months (95% confidence interval, 11-21 mo). Infield recurrences occurred in 25%, distant metastases in 45%, and brain metastases in 12%. In total, 63% of patients developed a recurrence. Most recurrences (67%) occurred within 1 year. In univariable analyses an increased number of chemotherapy cycles (>3) and lower radiotherapy doses (<45 Gy) were associated with improved survival. T-stage, N-stage, treatment period, type of chemotherapy, prophylactic cranial irradiation, and age were not associated with survival. In multivariable analyses, only the number of chemotherapy cycles was associated with better survival (hazard ratio, 0.78; P=0.006). CONCLUSIONS: SCEC recurs frequently at distant sites after definitive chemoradiotherapy and usually within 1 year after curative treatment. With a dose of 45 to 50 Gy, infield recurrence rate was low. We found a relationship between number of received chemotherapy cycles and survival with best results obtained after at least 4 cycles of chemotherapy.

Occurrence and mechanism of visual phosphenes in external photon beam radiation therapy and how to influence them.

BACKGROUND AND PURPOSE: Two plausible mechanisms to explain the appearance of visual phosphenes are: direct activation of the photochemicals in the retina and the generation of Cherenkov radiation in the vitreous humour. In this clinical trial we investigated the occurrence of visual phosphenes in external photon beam radiation therapy. MATERIAL AND METHODS: Logistic regression analysis is used to examine whether seeing light flashes and seeing steady light depended on the ambient light intensity and the dose. RESULTS: In total, 465 treatments of 25 patients were analysed. The odds of seeing light flashes multiply by 0,926 as the ambient light intensity increases by 10 lux. Similarly, the odds multiply by 1,604 as the dose to the retina increases by 10 cGy. The odds of seeing steady light multiply by 1,540 as the dose to the vitreous humour increases by 10 cGy. CONCLUSIONS: We postulate that one should reduce the dose rate, instruct patients to keep the eyes open and increase the illuminance in the treatment room to reduce the probability of experiencing visual phosphenes. We hypothesize that melanopsin is involved in the visual phosphenes and that fatigue of patients might be correlated with the observation of visual phosphenes.

Early local recurrence and one-year mortality of rectal cancer after restricting the neoadjuvant therapy regime.

INTRODUCTION: To reduce the risk of local recurrence after rectal cancer surgery, neoadjuvant radiotherapy (RT) can be applied. However, as this causes morbidity and increases mortality, new Dutch guidelines withhold RT in low-risk patients. The aim of this study is to investigate if early local recurrence and one-year mortality in rectal cancer patients has changed since this more restricting indication for neoadjuvant RT was introduced in 2014. METHODS: This retrospective study included all consecutive patients treated with a mesorectal excision for primary rectal cancer in the Amphia Hospital, the Netherlands, between January 2011 and July 2016. Data were extracted from the electronic patient records. Survival data were collected from the Municipal Personal Records Database. RESULTS: Between 2011 and July 2016, 407 resections of primary rectal cancer without synchronic metastases were performed, 225 under the old guidelines and 182 under the new guidelines. Significantly fewer patients received neoadjuvant treatment under the new guidelines (89% vs 41%, p < 0.001). Both clinical tumour stage (p = 0.001) and clinical lymph node stage (p < 0.001) were lower in the new group, but no difference in pathologic TN-stage was found. There was no difference in one-year local recurrence (2.2% in both groups, p = 0.987), nor in one-year mortality (5.3% vs 3.8%, p = 0.479). CONCLUSION: Introducing a new guideline and thereby restricting the indication for neoadjuvant RT in rectal cancer patients did not increase the early local recurrence rate or decreased one-year mortality in our hospital.

Whole-brain radiation therapy without a thermoplastic mask.

The aim of the study was to investigate the clinical feasibility of whole-brain radiation therapy without a thermoplastic mask. Positioning and intra-fractional motion monitoring were performed using optical surface scanning. The motion threshold was 3 mm/3 degrees. The group mean vector deviation was 1.1 mm. The roll was larger compared to pitch and rotation. Two patients out of 30 were not able to lie still. All other patients completed their treatment successfully without a mask. With a probability of success of 93%, we concluded that irradiation without a mask is a clinically feasible method.