Veronique E. Mul

Does screening for distress efficiently uncover meetable unmet needs in cancer patients

Objectives: We evaluated screening for distress in terms of its ability to uncover unmet need for psychosocial services in cancer patients. Correlates of distress, need for services and met and unmet need for services were investigated.

A systematic review on the role of FDG-PET/CT in tumour delineation and radiotherapy planning in patients with esophageal cancer

PURPOSE FDG-PET/CT has proven to be useful in the staging process of esophageal tumours. This review analysed the role of FDG-PET/CT in tumour delineation and radiotherapy planning in comparison with CT alone among patients with esophageal cancer. Thereby we focused on the detection of the primary tumour and lymph nodes by FDG-PET/CT, changes in target volume (TV) delineation based on FDG-PET/CT and its validity, changes in inter- and intra-observer variability in TV delineation, consequences for radiotherapy treatment planning with regard to either target volumes or organs at risk and finally on the validation of FDG-PET/CT-based TVs in terms of treatment outcome. METHODS A literature search was performed in MEDLINE and Cochrane library databases for studies concerning the current value of FDG-PET/CT in tumour detection and delineation and radiotherapy-planning procedures among patients with esophageal cancer. Both prospective and retrospective studies were included. RESULTS Fifty publications met the eligibility criteria, of which 19 were review papers and one was a case report. The remaining 30 publications reported on the results of original studies. FDG-PET was able to identify most primary tumours, with a sensitivity and specificity for the detection of metastatic lymph nodes of 30-93% and 79-100%. The use of FDG-PET/CT resulted in changes of target volumes, and consequently in changes in treatment planning. However, evidence supporting the validity of the use of FDG-PET/CT in the tumour delineation process is very limited. Only three studies reported a significant positive correlation between FDG-PET-based tumour lengths and pathological findings. There were two studies that tested the influence of FDG-PET/CT to the inter- and intra-observer variability. One of them found a significant decrease in inter- and intra-observer variability, while the others did not. Furthermore, there are no studies demonstrating the use of PET/CT in terms of improved locoregional control or survival. CONCLUSION Since the literature is very limited standard implementation of FDG-PET/CT into the tumour delineation process for radiation treatment seems unjustified and needs further clinical validation first.

External beam radiotherapy combined with intraluminal brachytherapy in esophageal carcinoma

PURPOSE To assess the effectiveness of definitive radiation therapy in patients with potentially curable esophageal cancer and to evaluate the side-effects of this treatment. METHODS AND MATERIALS Sixty-two patients with esophageal cancer, who were treated with definitive, curatively intended radiotherapy consisting of external radiotherapy (60 Gy in 30 fractions), preceded and followed by LDR or HDR intraluminal brachy (12 Gy in 2 fractions) were retrospectively analyzed. RESULTS Recurrences were reported in 38 patients (61%), of which 25 (64%) failed locally first. The overall survival rates at 1, 2 and 5 years were 57%, 34% and 11%, respectively. The median overall survival was 15 months. No prognostic factors could be identified. Most frequently reported treatment related toxicities were esophagitis, ulcerations, (11%) and strictures (16%). In 10 patients (16%) severe toxicities, were reported including grade III ulceration (2 cases), stricture (1 case), radiation pneumonitis (1 case), perforation (1 case), esophageal-pleural-tracheal fistula (1 case), and acute esophageal bleeding (4 cases). A history of gastrectomy was significantly associated with the development of severe toxicity. CONCLUSION Curatively intended radiotherapy alone can be offered to esophageal cancer patients, even when surgery and/or chemotherapy are not feasible. However, we observed severe toxicity in a substantial part of the patients. Given the relatively high rate of severe complications and the uncertainties regarding dose escalation, the addition of brachytherapy, with consequently high surface doses, should be limited to well-selected patients.

Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

PURPOSE/OBJECTIVE(S) The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. METHODS AND MATERIALS The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. RESULTS After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). CONCLUSIONS Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.

Increased risk of thromboembolism in esophageal cancer patients treated with neoadjuvant chemoradiotherapy

BACKGROUND Neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients may increase the formation of thromboembolic events (TEEs). We analyzed the incidence and impact of TEEs in EC patients treated with platinum-based CRT. METHODS A total of 336 patients with EC underwent an esophagectomy, of which 110 patients received neoadjuvant CRT (41.4 Gy with concurrent Carboplatin/Paclitaxel). Patients were matched based on pre- and perioperative characteristics. RESULTS Preoperatively, 9 (8.2%) patients with neoadjuvant CRT (P = .004) were diagnosed with TEEs. Despite delay until surgery (P = .021), the postoperative course did not differ. In multivariate analysis, a history of deep vein thrombosis (P = .005) and neoadjuvant CRT (P = .004) were identified as risk factors. Postoperatively, there were no differences in TEEs (P = .560) observed. In multivariate analysis, a history of pulmonary embolism (P = .012) was identified as a risk factor for postoperative TEEs. CONCLUSIONS Preoperatively, EC patients treated with neoadjuvant CRT have an increased risk to develop a TEE, especially those with a previous history of TEE. After surgery no increased incidence was observed. We recommend secondary prophylaxis during neoadjuvant treatment in this high-risk group.

CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.

BACKGROUND AND PURPOSE Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype. MATERIAL AND METHODS 101 EC patients treated with nCRT and surgery were included. Sufficient pre-treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group. RESULTS Low CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed. CONCLUSIONS Low expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT.

Clinical validation of FDG-PET/CT in the radiation treatment planning for patients with oesophageal cancer.

BACKGROUND The aim of this prospective study was to determine the proportion of locoregional recurrences (LRRs) that could have been prevented if radiotherapy treatment planning for oesophageal cancer was based on PET/CT instead of CT. MATERIALS AND METHODS Ninety oesophageal cancer patients, eligible for high dose (neo-adjuvant) (chemo)radiotherapy, were included. All patients underwent a planning FDG-PET/CT-scan. Radiotherapy target volumes (TVs) were delineated on CT and patients were treated according to the CT-based treatment plans. The PET images remained blinded. After treatment, TVs were adjusted based on PET/CT, when appropriate. Follow up included CT-thorax/abdomen every 6months. If LRR was suspected, a PET/CT was conducted and the site of recurrence was compared to the original TVs. If the LRR was located outside the CT-based clinical TV (CTV) and inside the PET/CT-based CTV, we considered this LRR possibly preventable. RESULTS Based on PET/CT, the gross tumour volume (GTV) was larger in 23% and smaller in 27% of the cases. In 32 patients (36%), >5% of the PET/CT-based GTV would be missed if the treatment planning was based on CT. The median follow up was 29months. LRRs were seen in 10 patients (11%). There were 3 in-field recurrences, 4 regional recurrences outside both CT-based and PET/CT-based CTV and 3 recurrences at the anastomosis without changes in TV by PET/CT; none of these recurrences were considered preventable by PET/CT. CONCLUSION No LRR was found after CT-based radiotherapy that could have been prevented by PET/CT. The value of PET/CT for radiotherapy seems limited.

Is implementing screening for distress an efficient means to recruit patients to a psychological intervention trial

Psychological interventions show greater efficacy when evaluated with distressed patients. We report on the feasibility of implementing screening for recruiting distressed cancer patients to a randomized controlled trial of problem‐solving therapy (PST), characteristics associated with enrolment, and time investment and challenges of implementing screening.

Predicting response to neoadjuvant chemoradiotherapy in esophageal cancer with textural features derived from pre-treatment 18F-FDG PET/CT imaging

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUVmax in 18F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18F-FDG PET/CT–derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18F-FDG PET and CT. The current most accurate prediction model with SUVmax as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model’s performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2–5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18F-FDG PET–derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUVmax model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUVmax). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery.

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer

Purpose To assess the value of baseline and restaging fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer.