The treatment of recurrent endometrial cancer is a challenge. Because of earlier treatments and the site of locoregional recurrence, in the vaginal vault or pelvis, morbidity can be high. A total of about 4 to 20% of the patients with endometrial cancer develop a locoregional recurrence, mostly among patients with locally advanced disease. The treatment options are dependent on previous treatments and the site of recurrence. Local and locoregional recurrences can be treated curatively with surgery or (chemo)radiotherapy with acceptable toxicity and control rates. Distant recurrences can be treated with palliative systemic therapy, i.e., first-line chemotherapy or hormonal therapy. Based on the tumor characteristics and molecular profile, there can be a role for immunotherapy. The evidence on targeted therapy is limited, with no approved treatment in the current guidelines. In selected cases, there might be an indication for local treatment in oligometastatic disease. Because of the novel techniques in radiotherapy, disease control can often be achieved at limited toxicity. Further studies are warranted to analyze the survival outcome and toxicity of newer treatment strategies. Patient selection is very important in deciding which treatment is of most benefit, and better prediction models based on the patient- and tumor characteristics are necessary.

Patients diagnosed with locally advanced esophageal cancer are often treated with neoadjuvant chemoradiotherapy followed by surgery. This study explored whether detection of circulating tumor DNA (ctDNA) in plasma can be used to predict residual disease during treatment. Diagnostic tissue biopsies from patients with esophageal cancer receiving neoadjuvant chemoradiotherapy and surgery were analyzed for tumor-specific mutations. These tumor-informed mutations were used to measure the presence of ctDNA in serially collected plasma samples using hybrid capture-based sequencing. Plasma samples were obtained before chemoradiotherapy, and prior to surgery. The association between ctDNA detection and progression-free and overall survival was measured. Before chemoradiotherapy, ctDNA was detected in 56% (44/78) of patients and detection was associated with tumor stage and volume (p = 0.05, Fisher exact and p = 0.02, Mann-Whitney, respectively). After chemoradiotherapy, ctDNA was detected in 10% (8/78) of patients. This preoperative detection of ctDNA was independently associated with recurrent disease (hazard ratio 2.8, 95% confidence interval 1.1–6.8, p = 0.03, multivariable Cox-regression) and worse overall survival (hazard ratio 2.9, 95% confidence interval 1.2–7.1, p = 0.02, multivariable Cox-regression).Ultradeep sequencing-based detection of ctDNA in preoperative plasma of patients with locally advanced esophageal cancer may help to assess which patients have a high risk of recurrence after neoadjuvant chemoradiotherapy and surgery.

In rectal cancer patients, radiotherapy in prone position using a belly board can reduce the dose to organs at risk. For this patient group we investigated inter-fraction shape variation of the mesorectal part of the clinical target volume (CTV) and determined planning target volume (PTV) margins. Patients with rectal cancer receiving neoadjuvant (chemo)radiotherapy were eligible. For each patient a planning computed tomography (pCT) and five cone-beam CT (CBCT) scans were acquired in prone position using a belly board. The mesorectal CTV was delineated on all scans. Mesorectal shape variation was quantified relative to the pCT. PTV margins were derived locally and averaged for separate subregions of the mesorectal CTV. For each patient a total PTV was constructed using our clinical margins for mesorectal and lymph node CTVs. An artificial dose distribution conforming to this PTV was used to calculate the coverage for the mesorectal CTV using the CBCT delineations. In 19 rectal cancer patients the derived PTV margins were smallest in the upper-lateral region (6 mm) and largest in the upper-anterior region (16 mm). PTV margins for the upper-anterior region were larger for female patients (19 mm) compared to male patients (14 mm). Clinical margins for the total PTV were sufficient for a coverage of at least 97% of the mesorectal CTV for all patients. Mesorectal shape variation is heterogeneous and largest in the upper-anterior region, in rectal cancer patients irradiated in prone position and using a belly board.

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).

Prevention of treatment-related complications remains a major challenge in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) ± surgery. A single measure, reflecting the total complication burden, may provide a clear overall picture of patient burden and enables a direct comparison of alternative treatment strategies. We developed a Complication Sum Score (CSS) to quantify symptomatic complications. A Delphi consensus procedure was used to develop the CCS using the expertise of health professionals to assess the impact of a spectrum of complications. The impact of each complication was scored on a 0–100 scale. Consensus for these scores was defined as an interquartile range ≤ 20. The association between the CSS and hospital/ICU stay, overall survival (OS) at 1 year and quality of life (QoL) was assessed in a multicenter dataset of patients with EC, using multivariable (logistic) regression analysis, correcting for possible confounders. Forty-five experts completed the two-round Delphi procedure. Consensus was reached for all (36) complications. In 1225 patients, that underwent nCRT and esophagectomy, a higher CSS was significantly associated with a longer hospital (coefficient = 0.43[0.38–0.48], p < 0.01) and ICU stay (coefficient = 0.23[0.19–0.26], p < 0.01), and a worse OS (odds ratio = 1.005[1.004–1.006], p < 0.01). Among the patients that completed a QoL questionnaire after surgery (n = 98) an increased CSS was associated with worse QoL (coefficient = -0.24[-0.01–0.49], p = 0.06). The CSS offers a comprehensive tool to quantify treatment-related complications in a single score in EC patients that receive nCRT followed by surgical resection.