Selected stage IV rectal cancer patients managed by the watch-and-wait approach after pelvic radiotherapy:a good alternative to total mesorectal excision surgery?

Aim: The aim of this study was to assess the clinical and oncological outcome of a selected group of stage IV rectal cancer patients managed by the watch-and-wait approach following a (near-)complete response of the primary rectal tumour after radiotherapy. Method: Patients registered in the Dutch watch-and-wait registry since 2004 were selected when diagnosed with synchronous stage IV rectal cancer. Data on patient characteristics, treatment details, follow-up and survival were collected. The 2-year local regrowth rate, organ-preservation rate, colostomy-free rate, metastatic progression-free rate and 2- and 5-year overall survival were analysed. Results: After a median follow-up period of 35 months, local regrowth was observed in 17 patients (40.5%). Nine patients underwent subsequent total mesorectal excision, resulting in a permanent colostomy in four patients. The 2-year local regrowth rate was 39.9%, the 2-year organ-preservation rate was 77.1%, the 2-year colostomy-free rate was 88.1%, and the 2-year metastatic progression-free rate was 46.7%. The 2- and 5-year overall survival rates were 92.0% and 67.5%. Conclusion: The watch-and-wait approach can be considered as an alternative to total mesorectal excision in a selected group of stage IV rectal cancer patients with a (near-)complete response following pelvic radiotherapy. Despite a relatively high regrowth rate, total mesorectal excision and a permanent colostomy can be avoided in the majority of these patients.</p

Selected stage IV rectal cancer patients managed by the watch-and-wait approach after pelvic radiotherapy:a good alternative to total mesorectal excision surgery?

Aim: The aim of this study was to assess the clinical and oncological outcome of a selected group of stage IV rectal cancer patients managed by the watch-and-wait approach following a (near-)complete response of the primary rectal tumour after radiotherapy. Method: Patients registered in the Dutch watch-and-wait registry since 2004 were selected when diagnosed with synchronous stage IV rectal cancer. Data on patient characteristics, treatment details, follow-up and survival were collected. The 2-year local regrowth rate, organ-preservation rate, colostomy-free rate, metastatic progression-free rate and 2- and 5-year overall survival were analysed. Results: After a median follow-up period of 35 months, local regrowth was observed in 17 patients (40.5%). Nine patients underwent subsequent total mesorectal excision, resulting in a permanent colostomy in four patients. The 2-year local regrowth rate was 39.9%, the 2-year organ-preservation rate was 77.1%, the 2-year colostomy-free rate was 88.1%, and the 2-year metastatic progression-free rate was 46.7%. The 2- and 5-year overall survival rates were 92.0% and 67.5%. Conclusion: The watch-and-wait approach can be considered as an alternative to total mesorectal excision in a selected group of stage IV rectal cancer patients with a (near-)complete response following pelvic radiotherapy. Despite a relatively high regrowth rate, total mesorectal excision and a permanent colostomy can be avoided in the majority of these patients.</p

Delay in Diagnostic Workup and Treatment of Esophageal Cancer

Introduction: Esophageal cancer should preferably be detected and treated at an early stage, but this may be prohibited by late onset of symptoms and delays in referral, diagnostic workup, and treatment. The aim of this study was to investigate the impact of these delays on outcome in patients with esophageal cancer. Methods: For 491 patients undergoing esophagectomy for cancer between 1991 and 2007, patients' short- and long-term outcome were analyzed according to different time intervals between onset of symptoms, diagnosis, and surgical treatment. Results: Length of prehospital delay (from onset of symptoms until endoscopic diagnosis) did not affect patient's short- or long-term outcome. A shorter hospital delay between establishing the diagnosis of esophageal cancer on endoscopy and surgery was associated with lower overall morbidity and in-hospital mortality. Patients of ASA classes I and II experienced a shorter hospital delay than patients of ASA classes III and IV. Length of hospital delay between endoscopic diagnosis and surgery did not affect pathological tumor-node-metastasis stage or R0-resection rate. Longer hospital delay did not result in worse survival: Overall survival after esophagectomy for cancer was not significantly different between patients with hospital delay 8 weeks (24. 7%, 21. 7%, and 32. 3%, respectively; p = 0. 12). Conclusion: A longer hospital delay (between endoscopic diagnosis and surgery) resulted in worse patient's short-term outcome (higher overall morbidity and mortality rates) but not in a worse long-term outcome (overall survival). This may be explained by a more time-consuming diagnostic workup in patients with a poorer physical status and not by tumor progression

Role of Local Excision for Suspected Regrowth in a Watch and Wait Strategy for Rectal Cancer

Simple Summary Rectal cancer patients with a clinical complete response to neoadjuvant treatment are eligible for Watch and Wait as an alternative to total mesorectal excision. However, in patients with local regrowth, major surgery is still the standard of care. The present study evaluates the role of local excision for suspected local regrowth in a large Watch and Wait cohort, in terms of long-term outcomes. This study shows excellent overall survival and a good organ preservation rate. Patients who developed locoregional recurrence after initial local excision for regrowth were all successfully treated with salvage surgery. This study shows that local excision can provide maintenance of organ preservation without an obvious compromise in surgical or oncological safety. Local excision for suspected regrowth in patients following Watch and Wait can be a safe alternative for total mesorectal excision in selected patients with a strong wish to preserve their rectum. Rectal cancer patients with a clinical complete response to neoadjuvant (chemo)radiation are eligible for Watch and Wait (W&W). For local regrowth, total mesorectal excision (TME) is considered the standard of care. This study evaluated local excision (LE) for suspected local regrowth. From 591 patients prospectively entered into a national W&W registry, 77 patients with LE for regrowth were included. Outcomes analyzed included histopathologic findings, locoregional recurrence, long-term organ preservation, and colostomy-free and overall survival. In total, 27/77 patients underwent early LE (= 6 months). Median follow-up was 53 (39-69) months. In 28/77 patients the LE specimen was histopathologically classified as ypT0 (including 9 adenomas); 11/77 were ypT1, and 38/77 were ypT2-3. After LE, 13/77 patients with ypT2-3 and/or irradical resection underwent completion TME. Subsequently, 14/64 patients without completion TME developed locoregional recurrence, and were successfully treated with salvage TME. Another 8/77 patients developed distant metastases. At 5 years, overall organ preservation was 63%, colostomy-free survival was 68%, and overall survival was 96%. There were no differences in outcomes between early or late LE. In W&W for rectal cancer, LE can be considered as an alternative to TME for suspected regrowth in selected patients who wish to preserve their rectum or avoid colostomy in distal rectal cancer

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer – implications for the development of new imaging modalities for response assessment

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment.</p

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer – implications for the development of new imaging modalities for response assessment

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial

INTRODUCTION: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT. METHODS AND ANALYSIS: The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int)

Optimal surgical approach to esophagectomy for cancer

Surgery is the primary curative therapy for patients with esophageal cancer. It is now widely recognized that a surgical procedure such as esophagectomy has lower mortality and morbidity rates when performed in high-volume centers. Nevertheless, esophagectomy is still associated with a substantial operative risk. For continuous improvement of esophagectomy outcome, an optimal treatment strategy should not only be based on proper patient selection by means of accurate staging and preoperative risk assessment. Optimization of the surgical approach for patients with esophageal cancer has also been the focus of many studies over the last years.</p