Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. ...However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians.
Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes.
In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88–26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9–6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1–32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5–19.4, p < 0.001).
When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence.
A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy ...(TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT.
Comparison between patients with pCR in the RAPIDO trial in the experimental EXP (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment STD (CRT, surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR.
Among patients with a resection within six months after preoperative treatment, 120/423 (28%) EXP and 57/398 (14%) STD achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32–3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51–3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83–3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (Pinteraction=0.042). pCR rates did not increase with prolonged treatment time.
The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size.
•TNT results in a doubled pCR rate compared to CRT.•A pCR following TNT or CRT leads to similar, favourable oncological outcomes.•Α tumour size < 40 mm, CEA < 5, cT2-stage and TNT are associated with achieving pCR.•pCR rates did not increase with prolonged treatment time within each treatment.
Patients undergoing complex gastrointestinal surgery are at high risk of major postoperative complications (e.g., anastomotic leakage, sepsis), classified as Clavien-Dindo (CD) ≥ IIIa. Identification ...of preoperative risk factors can lead to the identification of high-risk patients. These risk factors can also be used to design personalized perioperative care. This systematic review focuses on the identification of these factors. The Medline and Embase databases were searched for prospective, retrospective cohort studies and randomized controlled trials investigating the effect of risk factors on the occurrence of major postoperative complications and/or mortality after complex gastrointestinal cancer surgery. Risk of bias was assessed using the Quality in Prognostic Studies tool. The level of evidence was graded based on the number of studies reporting a significant association between risk factors and major complications. A total of 207 eligible studies were retrieved, identifying 33 risk factors for major postoperative complications and 13 preoperative laboratory results associated with postoperative complications. The present systematic review provides a comprehensive overview of preoperative risk factors associated with major postoperative complications. A wide range of risk factors are amenable to actions in perioperative care and prehabilitation programs, which may lead to improved outcomes for high-risk patients. Additionally, the knowledge of this study is important for benchmarking surgical outcomes.
Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from ...infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn's disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas.
Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical ...complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait.
The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD).
In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998).
There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment.
Summary Background In many patients with rectal cancer, defunctioning stomas are created to limit the consequences of anastomotic leakage. Although intended to be temporary, a substantial proportion ...of these stomas might never be reversed for various reasons. We aimed to describe stoma policy by use of data from the total mesorectal excision (TME) trial in patients with rectal cancer and to identify factors that limit stoma reversal. Methods 924 Dutch patients with rectal cancer who underwent a low anterior resection were selected from the TME trial, a prospective, randomised multicentre trial studying the effects of short-term preoperative radiotherapy in 1861 patients who underwent TME. Creation of stomas and time to stoma reversal were analysed retrospectively by use of multivariate analysis. Findings In 523 of 924 (57%) patients, a primary stoma (defined as a stoma created at the time of TME) was constructed after a low anterior resection. Geographical differences in the number of primary stomas constructed were reported throughout the Netherlands. 19% of stomas that were created were never reversed. Postoperative complications and secondary constructed stomas (defined as a stoma created during a second or subsequent procedure after TME) were associated with a high likelihood of a permanent stoma. However, perioperative complications were not a limiting factor for stoma closure. Interpretation Postoperative complications are an important limiting factor for stoma reversal because, after occurrence of these complications, patients and surgeons might be reluctant to reverse the stoma, so a substantial proportion of these stomas are never closed. Future guidelines for stoma creation and closure should consider these factors.
Background
Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging ...dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC.
Methods
Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose.
Results
Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (
p
= 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients.
Conclusions
The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.
As the survival of patients with rectal cancer has improved in recent decades, more and more patients have to live with the consequences of rectal cancer surgery. An influential factor in long-term ...Health-related Quality of Life (HRQoL) is the presence of a stoma. This study aimed to better understand the long-term consequences of a stoma and poor functional outcomes.
Patients who underwent curative surgery for a primary tumor located in the rectosigmoid and rectum between 2013 and 2020 were identified from the nationwide Prospective Dutch Colorectal Cancer (PLCRC) cohort study. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, and the LARS-score at 12 months, 24 months and 36 months after surgery.
A total of 1,170 patients were included of whom 751 (64.2%) had no stoma, 122 (10.4%) had a stoma at primary surgery, 45 (3.8%) had a stoma at secondary surgery and 252 (21.5%) patients that underwent abdominoperineal resection (APR). Of all patients without a stoma, 41.4% reported major low-anterior resection syndrome (LARS). Patients without a stoma reported significantly better HRQoL. Moreover, patients without a stoma significantly reported an overall better HRQoL.
The presence of a stoma and poor functional outcomes were both associated with reduced HRQoL. Patients with poor functional outcomes, defined as major LARS, reported a similar level of HRQoL compared to patients with a stoma. In addition, the HRQoL after rectal cancer surgery does not change significantly after the first year after surgery.
BackgroundExpression of CD103 and CD39 has been found to pinpoint tumor-reactive CD8+ T cells in a variety of solid cancers. We aimed to investigate whether these markers specifically identify ...neoantigen-specific T cells in colorectal cancers (CRCs) with low mutation burden.Experimental designWhole-exome and RNA sequencing of 11 mismatch repair-proficient (MMR-proficient) CRCs and corresponding healthy tissues were performed to determine the presence of putative neoantigens. In parallel, tumor-infiltrating lymphocytes (TILs) were cultured from the tumor fragments and, in parallel, CD8+ T cells were flow-sorted from their respective tumor digests based on single or combined expression of CD103 and CD39. Each subset was expanded and subsequently interrogated for neoantigen-directed reactivity with synthetic peptides. Neoantigen-directed reactivity was determined by flow cytometric analyses of T cell activation markers and ELISA-based detection of IFN-γ and granzyme B release. Additionally, imaging mass cytometry was applied to investigate the localization of CD103+CD39+ cytotoxic T cells in tumors.ResultsNeoantigen-directed reactivity was only encountered in bulk TIL populations and CD103+CD39+ (double positive, DP) CD8+ T cell subsets but never in double-negative or single-positive subsets. Neoantigen-reactivity detected in bulk TIL but not in DP CD8+ T cells could be attributed to CD4+ T cells. CD8+ T cells that were located in direct contact with cancer cells in tumor tissues were enriched for CD103 and CD39 expression.ConclusionCoexpression of CD103 and CD39 is characteristic of neoantigen-specific CD8+ T cells in MMR-proficient CRCs with low mutation burden. The exploitation of these subsets in the context of adoptive T cell transfer or engineered T cell receptor therapies is a promising avenue to extend the benefits of immunotherapy to an increasing number of CRC patients.
To optimize therapeutic decision-making in early invasive colorectal cancer (T1 CRC) patients, it is important to elicit the patient’s perspective next to considering medical outcome. Because ...empirical data on patient-reported impact of different treatment options are lacking, we evaluated patients’ quality of life, perceived time to recovery, and fear of cancer recurrence after endoscopic or surgical treatment for T1 CRC.
In this cross-sectional study, we selected patients with histologically confirmed T1 CRC who participated in the Dutch Bowel Cancer Screening Programme and received endoscopic or surgical treatment between January 2014 and July 2017. Quality of life was measured using the European Organization for Research and Treatment 30-item Core Quality of Life Questionnaire and the 5-level EuroQoL 5-dimension questionnaire. We used the Cancer Worry Scale (CWS) to evaluate patients’ fear of cancer recurrence. A question on perceived time to recovery after treatment was also included in the set of questionnaires sent to patients.
Of all 119 eligible patients, 92.4% responded to the questionnaire (endoscopy group, 55/62; surgery group, 55/57). Compared with the surgery group, perceived time to recovery was on average 3 months shorter in endoscopically treated patients after adjustment for confounders (19.9 days vs 111.3 days; P = .001). The 2 treatment groups were comparable with regard to global quality of life, functioning domains, and symptom severity scores. Moreover, patients in the endoscopy group did not report more fear of cancer recurrence than those in the surgery group (CWS score, 0-40; endoscopy 7.6 vs surgery 9.7; P = .140).
From the patient’s perspective, endoscopic treatment provides a quicker recovery than surgery, without provoking more fear of cancer recurrence or any deterioration in quality of life. These results contribute to the shared therapeutic decision-making process of clinicians and T1 CRC patients.
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