Treatments for colorectal cancer (CRC) of all stages have evolved considerably over the past two decades, resulting in improved long-term outcomes. After curative treatment, however, 30% of patients ...with stage I-III and up to 65% of patients with stage IV CRC develop recurrent disease. Thus, patients are routinely offered surveillance in order to detect disease recurrence at an early, asymptomatic stage, with the intention of improving survival. Nevertheless, controversy continues to surround the optimal surveillance protocols. For patients with stage I-III CRC, more-intensive surveillance improves overall survival compared with less-intensive or no surveillance, probably owing to improved outcomes after cancer recurrence, as well as proactive treatment of other conditions detected opportunistically. The benefit of surveillance after curative treatment of stage IV CRC is more controversial, but might be justified because repeat resection can improve overall survival and 20% of these patients are eligible for such treatment with curative intent. No trials have assessed the optimal follow-up approach after curative resection of metastatic CRC, and similarly to surveillance of patients with stage I-III disease, most programmes are more intensive during the first 3 years than at later time points. Herein, we provide a comprehensive overview of surveillance strategies for patients with CRC, and discuss the future development of patient-centred programmes.
PD-1/PD-L1-checkpoint blockade therapy is generally thought to relieve tumor cell-mediated suppression in the tumor microenvironment but PD-L1 is also expressed on non-tumor macrophages and ...conventional dendritic cells (cDCs). Here we show in mouse tumor models that tumor-draining lymph nodes (TDLNs) are enriched for tumor-specific PD-1+ T cells which closely associate with PD-L1+ cDCs. TDLN-targeted PD-L1-blockade induces enhanced anti-tumor T cell immunity by seeding the tumor site with progenitor-exhausted T cells, resulting in improved tumor control. Moreover, we show that abundant PD-1/PD-L1-interactions in TDLNs of nonmetastatic melanoma patients, but not those in corresponding tumors, associate with early distant disease recurrence. These findings point at a critical role for PD-L1 expression in TDLNs in governing systemic anti-tumor immunity, identifying high-risk patient groups amendable to adjuvant PD-1/PD-L1-blockade therapy.
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•Tumor-draining lymph nodes (TDLNs) are enriched for tumor-specific PD-1+ T cells•Blocking PD-L1 in TDLNs generates progenitor-exhausted T cells that seed the tumor•PD-L1 blockade on cDCs, not macrophages in TDLNs induces effective tumor immunity•PD-1/PD-L1 interactions in TDLN but not tumor correlate with prognosis in melanoma
Dammeijer et al. show that PD-1/PD-L1 interactions occur frequently in tumor-draining lymph nodes (TDLNs) and that specific targeting of PD-L1 in the TDLN induces an effective anti-tumor immune response in multiple mouse models. In addition, PD-1/PD-L1 interactions in TDLNs, but not in tumor, correlate with prognosis in melanoma patients.
OBJECTIVE:The aim of this study was to compare adhesion formation after laparoscopic and open colorectal cancer resection.
SUMMARY OF BACKGROUND DATA:After colorectal surgery, most patients develop ...adhesions, with a high burden of complications. Laparoscopy seems to reduce adhesion formation, but evidence is poor. Trials comparing open- and laparoscopic colorectal surgery have never assessed adhesion formation.
METHODS:Data on adhesions were gathered during resection of colorectal liver metastases. Incidence of adhesions adjacent to the original incision was compared between patients with previous laparoscopic- and open colorectal resection. Secondary outcomes were incidence of any adhesions, extent and severity of adhesions, and morbidity related to adhesions or adhesiolysis.
RESULTS:Between March 2013 and December 2015, 151 patients were included. Ninety patients (59.6%) underwent open colorectal resection and 61 patients (40.4%) received laparoscopic colorectal resection. Adhesions to the incision were present in 78.9% after open and 37.7% after laparoscopic resection (P < 0.001). The incidence of abdominal wall adhesions and of any adhesion was significantly higher after open resection; the incidence of visceral adhesions did not significantly differ. The extent of abdominal wall and visceral adhesions and the median highest Zühlke score at the incision were significantly higher after open resection. There were no differences in incidence of small bowel obstruction during the interval between the colorectal and liver operations, the incidence of serious adverse events, and length of stay after liver surgery.
CONCLUSION:Laparoscopic colorectal cancer resection is associated with a lower incidence, extent, and severity of adhesions to parietal surfaces. Laparoscopy does not reduce the incidence of visceral adhesions.
Background
Aggressive fibromatosis (AF) is a locally infiltrating soft-tissue tumor. In a population-based study in the Netherlands, we evaluated time trends for the incidence and treatment of AF.
...Methods
In PALGA: Dutch Pathology Registry, all patients diagnosed between 1993 and 2013 as having extra-abdominal or abdominal wall aggressive fibromatosis were identified and available pathology data of the patients were evaluated. Epidemiological and treatment-related factors were analyzed with
χ
2
and regression analysis.
Results
During the study period, 1134 patients were identified. The incidence increased from 2.10 to 5.36 per million people per year. Median age at the time of diagnosis increased annually by B 0.285
(P
= 0.001). Female gender prevailed and increased over time annual odds ratio (OR) 1.022;
P
= 0.058. All anatomic localizations, but in particular truncal tumors, became more frequent. During the study period diagnostic histological biopsies were performed more often (annual OR 1.096;
P
< 0.001). The proportion of patients who underwent surgical treatment decreased (annual OR 0.928;
P
< 0.001). When resection was preceded by biopsy, 49.8 % of the patients had R0-resection versus 30.7 % in patients without biopsy (
P
< 0.001).
Conclusions
In this population-based study, an increasing incidence of extra-abdominal and abdominal-wall aggressive fibromatosis was observed. The workup of patients improved and a trend towards a nonsurgical treatment policy was observed.
Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free ...survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg
and nivolumab 3 mg kg
. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3-4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab.
Abstract
Background
Previous trials found that more intensive postoperative surveillance schedules did not improve survival. Oncological follow-up also provides an opportunity to address ...psychological issues (for example anxiety, depression, and fear of recurrence). This systematic review assessed the impact of a less intensive surveillance strategy on health-related quality of life (HRQoL), emotional well-being, and patient satisfaction.
Methods
A systematic search was conducted in PubMed/MEDLINE, Embase, Web of Science, Cochrane database, PsycINFO, and Google Scholar to identify studies comparing different follow-up strategies after oncological surgery and their effect on HRQoL and patient satisfaction, published before 4 May 2022. A meta-analysis was conducted on the most relevant European Organisation for Research and Treatment of Cancer QLQ-C30 and Hospital Anxiety and Depression Scale subscales.
Results
Thirty-five studies were identified, focusing on melanoma (4), colorectal (10), breast (7), prostate (4), upper gastrointestinal (4), gynaecological (3), lung (2), and head and neck (1) cancers. Twenty-two studies were considered to have a low risk of bias, of which 14 showed no significant difference in HRQoL between follow-up approaches. Five studies with a low risk of bias showed improved HRQoL or emotional well-being with a less intensive follow-up approach and three with an intensive approach. Meta-analysis of HRQoL outcomes revealed no negative effects for patients receiving less intensive follow-up.
Conclusion
Low-intensity follow-up does not diminish HRQoL, emotional well-being, or patient satisfaction.
The results of this review suggest that a lower-intensity follow-up approach is non-inferior and, in some instances, even results in slightly better health-related quality of life (HRQoL) and lower anxiety rates. Additionally, previous studies and a recently published systematic review failed to show any (cancer-specific) survival benefit of intensive postoperative surveillance compared with a less intensive approach. Overall, these findings enable a reduction in follow-up intensity for patients with cancer without impact on the main purposes of follow-up: cancer-specific survival and HRQoL. It can be concluded that a patient-tailored follow-up approach is feasible.
Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the ...distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.
Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined.
Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006).
The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.
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