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Supplementary Table S1 from Circumferential Margin Involvement Is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

Purpose: After preoperative (radio)chemotherapy, histologic determinants for prognostification have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival.Experimental Design: A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (Results: Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively).Conclusions: Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapy-induced regression.

BACKGROUND AND PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) is used in locally recurrent rectal cancer (LRRC) to increase chances of a radical surgical resection. Delineation in LRRC is hampered by complex disease presentation and limited clinical exposure. Within the PelvEx II trial, evaluating the benefit of chemotherapy preceding nCRT for LRRC, a delineation guideline was developed by an expert LRRC team.MATERIALS AND METHODS: Eight radiation oncologists, from Dutch and Swedish expert centres, participated in two meetings, delineating GTV and CTV in six cases. Regions at-risk for re-recurrence or irradical resection were identified by eleven expert surgeons and one expert radiologist. Target volumes were evaluated multidisciplinary. Inter-observer variation was analysed.RESULTS: Inter-observer variation in delineation of LRRC appeared large. Multidisciplinary evaluation per case is beneficial in determining target volumes. The following consensus regarding target volumes was reached. GTV should encompass all tumour, including extension into OAR if applicable. If the tumour is in fibrosis, GTV should encompass the entire fibrotic area. Only if tumour can clearly be distinguished from fibrosis, GTV may be reduced, as long as the entire fibrotic area is covered by the CTV. CTV is GTV with a 1 cm margin and should encompass all at-risk regions for irradical resection or re-recurrence. CTV should not be adjusted towards other organs. Multifocal recurrences should be encompassed in one CTV. Elective nodal delineation is only advised in radiotherapy-naïve patients.CONCLUSION: This study provides a first consensus-based delineation guideline for LRRC. Analyses of re-recurrences is needed to understand disease behaviour and to optimize delineation guidelines accordingly.

Contains fulltext : 291092.pdf (Publisher’s version ) (Open Access) The prognostic value of microsatellite instability (MSI), as well as other histological characteristics such as lymphovascular invasion (LI), perineural invasion (PNI) and extramural vascular invasion (EMVI), is unclear in colorectal mucinous carcinoma (MC). This study aims to determine the relevance of these factors in MC patients and analyses the role of MSI in stage III MC patients treated with adjuvant chemotherapy. A cohort of 650 patients diagnosed with stages I-IV colonic MC from 2000 to 2010 was selected from PALGA, the nationwide Dutch pathology databank. Histopathology was revised and mismatch repair (MMR) status determined. Univariate and multivariate survival analyses were performed. Deficient MMR (dMMR) was found in 33% of MCs and correlated with female gender and right-sidedness, but also with lower tumour stage (stages I/II: 73.2 versus 47%; P

Background This study aimed to investigate the agreement between magnetic resonance tumour regression grade (mrTRG) and pathological regression grade (pTRG) in patients with locally recurrent rectal cancer (LRRC). Also, the reproducibility of mrTRG was investigated. Methods All patients with LRRC who underwent a resection between 2010 and 2018 after treatment with induction chemotherapy and neoadjuvant chemo(re)irradiation in whom a restaging MRI was available were retrospectively selected. All MRI scans were reassessed by two independent radiologists using the mrTRG, and the pTRG was reassessed by an independent pathologist. The interobserver agreement between the radiologists as well as between the radiologists and the pathologist was assessed with the weighted kappa test. A subanalysis was performed to evaluate the influence of the interval between imaging and surgery. Results Out of 313 patients with LRRC treated during the study interval, 124 patients were selected. Interobserver agreement between the radiologists was fair (k = 0.28) using a two-tier grading system (mrTRG 1–2 versus mrTRG 3–5). For the lead radiologist, agreement with pTRG was moderate (k = 0.52; 95 per cent c.i. 0.36 to 0.68) when comparing good (mrTRG 1–2 and Mandard 1–2) and intermediate/poor responders (mrTRG 3–5 and Mandard 3–5), and the agreement was fair between the other abdominal radiologist and pTRG (k = 0.39; 95 per cent c.i. 0.22 to 0.56). A shorter interval (less than 7 weeks) between MRI and surgery resulted in an improved agreement (k = 0.69), compared with an interval more than 7 weeks (k = 0.340). For the lead radiologist, the positive predictive value for predicting good responders was 95 per cent (95 per cent c.i. 71 per cent to 99 per cent), whereas this was 56 per cent (95 per cent c.i. 44 per cent to 66 per cent) for the other radiologist. Conclusion This study showed that, in LRRC, the reproducibility of mrTRG among radiologists is limited and the agreement of mrTRG with pTRG is low. However, a shorter interval between MRI and surgery seems to improve this agreement and, if assessed by a dedicated radiologist, mrTRG could predict good responders.

Purpose This study investigated the long-term probability of developing a second cancer in a large pooled cohort of patients treated with surgery with or without radiotherapy (RT). Patients and Methods All second cancers diagnosed in patients included in the TME, PORTEC-1, and PORTEC-2 trials were analyzed. In the TME trial, patients with rectal cancer (n = 1,530) were randomly allocated to preoperative external-beam RT (EBRT; 25 Gy in five fractions) or no RT. In the PORTEC trials, patients with endometrial cancer were randomly assigned to postoperative EBRT (46 Gy in 2-Gy fractions) versus no RT (PORTEC-1; n = 714) or EBRT versus vaginal brachytherapy (VBT; PORTEC-2; n = 427). Results A total of 2,554 patients were analyzed (median follow-up, 13.0 years; range 1.8 to 21.2 years). No differences were found in second cancer probability between patients who were treated without RT (10- and 15-year rates, 15.8% and 26.5%, respectively) and those treated with EBRT (10- and 15-year rates, 15.4% and 25.6%, respectively) or VBT (10-year rate, 14.9%). In the individual trials, no significant differences were found between treatment arms. All cancer survivors had a higher risk of developing a second cancer compared with an age- and sex-matched general population. The standardized incidence ratio for any second cancer was 2.98 (95% CI, 2.82 to 3.14). Conclusion In this pooled trial cohort of > 2,500 patients with pelvic cancers, those who underwent EBRT or VBT had no higher probability of developing a second cancer than patients who were treated with surgery alone. However, patients with rectal or endometrial cancer had an increased probability of developing a second cancer compared with the general population.

The development of surgical site infection (SSI) can be a serious issue for patients, surgeons and healthcare providers due to the negative impact on post-operative morbidity and recovery time. SSIs are estimated to prolong the length of hospital stay and significantly increase the cost of care. Mandatory surveillance programmes and improvements in surgical and aseptic technique have led to a considerable reduction in the incidence of SSI in many countries and areas of surgery. However, this progress should not lead to complacency as significant challenges remain in the fight against SSI such as the increasing number of high-risk patients undergoing surgery and the growing problem of antibiotic resistance. In an ageing society, a growing number of patients with one or multiple co-morbidities will require surgery. The presence of conditions such as diabetes and obesity in patients has been demonstrated to increase the risk of SSI in many areas of surgery and therefore the rising prevalence of these conditions is of great concern to surgeons and healthcare providers. The World Health Organisation estimates that by 2030 the number of patients worldwide with diabetes will reach 366 million compared to the figure of 171 million in 2010. 1 The mainstay of SSI prevention in addition to strict aseptic surgical technique has been the use of systemic antibiotic prophylaxis. However, long-term administration of intravenous antibiotics may lead to a risk of antibiotic resistance and toxicity. The emergence of local antibiotic-eluting products such as resorbable gentamicin-containing collagen implants (GCCIs) which deliver high local concentrations of gentamicin with corresponding low serum levels may help to solve this issue. Local use of gentamicin delivers a bactericidal concentration that is much higher than that allowed by systemic injection, so antibiotic blood concentrations remain lowand reduce the chance of adverse effects while the local drug concentrations are kept high (above the minimal inhibitory concentration) for at least 48 h. In this way, resistance to antibiotics caused by low drug dosage is avoided and gentamicin behaves like a broad-spectrum antibiotic. Furthermore gentamicin-resistant bacteria are killed by the high local concentration of gentamicin. This supplement contains detailed overviews of the prophylactic and therapeutic use of GCCI in gastrointestinal, cardiac, vascular and orthopaedic surgery. The authors have carefully reviewed the data and rated the evidence to provide surgeons with a balanced view of the efficacy and cost-benefit of GCCI with specific focus in high-risk procedures and patients. Two recent randomised studies, failed to show a beneficial effect of GCCI in the prevention of SSI. 2,3 In the two studies the sponges were immersed in saline before use. This supplement contains new pharmacokinetic data concerning the elution of gentamicin from the collagen sponge. 4 These data clearly show that gentamicin is highly water-soluble and is easily rinsed from the collagen matrix by saline within seconds following immersion. This is an important piece of work by Lovering and colleagues as it provides a rationale for dry use of GCCI in line with the manufacturer’s recommendations. Minimising the development of SSI in high-risk patients is key to optimising patient outcome and controlling the increasing costs of healthcare. The development of antibiotic resistance, is still an issue of major concern despite the introduction of new antibiotics. Therefore the local route may be an important weapon in the war against SSI and antibiotic resistance.

Carcinoma of the rectum is a heterogeneous disease. At one end of the clinical spectrum, a small number of patients present with superficially invasive cancers who are well served by limited ­procedures, such as local excision or endocavitary irradiation. The great majority of patients with rectal cancer, however, have mobile but more deeply invasive tumors that require low anterior or abdominoperineal resection. At the other and less favorable end of the clinical spectrum, a subset of patients present with locally advanced tumors that are adherent or fixed to adjoining structures such as the sacrum, pelvic sidewalls, prostate, or bladder.

Since IORT using electron beams first became popular in the late 1970s and early 1980s, enthusiasm for the technique using conventional accelerators waned. The reasons for this are manyfold. The main factor was that IORT required considerable effort on the part of physicians, physicists, and therapists, as well as the loss of time on the linear accelerator for treating external beam irradiation therapy (EBRT) patients. While a dedicated facility alleviates some of these problems, the cost of building a shielded room for a low use (∼3–5 cases per week) linear accelerator was hard to justify in the face of declining reimbursements. The problem with reimbursements was in part related to the fact that in the USA there is no specific CPT code for this procedure, so the utilization costs were harder to recover. Finally, in some institutions, the lack of definite improvements in survival in certain disease-sites of interest made it hard to justify the additional departmental resources to carry out the procedure.