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Background and purpose: Intensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC). Materials and methods: The inter-fraction motion robustness was assessed for the initial twelve patients enrolled in the ReRad-II study. Patients with resectable LRRC were assessed for neoadjuvant IMPT (55 Gy(RBE)/44Fx) and unresectable recurrences for definitive IMPT (57.5–65 Gy(RBE)/ 46-52Fx). Target coverage and dose to OAR were assessed for robustly optimised three-field IMPT, on 12 plan computerized tomography (CT) scans (pCT) − and 47 repetitive control CT scans (cCTs) during the treatment. The target coverage and doses to OAR were re-calculated on each cCT and the mean dose ratio (pCT/cCT-ratio) and target coverage (V95%) was evaluated. Results: The target coverage was robust with a mean dose pCT/cCT-ratio of 1.00 (+/-1%). The V95% target coverage for every cCT were above the accepted worst-case scenario in the robust evaluation. Considerable variation in bladder-, bowel bag-, and bowel loop volume was observed. The OAR with the largest variation in ratio was the bladder (pCT/cCT-ratio: 1.3 (range: 0.5–4.7). Conclusions: IMPT for dose-escalated reirradiation of LRRC provided anatomically robust target coverage despite OAR changes. Inter-fraction motion resulted in OAR doses varying within clinically acceptable range.

Due to improvements in treatment for primary rectal cancer, the incidence of LRRC has decreased. However, 6-12% of patients will still develop a local recurrence. Treatment of patients with LRRC can be challenging, because of complex and heterogeneous disease presentation and scarce - often low-grade - data steering clinical decisions. Previous consensus guidelines have provided some direction regarding diagnosis and treatment, but no comprehensive guidelines encompassing all aspects of the clinical management of patients with LRRC are available to date. The treatment of LRRC requires a multidisciplinary approach and overarching expertise in all domains. This broad expertise is often limited to specific expert centres, with dedicated multidisciplinary teams treating LRRC. A comprehensive, narrative literature review was performed and used to develop the Dutch National Guideline for management of LRRC, in an attempt to guide decision making for clinicians, regarding the complete clinical pathway from diagnosis to surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: The aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status., Methods: Seventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0-1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately., Results: The rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005)., Conclusions: Narrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. Corresponding author Kay Uehara., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Prognostic features in locally recurrent rectal cancer (LRRC), beyond R0 surgery, are unknown., Aims: Aim of the present study was to evaluate the prognostic role of peripheral immune estimators, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on survival outcomes in LRRC patients., Methods: 184 LRRC patients treated at the National Cancer Institute of Milan (Italy) were included. Optimal cut-off values for NLR and PLR were determined. Kaplan-Meier curves and multivariate Cox analyses were used to assess the 5-yr overall survival (OS) according to NLR and PLR, also considering margins status., Results: NLR >3.9 (hazard ratio [HR] 3.96, P = 0.049), PLR >275 (HR 5.39, P = 0.002) and size on imaging (HR 1.36, P = 0.044) were associated to worse OS. R+ patients with NLR >3.9 showed a significantly lower 5-yr OS compared to NLR ≤3.9 (13.5% vs. 36.7%, P < 0.0001). Also PLR >275 was related with a lower 5-yr OS compared to PLR ≤275 in R+ patients (6.4% vs. 36.8%, P = 0.0003). Conversely, NLR and PLR were irrelevant in case of R0 surgery., Conclusion: NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Aim: To evaluate the clinical relevance of indeterminate lung nodules (ILN) in patients with locally recurrent rectal cancer (LRRC) treated in a tertiary referral centre., Methods: All patients with LRRC diagnosed between 2000 and 2017 were retrospectively reviewed. Reports of staging chest CT-scans were evaluated for ILN. Patients with distant metastases including lung metastases at time of LRRC diagnosis were excluded. Overall (OS), progression-free survival (PFS) and the cumulative incidence of lung metastases were compared between patients with and without ILN., Results: In total 556 patients with LRRC were treated during the study period. In the 243 patients eligible for analysis, 68 (28%) had ILN at LRRC diagnosis. Median OS was 37 months for both the patients with and without ILN (p = 0.37). Median PFS was 14 months for the patients with ILN and 16 months for patients without ILN (p = 0.80). After correction for potential confounding, ILN present at LRRC diagnosis was not associated with impaired OS or PFS (adjusted hazards ratio [95% confidence interval]: 0.81 [0.54-1.22] and 1.09 [0.75-1.59]). The 5-year cumulative incidence of lung metastases was 31% in patients with ILN and 28% in patients without ILN (p = 0.19)., Conclusion: Our study shows that ILN are present in roughly a quarter of patients with LRRC. No differences in OS, PFS, or the cumulative incidence of lung metastases were found between patients with and without ILN at LRRC diagnosis. These results suggest that ILN are of little to no clinical relevance in patients with LRRC., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: The majority of patients with locally recurrent rectal cancer (LRRC) present with extensive metastatic disease or an unresectable recurrence, and will be treated palliatively. Only a minority of patients will be eligible for potential cure by surgical treatment. The aim of this study is to evaluate the long-term outcome of surgical treatment and non-surgical treatment of patients with LRRC., Methods: All patients with LRRC referred to our tertiary institute between 2000 and 2015 were retrospectively analysed. Patients were discussed in a multidisciplinary tumour board (MDT) and eventually received curative surgical or non-surgical treatment. Overall survival (OS) was compared by resection margin status and non-surgical treatment., Results: A total of 447 patients were discussed in our MDT of which 193 patients underwent surgical treatment and 254 patients received non-surgical treatment. Surgically treated patients were significantly younger, received less neoadjuvant therapy for the primary tumour, had less metastasis at diagnosis and more central recurrences. The 5-year OS was 51% for R0-resections and 34% for R1-resections. Although numbers with R2-resections were too small to implicate prognostic significance, there was no difference in 5-year OS between R2-resections and non-surgical treatment (10% vs. 4%, p = 0.282). In a subgroup analysis the OS of R2-patients was even poorer compared to optimal palliative treated patients with combined chemotherapy and radiotherapy (22 vs 29 months, p = 0.413)., Conclusion: R2-resections do not result in a survival benefit compared to non-surgical treatment in this non-randomized series. Patients with a high chance on a R2-resection could be offered non-surgical treatment, without local resection., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The management of patients with locally recurrent rectal cancer (LRRC) is often complex and requires multidisciplinary input whereas only few patients are referred to a specialist centre. The aim of this study was to design a regional referral pathway for LRRC, in Nouvelle Aquitaine (South-West, France)., Methods: In 2016, we conducted with a Study Steering Committee (SC) a three phase mixed-methods study including identification of key factors, identification of key stakeholders and Delphi voting consensus. During three rounds of Delphi voting, a consensus was defined as favorable, if at least 80% of participating experts rate the factor, below or equal to 3/10 using a Likert scale, or consider it as "useful" using a binary scale (third round only). Finally, the SC drafted guidelines., Results: Among the 423 physicians involved in 29 regional digestive Multi-Disciplinary Team (MDT) meeting, 59 participants (from 26 MDT meeting) completed all three rounds of Delphi voting. Thirteen out of twenty initially selected factors reached a favorable consensus. All patients with a LRRC need to be included into a referral pathway. Patients with a central pelvic recurrence offered curative treatment in their local hospital and patients with unresectable metastatic disease were excluded of the referral. Key performance indicators were also agreed including the time to referral and completion of pelvic MRI-, CT-, PET-scan prior to MDT referral., Conclusion: The development of this referral pathway represents an innovative health service, which will improve the management of patients with LRRC in France., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Total pelvic exenteration (TPE) is a radical approach for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) in case of tumour invasion into the urogenitary tract. The aim of this study is to assess surgical and oncological outcomes of TPE for LARC and LRRC in elderly patients compared to younger patients., Methods: All patients who underwent TPE for LARC and LRRC between January 1990 and March 2017 were retrospectively analyzed. Patients aged <70 years were classified as younger and ≥70 years as elderly patients., Results: In total 126 patients underwent TPE, of whom 88 younger and 38 elderly patients. Elderly patients had a significantly higher number of ASA > II patients (p = 0.01). Indication for surgery LARC (n = 73) and LRRC (n = 53) did not differ significantly. The 30-day mortality rate was significantly higher (p = 0.01) in elderly (13%) compared to younger patients (3%). Elderly patients experienced more anastomotic leakage (p = 0.02). Median overall survival (OS) was 75 months [95%CI 37.1; 112.9] for elderly and 45 months [95%CI 22.4; 67.8] for younger patients (p = 0.77). The 5-year OS rate was 44% in both groups. Median disease specific survival (DSS) was 78 months [95%CI 69.1; 86.9] for elderly and 60 months [95%CI 36.6; 83.4] for younger patients (p = 0.34). The 5-year DSS rate was 57% and 49%, respectively., Conclusion: TPE is an invasive treatment for rectal cancer with high 30-day mortality in elderly patients. Oncological outcomes are similar in elderly and younger patients. Therefore, TPE should not be withheld because of high age only, but careful patient selection is needed., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres., Methods and Materials: Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied., Results: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection., Conclusions: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aims: The purpose of this study is to evaluate the outcome of abdominosacral resections (ASR) in patients with locally advanced or recurrent rectal cancer., Methods: From 1994 until 2012 patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) underwent a curative ASR and were enrolled in a database. The postoperative complication rates, predictive factors on oncological outcome and survival rates were registered., Results: Seventy-two patients with LRRC (mean age 63; 44 male, 28 female) and 14 patients with LARC (mean age 65; 6 male, 8 female) underwent ASR. R0 resection was achieved in 37 patients with LRRC and 11 patients with LARC. Twenty-seven patients underwent an R1 resection (3 in the LARC group). Eight patients had an R2 resection, compared to no patients in the LARC group. In respectively 26 and 1 patients of the LRRC and LARC groups a grade 3 or 4 complication occurred and the 30-days mortality rate was respectively 3% and 7%. The 5-years overall survival was 28% and 24% respectively., Conclusion: En bloc radical resection remains the primary goal in the treatment of dorsally located (recurrent) rectal cancer. After thorough patient selection, ASR is a safe procedure to perform, shows acceptable morbidity rates and leads to a good oncological outcome., (Copyright © 2014 Elsevier Ltd. All rights reserved.)