|
1
|
Wang W, Zhao R, Liang X, Liu M, Bai H, Ge J, Yao B, Zhi Z, He J. Efficacies of radiotherapy in rectal cancer patients treated with total mesorectal excision or other types of surgery: an updated meta-analysis. Oncol Rev 2025; 19:1567818. [PMID: 40376112 PMCID: PMC12078337 DOI: 10.3389/or.2025.1567818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/18/2025] [Indexed: 05/18/2025] Open
Abstract
Background An updated meta-analysis was conducted to evaluate the efficacy of radiotherapy in rectal cancer patients treated with total mesorectal excision (TME) or other types of surgery (non-TME-only). Methods The PubMed, Cochrane Library, and CNKI databases were searched. Data on overall survival (OS) were extracted. Results Hazard ratios (HRs) for OS associated with preoperative radiotherapy, preoperative long-course concurrent chemoradiotherapy (LCCRT), preoperative radiotherapy alone, and postoperative radiotherapy in patients treated with TME were 1.02 [95% CI: 0.92-1.14, P = 0.65], 1.04 [95% CI: 0.93-1.16, P = 0.47], 0.87 [95% CI: 0.61-1.25, P = 0.46], and 1.18 [95% CI: 0.91-1.52, P = 0.20], respectively. HRs for OS associated with preoperative radiotherapy, preoperative LCCRT, preoperative radiotherapy alone, preoperative long-course RT (LCRT), and preoperative short-course radiotherapy (SCRT) in patients treated with non-TME-only surgery were 0.85 [95% CI: 0.79-0.90, P < 0.00001], 0.77 [95% CI: 0.63-0.94, P = 0.009], 0.86 [95% CI: 0.80-0.92, P < 0.0001], 0.83 [95% CI: 0.73-0.95, P = 0.005], and 0.84 [95% CI: 0.77-0.91, P= <0.0001], respectively. The HR for postoperative radiotherapy in patients treated with non-TME-only surgery was 1.08 [95% CI: 0.84-1.39, P = 0.57]. Conclusion Preoperative radiotherapy, regardless of the regimen, improves the OS in patients treated with non-TME-only surgery, but not in those treated with TME. Postoperative radiotherapy does not improve OS. Advances in knowledge This meta-analysis will serve as a reference for decision-making in multidisciplinary approaches for rectal cancer patients.
Collapse
Affiliation(s)
- Wenshu Wang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Runyuan Zhao
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xi Liang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Manjun Liu
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Haiyan Bai
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Jianli Ge
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Binxi Yao
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Zheng Zhi
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Jianming He
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
- Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research (Hebei), Shijiazhuang, China
| |
Collapse
|
|
2
|
Shine RJ, Glyn T, Frizelle F. Pelvic exenteration: a review of current issues/controversies. ANZ J Surg 2022; 92:2822-2828. [PMID: 35490337 DOI: 10.1111/ans.17734] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 03/09/2022] [Accepted: 04/01/2022] [Indexed: 11/28/2022]
Abstract
Management of advanced or recurrent pelvic cancer has evolved dramatically over the past few decades. Patients who were previously considered inoperable are now candidates for potentially curative surgery and avoid suffering with intractable symptoms. Up to 10% of primary rectal cancers present with isolated advanced local disease and between 10% and 15% of patients develop localized recurrence following proctectomy. Advances in surgical technique, reconstruction and multidisciplinary involvement have led to a reduction in mortality and morbidity and culminated in higher R0 resection rates with superior longer-term survival outcomes. Recent studies boast over 50% 5-year survival for rectal with an R0 resection. Exenteration has cemented itself as an important treatment option for advanced primary/recurrent pelvic tumours, however, there are still a few controversies. This review will discuss some of these issues, including: limitations of resection and the approach to high/wide tumours; the role of acute exenteration; re-exenteration; exenteration in the setting of metastatic disease and palliation; the role of radiotherapy (including intra-operative and re-irradiation); management of the empty pelvis; and the impact on quality of life and function.
Collapse
Affiliation(s)
- Rebecca J Shine
- Department of General Surgery, Christchurch Hospital, Christchurch, New Zealand
| | - Tamara Glyn
- Department of General Surgery, Christchurch Hospital, Christchurch, New Zealand.,Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Frank Frizelle
- Department of General Surgery, Christchurch Hospital, Christchurch, New Zealand.,Department of Surgery, University of Otago, Christchurch, New Zealand
| |
Collapse
|
|
3
|
Fahy MR, Kelly ME, Power Foley M, Nugent TS, Shields CJ, Winter DC. The role of intraoperative radiotherapy in advanced rectal cancer: a meta-analysis. Colorectal Dis 2021; 23:1998-2006. [PMID: 33905599 DOI: 10.1111/codi.15698] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/13/2021] [Accepted: 04/15/2021] [Indexed: 12/12/2022]
Abstract
AIM Patients with locally advanced and locally recurrent rectal cancer (LARC/LRRC) experience higher rates of local recurrence (LR) and poorer overall survival than patients with primary rectal cancer restricted to the mesorectum despite improved neoadjuvant treatment regimens and radical surgical procedures. Intraoperative radiotherapy (IORT) has been suggested as an adjunctive tool in the surgical management of these challenging cases. However, clear evidence regarding the oncological benefit of IORT is sparse. The aim of this review was to update this evidence in the era of standardized neoadjuvant radiotherapy administration. METHOD A systematic review of patients who received IORT as part of multimodal treatment for advanced rectal cancer from 2000 to 2020 and an analysis of IORT and surgery/external beam radiotherapy (EBRT) groups was performed. The primary endpoint was the rate of LR between the two groups. RESULTS Seven papers met the predefined criteria. LR was reduced by the addition of IORT when compared with the surgery/EBRT alone group (14.7% vs. 21.4%; OR 0.55, 95% CI 0.27-1.14; p = 0.11). There was no increase in reported genitourinary morbidity, wound issues, pelvic collections or anastomotic leak in those patients who received IORT. Notably, there was no survival difference between the two groups. CONCLUSION The addition of IORT to current treatment strategies in the management of patients with LARC/LRRC is associated with a lower rate of locoregional recurrence without increased morbidity. However, this marks a highly selective group of patients, with heterogeneity regarding indications, prior neoadjuvant treatments and/or IORT dosing.
Collapse
Affiliation(s)
- Matthew R Fahy
- University College Dublin, Belfield, Dublin 4, Ireland.,Centre for Colorectal Disease, St Vincent's Hospital, Dublin, Ireland
| | - Michael E Kelly
- University College Dublin, Belfield, Dublin 4, Ireland.,Centre for Colorectal Disease, St Vincent's Hospital, Dublin, Ireland
| | | | - Timothy S Nugent
- Department of Surgery, Trinity College Dublin, College Green, Dublin, Ireland
| | | | - Des C Winter
- University College Dublin, Belfield, Dublin 4, Ireland.,Centre for Colorectal Disease, St Vincent's Hospital, Dublin, Ireland
| |
Collapse
|
|
4
|
Christou N, Meyer J, Combescure C, Balaphas A, Robert-Yap J, Buchs NC, Ris F. Prevalence of Metastatic Lateral Lymph Nodes in Asian Patients with Lateral Lymph Node Dissection for Rectal Cancer: A Meta-analysis. World J Surg 2021; 45:1537-1547. [PMID: 33543333 PMCID: PMC8026473 DOI: 10.1007/s00268-021-05956-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2021] [Indexed: 12/24/2022]
Abstract
IMPORTANCE Rectal cancers occupy the eighth position worldwide for new cases and deaths for both men and women. These cancers have a high tendency to form metastases in the mesorectum but also in the lateral lymph nodes. The therapeutic approach for the involved lateral lymph nodes remains controversial. OBJECTIVE We performed a systematic review and meta-analysis to assess the prevalence of metastatic lateral lymph nodes in patients with lateral lymph node dissection (LLND) for rectal cancer, which seems to be a fundamental and necessary criterion to discuss any possible indications for LLND. METHODS Data sources-study selection-data extraction and synthesis-main outcome and measures. We searched MEDLINE, EMBASE and COCHRANE from November 1, 2018, to November 19, 2018, for studies reporting the presence of metastatic lateral lymph nodes (iliac, obturator and middle sacral nodes) among patients undergoing rectal surgery with LLND. Pooled prevalence values were obtained by random effects models, and the robustness was tested by leave-one-out sensitivity analyses. Heterogeneity was assessed using the Q-test, quantified based on the I2 value and explored by subgroup analyses. RESULTS Our final analysis included 31 studies from Asian countries, comprising 7599 patients. The pooled prevalence of metastatic lateral lymph nodes was 17.3% (95% CI: 14.6-20.5). The inter-study variability (heterogeneity) was high (I2 = 89%). The pooled prevalence was, however, robust and varied between 16.6% and 17.9% according to leave-one-out sensitivity analysis. The pooled prevalence of metastatic lymph nodes was not significantly different when pooling only studies including patients who received neoadjuvant treatment or those without neoadjuvant treatment (p = 0.44). Meta-regression showed that the pooled prevalence was associated with the sample size of studies (p < 0.05), as the prevalence decreased when the sample size increased. CONCLUSION The pooled prevalence of metastatic lateral lymph nodes was 17.3% among patients who underwent rectal surgery with LLND in Asian countries. Further studies are necessary to determine whether this finding could impact the therapeutic strategy (total mesorectal excision with LLND versus total mesorectal excision with neoadjuvant radiochemotherapy).
Collapse
Affiliation(s)
- Niki Christou
- Digestive Surgery Department, University Hospital of Limoges, 2 Avenue Martin Luther King, 87042, Limoges, France.
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 41211, Geneva 14, Switzerland.
| | - Jeremy Meyer
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 41211, Geneva 14, Switzerland
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206, Geneva, Switzerland
| | - Christophe Combescure
- Division of Clinical Epidemiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland
| | - Alexandre Balaphas
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 41211, Geneva 14, Switzerland
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206, Geneva, Switzerland
| | - Joan Robert-Yap
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 41211, Geneva 14, Switzerland
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206, Geneva, Switzerland
| | - Nicolas C Buchs
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 41211, Geneva 14, Switzerland
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206, Geneva, Switzerland
| | - Frédéric Ris
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil, 41211, Geneva 14, Switzerland
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206, Geneva, Switzerland
| |
Collapse
|
|
5
|
Dijkstra EA, Mul VEM, Hemmer PHJ, Havenga K, Hospers GAP, Kats-Ugurlu G, Beukema JC, Berveling MJ, El Moumni M, Muijs CT, van Etten B. Clinical selection strategy for and evaluation of intra-operative brachytherapy in patients with locally advanced and recurrent rectal cancer. Radiother Oncol 2021; 159:91-97. [PMID: 33741470 DOI: 10.1016/j.radonc.2021.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 03/05/2021] [Accepted: 03/08/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND PURPOSE A radical resection of locally advanced rectal cancer (LARC) or recurrent rectal cancer (RRC) can be challenging. In case of increased risk of an R1 resection, intra-operative brachytherapy (IOBT) can be applied. We evaluated the clinical selection strategy for IOBT. MATERIALS AND METHODS Between February 2007 and May 2018, 132 LARC/RRC patients who were scheduled for surgery with IOBT standby, were evaluated. By intra-operative inspection of the resection margin and MR imaging, it was determined whether a resection was presumed to be radical. Frozen sections were taken on indication. In case of a suspected R1 resection, IOBT (1 × 10 Gy) was applied. Histopathologic evaluation, treatment and toxicity data were collected from medical records. RESULTS Tumour was resected in 122 patients. IOBT was given in 42 patients of whom 54.8% (n = 23) had a histopathologically proven R1 resection. Of the 76 IOBT-omitted R0 resected patients, 17.1% (n = 13) had a histopathologically proven R1 resection. In 4 IOBT-omitted patients, a clinical R1/2 resection was seen. In total, correct clinical judgement occurred in 72.6% (n = 88) of patients. In LARC, 58.3% (n = 14) of patients were overtreated (R0, with IOBT) and 10.9% (n = 5) were undertreated (R1, without IOBT). In RRC, 26.5% (n = 9) of patients were undertreated. CONCLUSION In total, correct clinical judgement occurred in 72.6% (n = 88). However, in 26.5% (n = 9) RRC patients, IOBT was unjustifiedly omitted. IOBT is accompanied by comparable and acceptable toxicity. Therefore, we recommend IOBT to all RRC patients at risk of an R1 resection as their salvage treatment.
Collapse
Affiliation(s)
- Esmée A Dijkstra
- University of Groningen, University Medical Centre Groningen, Department of Medical Oncology, the Netherlands
| | - Véronique E M Mul
- University of Groningen, University Medical Centre Groningen, Department of Radiation Oncology, the Netherlands
| | - Patrick H J Hemmer
- University of Groningen, University Medical Centre Groningen, Department of Surgery, the Netherlands
| | - Klaas Havenga
- University of Groningen, University Medical Centre Groningen, Department of Surgery, the Netherlands
| | - Geke A P Hospers
- University of Groningen, University Medical Centre Groningen, Department of Medical Oncology, the Netherlands
| | - Gursah Kats-Ugurlu
- University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, the Netherlands
| | - Jannet C Beukema
- University of Groningen, University Medical Centre Groningen, Department of Radiation Oncology, the Netherlands
| | - Maaike J Berveling
- University of Groningen, University Medical Centre Groningen, Department of Radiation Oncology, the Netherlands
| | - Mostafa El Moumni
- University of Groningen, University Medical Centre Groningen, Department of Surgery, the Netherlands
| | - Christina T Muijs
- University of Groningen, University Medical Centre Groningen, Department of Radiation Oncology, the Netherlands
| | - Boudewijn van Etten
- University of Groningen, University Medical Centre Groningen, Department of Surgery, the Netherlands.
| |
Collapse
|
|
6
|
Masaki T, Matsuoka H, Kishiki T, Kojima K, Tonari A, Aso N, Beniya A, Iioka A, Wakamatsu T, Sunami E. Site-specific risk factors for local recurrence after rectal cancer surgery. Surg Oncol 2021; 37:101540. [PMID: 33714843 DOI: 10.1016/j.suronc.2021.101540] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/16/2021] [Accepted: 03/02/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Quite few studies examined risk factors for local recurrence after rectal cancer surgery with respect to local recurrence sites. METHODS Local recurrence sites were categorized into axial, anterior, posterior, and lateral (pelvic sidewall), and axial, anterior, and posterior type were combined as the "other" type of local recurrence. Among 76 patients enrolled into our prospective randomized controlled trial to determine the indication for pelvic autonomic nerve preservation (PANP) in patients with advanced lower rectal cancer (UMIN000021353), multivariate analyses were conducted to elucidate risk factors for either lateral or the "other" type of local recurrence. RESULTS Univariate analyses showed that tumor distance from the anal verge was significantly (p = 0.017), and type of operation (sphincter preserving operation (SPO) vs. abdominoperineal resection (APR)) was marginally (p = 0.065) associated with pelvic sidewall recurrence. Multivariate analysis using these two parameters showed that tumor distance from the anal verge was significantly and independently correlated with pelvic sidewall recurrence (p = 0.017). As for the "other" type of local recurrence, univariate analyses showed that depth of tumor invasion (p = 0.011), radial margin status (p < 0.001), and adjuvant chemotherapy (p = 0.037) were significantly associated, and multivariate analysis using these three parameters revealed that depth of tumor invasion (p = 0.004) and radial margin status (p < 0.001) were significantly and independently correlated with the "other" type of local recurrence. CONCLUSION Risk factors for local recurrence after rectal cancer surgery were totally different with respect to the intra-pelvic recurrent sites. Site-specific probability of local recurrence can be inferred using these risk factors. TRIAL REGISTRATION NUMBER UMIN000021353.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Aiko Iioka
- Department of Surgery, Kyorin University, Japan
| | | | - Eiji Sunami
- Department of Surgery, Kyorin University, Japan
| |
Collapse
|
|
7
|
Liu B, Ge L, Wang J, Chen YQ, Ma SX, Ma PL, Zhang YQ, Yang KH, Cai H. Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis. World J Gastrointest Oncol 2021; 13:69-86. [PMID: 33510850 PMCID: PMC7805273 DOI: 10.4251/wjgo.v13.i1.69] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/06/2020] [Accepted: 12/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.
AIM To evaluate the value of IORT for patients with rectal cancer.
METHODS We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.
RESULTS In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000).
CONCLUSION The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.
Collapse
Affiliation(s)
- Bin Liu
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jing Wang
- Gansu University of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Ya-Qiong Chen
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Pei-Lan Ma
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Yun-Qiang Zhang
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Ke-Hu Yang
- Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
8
|
Joechle K, Gkika E, Grosu AL, Lang SA, Fichtner-Feigl S. Intraoperative Strahlentherapie – Indikationen und Optionen in der Viszeralchirurgie. Chirurg 2020; 91:743-754. [DOI: 10.1007/s00104-020-01179-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Zusammenfassung
Hintergrund
Die intraoperative Strahlentherapie (IORT) ermöglicht durch die chirurgische Exposition des Tumors und des Tumorbetts eine hohe Präzision, welche eine hohe Strahlendosis im Bereich des Tumors zulässt und gleichzeitig gesundes Gewebe als den dosislimitierenden Faktor vor Strahlung schützt. Aus diesem Grund bietet die IORT besonders dann einen Vorteil, wenn die lokale Tumorkontrolle das Langzeitüberleben entscheidend beeinflusst und Funktionserhalt ermöglicht.
Ziel der Arbeit
Die in dieser Übersichtsarbeit aufgearbeiteten Erkenntnisse aus der Literaturrecherche erlauben einen evidenzbasierten Umgang hinsichtlich Indikationen und Therapieoptionen der IORT für intraabdominelle Tumoren.
Ergebnisse und Schlussfolgerung
Die Effektivität der IORT kann anhand der vorhandenen Evidenzlage nicht abschließend beurteilt werden, jedoch ist die IORT als Ergänzung der multimodalen Therapie bei (Rezidiv‑)Rektumkarzinomen und Sarkomen aktiv im klinischen Alltag etabliert. Magen- und Pankreaskarzinome stellen weitere Indikationen dar; ergänzende Studien sind jedoch notwendig, um die Rolle der IORT hier klar zu definieren. Ein wesentlicher Faktor, damit für Patienten mit primärem Karzinom und insbesondere für Patienten mit lokalem Rezidiv verbesserte lokale Rezidiv- und Überlebensraten erreicht werden können, scheint die Patientenselektion zu sein.
Collapse
|
|
9
|
Masaki T, Matsuoka H, Kishiki T, Kojima K, Aso N, Beniya A, Tonari A, Takayama M, Abe N, Sunami E. Intraoperative radiotherapy for resectable advanced lower rectal cancer-final results of a randomized controlled trial (UMIN000021353). Langenbecks Arch Surg 2020; 405:247-254. [PMID: 32347365 DOI: 10.1007/s00423-020-01875-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/30/2020] [Indexed: 01/24/2023]
Abstract
AIM Pelvic autonomic nerve preservation (PANP) is useful to preserve voiding and sexual function after rectal cancer surgery. The aim of this study was to investigate the benefit of intraoperative radiotherapy (IORT) to have complete PANP without affecting oncological outcomes. METHODS Patients undergoing potentially curative resection of the rectum were included. They were randomized to intraoperative radiotherapy of the completely preserved bilateral pelvic nerve plexuses (IORT group) or the control group without IORT, but with limited nerve preservation. The primary endpoint was pelvic sidewall recurrence. Moreover, patients' clinicopathologic parameters, postoperative complications, voiding function, and other oncologic outcomes were compared. RESULTS From 79 patients, three were excluded from analysis, resulting in 38 patients in each group. Patients' demographic and pathological parameters were well balanced between the two groups. The trial was terminated prematurely in July 2017, because distant metastasis-free survivals were found to be significantly worse in the IORT group compared to the control group (odds ratio 2.554; 95% CI, 1.041 ~ 6.269; p = 0.041). Neither overall survival nor pelvic sidewall recurrence did differ between the two groups (overall survival: odds ratio 1.264; 95% CI, 0.523~3.051; p = 0.603/pelvic sidewall recurrence; odds ratio 1.350; 95% CI, 0.302~6.034; p = 0.694). Postoperative complications did not differ between the groups; however, the urinary function was significantly better in the IORT group in the short and long term. CONCLUSION With the aid of IORT, complete PANP can be done without increase of pelvic sidewall recurrence; however, IORT may increase the incidence of distant metastases. Therefore, IORT cannot be recommended as a standard therapy to compensate less radical resection for advanced lower rectal cancer.
Collapse
Affiliation(s)
- Tadahiko Masaki
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan.
| | - Hiroyoshi Matsuoka
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Tomokazu Kishiki
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Koichiro Kojima
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Nobuyoshi Aso
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Ayumi Beniya
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Ayako Tonari
- Department of Radiation Oncology, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Makoto Takayama
- Department of Radiation Oncology, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Nobutsugu Abe
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| | - Eiji Sunami
- Department of Surgery, Kyorin University Hospital, 6-20-2, Shinkawa, Mitaka City, Tokyo, 181-8611, Japan
| |
Collapse
|
|
10
|
Potemin S, Kübler J, Uvarov I, Wenz F, Giordano F. Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy. Radiat Oncol 2020; 15:11. [PMID: 31924250 PMCID: PMC6954580 DOI: 10.1186/s13014-020-1458-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 01/05/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Neoadjuvant external-beam radiotherapy (EBRT) with concomitant chemotherapy is the current standard-of-care for locally-advanced rectal cancer. Intraoperative radiotherapy (IORT) is to date only recommended for pelvic recurrences or incompletely resectable tumors. We here report on patients with stage II/III rectal cancer that were treated with IORT in a regional Russian university center due to limited access to EBRT. METHODS We retrospectively analyzed data from patients that were diagnosed with locally-advanced rectal cancer and underwent surgery from December 2012 to October 2016 at a regional oncological center in Russia (Krasnodar). During this period, access to EBRT was limited due to a temporary lack of a sufficient number of EBRT facilities. Patients unable to travel to a distant radiotherapy site received IORT alone, those that could travel received neoadjuvant external beam (chemo-) radiotherapy. Factors of interest were tumor stage, tumor differentiation, resection status, surgery type and neoadjuvant or adjuvant chemotherapy. We assessed local progression-free survival (L-PFS), PFS and overall survival (OS). RESULTS A total of 172 patients were included in this analysis. Of those, 92 (53.5%) were treated with IORT alone (median dose: 15 Gy [8.4-17 Gy]) and 80 (46.5%) received both neoadjuvant EBRT (median dose: 50.4 Gy [40-50.4 Gy]) and IORT (median dose: 15 Gy [15-17 Gy]). The median age was 65 years [33-82]. The median follow-up was 23 months [0-63 months]. The incidence of toxicity was low in both groups with an overall complication rate of 5.4%. Local PFS at 4 years was comparable with 59.4% in the IORT group and 65.4% in the IORT/EBRT group (p = 0.70). Similarly, there was no difference in OS or PFS (p = 0.66, p = 0.51, respectively). CONCLUSIONS IORT is a valuable option for patients with locally-advanced rectal cancer in the absence of access to EBRT.
Collapse
Affiliation(s)
- Sergey Potemin
- Department of Colorectal Surgery, Regional Oncological Center of Krasnodar, Krasnodar, Russia
| | - Jens Kübler
- Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Ivan Uvarov
- Department of Colorectal Surgery, Regional Oncological Center of Krasnodar, Krasnodar, Russia
| | - Frederik Wenz
- Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Frank Giordano
- Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
| |
Collapse
|
|
11
|
Tom MC, Joshi N, Vicini F, Chang AJ, Hong TS, Showalter TN, Chao ST, Wolden S, Wu AJ, Martin D, Husain Z, Badiyan SN, Kolar M, Sherertz T, Mourtada F, Cohen GN, Shah C. The American Brachytherapy Society consensus statement on intraoperative radiation therapy. Brachytherapy 2019; 18:242-257. [PMID: 31084904 DOI: 10.1016/j.brachy.2019.01.015] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Accepted: 01/30/2019] [Indexed: 12/12/2022]
Abstract
PURPOSE Although radiation therapy has traditionally been delivered with external beam or brachytherapy, intraoperative radiation therapy (IORT) represents an alternative that may shorten the course of therapy, reduce toxicities, and improve patient satisfaction while potentially lowering the cost of care. At this time, there are limited evidence-based guidelines to assist clinicians with patient selection for IORT. As such, the American Brachytherapy Society presents a consensus statement on the use of IORT. METHODS Physicians and physicists with expertise in intraoperative radiation created a site-directed guideline for appropriate patient selection and utilization of IORT. RESULTS Several IORT techniques exist including radionuclide-based high-dose-rate, low-dose-rate, electron, and low-energy electronic. In breast cancer, IORT as monotherapy should only be used on prospective studies. IORT can be considered in the treatment of sarcomas with close/positive margins or recurrent sarcomas. IORT can be considered in conjunction with external beam radiotherapy for retroperitoneal sarcomas. IORT can be considered for colorectal malignancies with concern for positive margins and in the setting of recurrent gynecologic cancers. For thoracic, head and neck, and central nervous system malignancies, utilization of IORT should be evaluated on a case-by-case basis. CONCLUSIONS The present guidelines provide clinicians with a summary of current data regarding IORT by treatment site and guidelines for the appropriate patient selection and safe utilization of the technique. High-dose-rate, low-dose-rate brachytherapy methods are appropriate when IORT is to be delivered as are electron and low-energy based on the clinical scenario.
Collapse
Affiliation(s)
- Martin C Tom
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland, OH
| | - Nikhil Joshi
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland, OH
| | - Frank Vicini
- 21st Century Oncology, Michigan Healthcare Professionals, Farmington Hills, MI
| | | | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Timothy N Showalter
- Department of Radiation Oncology, University of Virginia, Charlottesville, VA
| | - Samuel T Chao
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland, OH
| | - Suzanne Wolden
- Departments of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Abraham J Wu
- Departments of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Douglas Martin
- Department of Radiation Oncology, Ohio State University, Columbus, OH
| | - Zain Husain
- Department of Therapeutic Radiology, Yale University, New Haven, CT
| | - Shahed N Badiyan
- Department of Radiation Oncology, Washington University, St. Louis, MO
| | - Matthew Kolar
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland, OH
| | - Tracy Sherertz
- Department of Radiation Oncology, Kaiser Capitol Hill, Seattle, WA
| | - Firas Mourtada
- Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE
| | - Gilad N Cohen
- Department Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Chirag Shah
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland, OH.
| |
Collapse
|
|
12
|
Christou N, Meyer J, Toso C, Ris F, Buchs NC. Lateral lymph node dissection for low rectal cancer: Is it necessary? World J Gastroenterol 2019; 25:4294-4299. [PMID: 31496614 PMCID: PMC6710187 DOI: 10.3748/wjg.v25.i31.4294] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 06/19/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Rectal cancer constitutes a major public health issue. Total mesorectal excision has remained the gold standard treatment for mid and low rectal tumors since its introduction in the late 1980s. Removal of all lymph nodes located in the mesorectum has indeed improved pathological and oncological outcomes. However, when cancer spreads to the lateral lymph nodes (located along the iliac and obturator arteries) Western and Japanese practices differ. Where the Western guidelines consider this condition as an advanced form of the disease and use neoadjuvant radiochemotherapy liberally, the Japanese guidelines define it as a local disease and proceed to lateral lymph node dissection with or without neoadjuvant treatment. Herein, we review the current literature regarding both therapeutic strategies, with the aim of contributing to potential improvements in treatment and outcome for patients with low and mid rectal cancer.
Collapse
Affiliation(s)
- Niki Christou
- Service de Chirurgie Digestive, Endocrinienne et Générale, CHU de Limoges, Limoges Cedex 87042, France
- Division of Digestive Surgery, University Hospitals of Geneva, Genève 1211, Switzerland
- Unit of Surgical Research, University of Geneva, Genève 1206, Switzerland
| | - Jeremy Meyer
- Division of Digestive Surgery, University Hospitals of Geneva, Genève 1211, Switzerland
- Unit of Surgical Research, University of Geneva, Genève 1206, Switzerland
| | - Christian Toso
- Division of Digestive Surgery, University Hospitals of Geneva, Genève 1211, Switzerland
- Unit of Surgical Research, University of Geneva, Genève 1206, Switzerland
| | - Frédéric Ris
- Division of Digestive Surgery, University Hospitals of Geneva, Genève 1211, Switzerland
- Unit of Surgical Research, University of Geneva, Genève 1206, Switzerland
| | - Nicolas Christian Buchs
- Division of Digestive Surgery, University Hospitals of Geneva, Genève 1211, Switzerland
- Unit of Surgical Research, University of Geneva, Genève 1206, Switzerland
| |
Collapse
|
|
13
|
Tam SY, Wu VWC. A Review on the Special Radiotherapy Techniques of Colorectal Cancer. Front Oncol 2019; 9:208. [PMID: 31001474 PMCID: PMC6454863 DOI: 10.3389/fonc.2019.00208] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 03/11/2019] [Indexed: 12/23/2022] Open
Abstract
Colorectal cancer is one of the commonest cancers worldwide. Radiotherapy has been established as an indispensable component of treatment. Although conventional radiotherapy provides good local control, radiotherapy treatment side-effects, local recurrence and distant metastasis remain to be the concerns. With the recent technological advancements, various special radiotherapy treatment options have been offered. This review article discusses the recently-developed special radiotherapy treatment modalities for various conditions of colorectal cancer ranging from early stage, locally advanced stage, recurrent, and metastatic diseases. The discussion focuses on the areas of feasibility, local control, and survival benefits of the treatment modalities. This review also provides accounts of the future direction in radiotherapy of colorectal cancer with emphasis on the coming era of personalized radiotherapy.
Collapse
Affiliation(s)
- Shing Yau Tam
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Vincent W C Wu
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| |
Collapse
|
|
14
|
Significance, diagnosis and treatment of lateral lymph nodes in rectal cancer: A systematic review. INTERNATIONAL JOURNAL OF SURGERY OPEN 2019. [DOI: 10.1016/j.ijso.2019.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
15
|
Mahvi DA, Liu R, Grinstaff MW, Colson YL, Raut CP. Local Cancer Recurrence: The Realities, Challenges, and Opportunities for New Therapies. CA Cancer J Clin 2018; 68:488-505. [PMID: 30328620 PMCID: PMC6239861 DOI: 10.3322/caac.21498] [Citation(s) in RCA: 202] [Impact Index Per Article: 28.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 08/20/2018] [Accepted: 08/27/2018] [Indexed: 12/20/2022] Open
Abstract
Locoregional recurrence negatively impacts both long-term survival and quality of life for several malignancies. For appropriate-risk patients with an isolated, resectable, local recurrence, surgery represents the only potentially curative therapy. However, oncologic outcomes remain inferior for patients with locally recurrent disease even after macroscopically complete resection. Unfortunately, these operations are often extensive, with significant perioperative morbidity and mortality. This review highlights selected malignancies (mesothelioma, sarcoma, lung cancer, breast cancer, rectal cancer, and peritoneal surface malignancies) in which surgical resection is a key treatment modality and local recurrence plays a significant role in overall oncologic outcome with regard to survival and quality of life. For each type of cancer, the current, state-of-the-art treatment strategies and their outcomes are assessed. The need for additional therapeutic options is presented given the limitations of the current standard therapies. New and emerging treatment modalities, including polymer films and nanoparticles, are highlighted as potential future solutions for both prevention and treatment of locally recurrent cancers. Finally, the authors identify additional clinical and research opportunities and propose future research strategies based on the various patterns of local recurrence among the different cancers.
Collapse
Affiliation(s)
- David A Mahvi
- Postdoctoral Research Fellow, Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Rong Liu
- Instructor in Surgery, Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Mark W Grinstaff
- Professor of Translational Research, Biomedical Engineering, Chemistry, Materials Science and Engineering, and Medicine, Department of Chemistry, Boston University, Boston, MA
| | - Yolonda L Colson
- Michael A. Bell Family Distinguished Chair in Healthcare Innovation and Professor of Surgery, Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Chandrajit P Raut
- Associate Professor of Surgery, Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| |
Collapse
|
|
16
|
Pilar A, Gupta M, Ghosh Laskar S, Laskar S. Intraoperative radiotherapy: review of techniques and results. Ecancermedicalscience 2017; 11:750. [PMID: 28717396 PMCID: PMC5493441 DOI: 10.3332/ecancer.2017.750] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Indexed: 12/14/2022] Open
Abstract
Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community. Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise. IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers). This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.
Collapse
Affiliation(s)
- Avinash Pilar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Meetakshi Gupta
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Sarbani Ghosh Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Siddhartha Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| |
Collapse
|
|
17
|
Intraoperative high-dose-rate brachytherapy: An American Brachytherapy Society consensus report. Brachytherapy 2017; 16:446-465. [DOI: 10.1016/j.brachy.2017.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Revised: 12/19/2016] [Accepted: 01/02/2017] [Indexed: 11/22/2022]
|
|
18
|
Holman FA, Haddock MG, Gunderson LL, Kusters M, Nieuwenhuijzen GAP, van den Berg HA, Nelson H, Rutten HJT. Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven. J Gastrointest Oncol 2016; 7:903-916. [PMID: 28078113 DOI: 10.21037/jgo.2016.07.01] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. METHODS In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. RESULTS A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. CONCLUSIONS An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and prognostic factor in the treatment of T4 rectal cancer for all outcome parameters. IOERT can reduce the LR rate effectively, especially in R+ resected patients.
Collapse
Affiliation(s)
- Fabian A Holman
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | - Miranda Kusters
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | - Heidi Nelson
- Department of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
| | - Harm J T Rutten
- ; GROW: School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| |
Collapse
|
|
19
|
Albandar MH, Cho MS, Bae SU, Kim NK. Surgical management of extra-regional lymph node metastasis in colorectal cancer. Expert Rev Anticancer Ther 2016; 16:503-513. [PMID: 26950286 DOI: 10.1586/14737140.2016.1162718] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
One of the major problems in rectal cancer surgery is local recurrence, found in an average of 21% to 46% cases in 1990. However, the advent of chemo-radiotherapy (CRT) and total mesorectal excision (TME) improve local control and enhances survival rates in colorectal cancer (CRC). Regional lymph node involvement is determined to be an independent prognostic factor in local recurrence; however, extra-regional lymph node (ERLN) metastasis has a higher recurrence rate (up to 58.1%). Lack of supportive data in management of ERLN metastasis in CRC has added further strain and challenges to structure a unique treatment strategy. ERLN refers to extra-mesenteric involvement either in the para-aortic lymph node (PALN) or the lateral pelvic lymph node (LPLN). Treatment of ERLN metastasis is challenging because of the shortage of the resources. Here, we will outline and summarize approaches and management of ERLN metastasis. We also aim to clarify the role of surgical intervention in CRC.
Collapse
Affiliation(s)
- Mahdi H Albandar
- a Department of Surgery, College of Medicine , Yonsei University , Seoul , Korea
| | - Min Soo Cho
- a Department of Surgery, College of Medicine , Yonsei University , Seoul , Korea
| | - Sung Uk Bae
- a Department of Surgery, College of Medicine , Yonsei University , Seoul , Korea
| | - Nam Kyu Kim
- a Department of Surgery, College of Medicine , Yonsei University , Seoul , Korea
| |
Collapse
|
|
20
|
Complications associated with postoperative adjuvant radiation therapy for advanced rectal cancer. Int Surg 2015; 99:100-5. [PMID: 24670017 DOI: 10.9738/intsurg-d-13-00200.1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Preoperative management of advanced rectal cancer often includes chemoradiotherapy, but little is known about the late complications of radiotherapy. However, these are usually serious, making determination of the characteristics of late complications after radiation therapy critical. Accordingly, we investigated the complications occurring after adjuvant pelvic radiation therapy in patients with advanced rectal cancer. We enrolled 34 consecutive patients with TNM stage III rectal cancer who had undergone curative surgery with adjuvant pelvic radiation therapy. Data on the type of complication/organ involved, the number of complications, the phase of onset, and the treatments used were reviewed. Patients who experienced gut complications or edema were less likely to have their complications resolved than those with complications due to infection. Similarly, patients with multiple complications and late-onset complications were also less likely to have their complications resolved than those with single complications and those with early-onset complications, respectively. Adjuvant radiation therapy in patients with resected advanced rectal cancer was associated with various complications, characterized by late onset and impaired resolution. Therefore, patients indicated for radiation therapy should be selected with great caution.
Collapse
|
|
21
|
Klink CD, Binnebösel M, Holy R, Neumann UP, Junge K. Influence of intraoperative radiotherapy (IORT) on perioperative outcome after surgical resection of rectal cancer. World J Surg 2014; 38:992-6. [PMID: 24178183 DOI: 10.1007/s00268-013-2313-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intraoperative radiotherapy (IORT) for locally advanced or recurrent rectal cancer as an integral part of multimodal treatment might be an option to reduce local cancer recurrence. The aim of the present study was to determine the influence of IORT on the postoperative outcome and complications rates in the treatment of patients with adenocarcinoma of the rectum in comparison to patients with rectum resection only. METHODS A total of 162 patients underwent operation for International Union against Cancer stage III/IV rectal cancer or recurrent rectal cancer at our surgical department between 2004 and 2012. They were divided into two groups depending on whether they received IORT or not. General patient details, tumor, and operation details, as well as perioperative major and minor complications, were registered and compared. RESULTS Of the 162 patients treated for stage III/IV rectal cancer, 52 underwent rectal resection followed by IORT. Complication rates were similar in the two groups. Operative time was significantly longer in the IORT group (248 ± 84 vs 177 ± 68 min; p < 0.001). No significant differences were found concerning anastomotic leakage rate, hospital stay, or wound infection rate. CONCLUSIONS Intraoperative radiotherapy appears to be a safe treatment option in patients with locally advanced or recurrent rectal cancer with acceptable complication rates. The effect on local recurrence rate has to be estimated in long-term follow-up.
Collapse
Affiliation(s)
- Christian Daniel Klink
- Department of General, Visceral and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany,
| | | | | | | | | |
Collapse
|
|
22
|
Wiig JN, Giercksky KE, Tveit KM. Intraoperative radiotherapy for locally advanced or locally recurrent rectal cancer: Does it work at all? Acta Oncol 2014; 53:865-76. [PMID: 24678823 DOI: 10.3109/0284186x.2014.895037] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Intraoperative radiotherapy (IORT) has been given for primary and locally recurrent rectal cancer for 30 years. Still, its effect is not clear. MATERIAL AND METHODS PubMed and EMBASE search for papers after 1989 on surgical treatment and external beam radiotherapy (EBRT) for primary advanced and locally recurrent rectal cancer, with and without IORT. From each center the most recent paper was generally selected. Survival and local recurrence at five years was tabulated for the total groups and separate R-stages. Also, the technique for IORT, use of EBRT and chemotherapy as well as surgical approach was registered. RESULTS In primary cancer 18 papers from 14 centers were tabulated, including one randomized and five internally comparing studies, as well as seven studies without IORT. In locally recurrent cancer 18 papers from 13 centers were tabulated, including four internally comparing studies and also five without IORT. Overall survival (OS) and local recurrence rate (LRR) were higher for primary cancer compared to recurrent cancer. Patients with R0 resections had better outcome than patients with R1 or R2 resections. For primary cancer OS and LR rate of the total groups and R0 stages was not influenced by IORT. An effect on R1/R2 stages cannot be excluded. The only randomized study (primary cancer) did not show any effect of IORT. CONCLUSION IORT does not convincingly improve OS and LR rate for primary and locally recurrent rectal cancer. If there is an effect of IORT, it is small and cannot be shown outside randomized studies analyzing the separate R stages.
Collapse
Affiliation(s)
- Johan N Wiig
- Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway
| | | | | |
Collapse
|
|
23
|
Alberda WJ, Verhoef C, Nuyttens JJ, van Meerten E, Rothbarth J, de Wilt JHW, Burger JWA. Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2014; 88:1032-40. [PMID: 24661656 DOI: 10.1016/j.ijrobp.2014.01.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 01/07/2014] [Accepted: 01/10/2014] [Indexed: 01/15/2023]
Abstract
PURPOSE Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. METHODS AND MATERIALS All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. RESULTS A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) CONCLUSION: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.
Collapse
Affiliation(s)
- Wijnand J Alberda
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Joost J Nuyttens
- Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Joost Rothbarth
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Division of Surgical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - Jacobus W A Burger
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
| |
Collapse
|
|
24
|
Mirnezami R, Chang GJ, Das P, Chandrakumaran K, Tekkis P, Darzi A, Mirnezami AH. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol 2013; 22:22-35. [PMID: 23270946 PMCID: PMC4663079 DOI: 10.1016/j.suronc.2012.11.001] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Revised: 11/03/2012] [Accepted: 11/10/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND The precise contribution of IORT to the management of locally advanced and recurrent colorectal cancer (CRC) remains uncertain. We performed a systematic review and meta-analysis to assess the value of IORT in this setting. METHODS Studies published between 1965 and 2011 that reported outcomes after IORT for advanced or recurrent CRC were identified by an electronic literature search. Studies were assessed for methodological quality and design, and evaluated for technique of IORT delivery, oncological outcomes, and complications following IORT. Outcomes were analysed with fixed-effect and random-effect model meta-analyses and heterogeneity and publication bias examined. RESULTS 29 studies comprising 14 prospective and 15 retrospective studies met the inclusion criteria and were assessed, yielding a total of 3003 patients. The indication for IORT was locally advanced disease in 1792 patients and locally recurrent disease in 1211 patients. Despite heterogeneity in methodology and reporting practice, IORT is principally applied for the treatment of close or positive margins. When comparative studies were evaluated, a significant effect favouring improved local control (OR 0.22; 95% CI = 0.05-0.86; p = 0.03), disease free survival (HR 0.51; 95% CI = 0.31-0.85; p = 0.009), and overall survival (HR 0.33; 95% CI = 0.2-0.54; p = 0.001) was noted with no increase in total (OR 1.13; 95% CI = 0.77-1.65; p = 0.57), urologic (OR 1.35; 95% CI = 0.84-2.82; p = 0.47), or anastomotic complications (OR 0.94; 95% CI = 0.42-2.1; p = 0.98). Increased wound complications were noted after IORT (OR 1.86; 95% CI = 1.03-3.38; p = 0.049). CONCLUSIONS Despite methodological weaknesses in the studies evaluated, our results suggest that IORT may improve oncological outcomes in advanced and recurrent CRC.
Collapse
Affiliation(s)
- Reza Mirnezami
- Section of Biosurgery & Surgical Technology, Department of Surgery & Cancer, Imperial College London, 10th Floor QEQM Building, St Mary's Hospital, London W2 1NY, UK
| | | | | | | | | | | | | |
Collapse
|
|
25
|
Masaki T, Ohkura Y, Matsuoka H, Kobayashi T, Miyano S, Abe N, Sugiyama M, Atomi Y. Rationale of pelvic autonomic nerve preservation in rectal cancer surgery based on immunohistochemical study. Int J Clin Oncol 2010; 15:462-7. [PMID: 20514506 DOI: 10.1007/s10147-010-0091-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2010] [Accepted: 04/21/2010] [Indexed: 10/19/2022]
Abstract
PURPOSE Previous studies revealed that the incidence of cancer cell involvement along the pelvic autonomic nerves ranged from 4 to 14%. However, patients' profiles and methodologies differed among the studies. This study was conducted to clarify the incidence of cancer cell involvement in and around the pelvic autonomic nerves immunohistochemically. METHODS Immunohistochemical staining was performed on pelvic autonomic nerve specimens resected from 17 patients with p-Stage I-III lower rectal cancers. Antibodies used were pan-cytokeratin (AE1/AE3) for staining cancer cells, S-100 for autonomic nerves, and D2-40 for lymphatic vessels. Lymphatic permeation around the pelvic autonomic nerves was defined as present when AE1/AE3-positive cells were detected in D2-40-stained lymphatic vessels. The presence of metastasis to the interstitial tissue or contaminants was also recorded. RESULTS TNM staging was stage I in 1, stage II in 5, and stage III in 11 cases, respectively. No cases had lymphatic permeation or metastasis to the interstitial tissue in and around the pelvic autonomic nerves. Cancer cell contaminants were seen in four cases (23%). In three cases (18%), metastatic nodes were located at the root of the middle rectal artery, very close to the pelvic autonomic nerves. CONCLUSIONS Cancer cell involvement was not seen in and around the pelvic autonomic nerves, suggesting that complete pelvic autonomic nerve preservation may be feasible, unless nerves are invaded by the tumor. In some cases, however, metastatic nodes were seen very close to the nerves. Meticulous lymph node dissection along the pelvic autonomic nerves is mandatory.
Collapse
Affiliation(s)
- Tadahiko Masaki
- Department of Surgery, Kyorin University, 6-20-2 Shinkawa, Mitaka, 181-8611, Japan.
| | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Quality assurance of pelvic autonomic nerve-preserving surgery for advanced lower rectal cancer—preliminary results of a randomized controlled trial. Langenbecks Arch Surg 2010; 395:607-13. [DOI: 10.1007/s00423-010-0655-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2010] [Accepted: 05/18/2010] [Indexed: 12/20/2022]
|