|
1
|
Gharib E, Robichaud GA. From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies. Int J Mol Sci 2024; 25:9463. [PMID: 39273409 PMCID: PMC11395697 DOI: 10.3390/ijms25179463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/19/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma-carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.
Collapse
Affiliation(s)
- Ehsan Gharib
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
| | - Gilles A Robichaud
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
| |
Collapse
|
|
2
|
Deidda S, Spolverato G, Capelli G, Bao RQ, Bettoni L, Crimì F, Zorcolo L, Pucciarelli S, Restivo A. Limits of Clinical Restaging in Detecting Responders After Neoadjuvant Therapies for Rectal Cancer. Dis Colon Rectum 2023; 66:957-964. [PMID: 36538694 PMCID: PMC11584182 DOI: 10.1097/dcr.0000000000002450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Accurate clinical restaging is required to select patients who respond to neoadjuvant chemoradiotherapy for locally advanced rectal cancer and who may benefit from an organ preservation strategy. OBJECTIVE The purpose of this study was to review our experience with the clinical restaging of rectal cancer after neoadjuvant therapy to assess its accuracy in detecting major and pathological complete response to treatment. DESIGN This was a retrospective cohort study. SETTING This study was conducted at 2 high-volume Italian centers for Colorectal Surgery. PATIENTS Data were included from all consecutive patients who underwent neoadjuvant therapy and surgery for locally advanced rectal cancer from January 2012 to July 2020. Criteria to define clinical response were no palpable mass, a superficial ulcer <2 cm (major response), or no mucosal abnormality (complete response) at endoscopy and no metastatic nodes at MRI. MAIN OUTCOME MEASURES The main outcome measures were sensitivity, specificity, positive predictive values, and negative predictive values of clinical restaging in detecting pathological complete response (ypT0) or major pathological response (ypT0-1) after neoadjuvant therapy. RESULTS A total of 333 patients were included; 81 (24.3%) had a complete response whereas 115 (34.5%) had a pathological major response. Accuracy for clinical complete response was 80.8% and for major clinical response was 72.9%. Sensitivity was low for both clinical complete response (37.5%) in detecting ypT0 and clinical major response (59.3%) in detecting ypT0-1. Positive predictive value was 68.2% for ypT0 and 60.4% for ypT0-1. LIMITATIONS The main limitation of the study its retrospective nature. CONCLUSION Accuracy of actual clinical criteria to define pathological complete response or pathological major response is poor. Failure to achieve good sensitivity and precision is a major limiting factor in the clinical setting. Current clinical assessments need to be revised to account for indications for rectal preservation after neoadjuvant chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/C63 . LMITES DE LA REESTADIFICACIN CLNICA EN LA DETECCIN DE RESPONDEDORES DESPUS DE TERAPIAS NEOADYUVANTES PARA EL CNCER DE RECTO ANTECEDENTES:Se requiere una nueva reestadificación clínica precisa para seleccionar pacientes que respondan a la quimiorradioterapia neoadyuvante para el cáncer de recto localmente avanzado y que puedan beneficiarse de una estrategia de preservación de órganos.OBJETIVO:El propósito de este estudio fue revisar nuestra experiencia con la reestadificación clínica del cáncer de recto después de la terapia neoadyuvante para evaluar su precisión en la detección de una respuesta patológica importante y completa al tratamiento.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Este estudio se realizó en dos centros italianos de alto volumen para cirugía colorrectal.PACIENTES:Incluimos datos de todos los pacientes consecutivos que se sometieron a terapia neoadyuvante y cirugía por cáncer de recto localmente avanzado desde enero de 2012 hasta julio de 2020. Los criterios para definir la respuesta clínica fueron ausencia de masa palpable, úlcera superficial <2 cm (respuesta mayor) o ausencia de anomalías en la mucosa. (respuesta completa) en la endoscopia, y sin ganglios metastásicos en la resonancia magnética.PRINCIPALES MEDIDAS DE RESULTADO:Exploramos la sensibilidad, la especificidad, los valores predictivos positivos y negativos de la reestadificación clínica para detectar una respuesta patológica completa (ypT0) o mayor (ypT0-1) después de la terapia neoadyuvante.RESULTADOS:Se incluyeron 333 pacientes; 81 (24,3%) tuvieron una respuesta completa mientras que 115 (34,5%) tuvieron una respuesta patológica mayor. La precisión de la respuesta clínica completa y la respuesta clínica importante fue del 80,8 % y el 72,9 %, respectivamente. La sensibilidad fue baja tanto para la respuesta clínica completa (37,5 %) en la detección de ypT0 como para la respuesta clínica mayor (59,3 %) en la detección de ypT0-1. El valor predictivo positivo fue del 68,2 % para ypT0 y del 60,4 % para ypT0-1.LIMITACIONES:Nuestro estudio tiene como principal limitación su carácter retrospectivo.CONCLUSIÓNES:La precisión de los criterios clínicos reales para definir una respuesta patológica completa o mayor es pobre. El hecho de no lograr una buena sensibilidad y precisión es un factor limitante importante en el entorno clínico. La indicación para la preservación rectal después de la quimiorradioterapia neoadyuvante necesita una mejora de la evaluación clínica actual. Consulte Video Resumen en http://links.lww.com/DCR/C63 . (Traducción-Dr. Mauricio Santamaria ).
Collapse
Affiliation(s)
- Simona Deidda
- Department of Surgical Science, University of Cagliari, Cagliari, Italy
| | - Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy
| | - Giulia Capelli
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy
| | - Riccardo Quoc Bao
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy
| | - Lorenzo Bettoni
- Department of Medicine (DIMED), Institute of Radiology, University of Padova, Padua, Italy
| | - Filippo Crimì
- Department of Medicine (DIMED), Institute of Radiology, University of Padova, Padua, Italy
| | - Luigi Zorcolo
- Department of Surgical Science, University of Cagliari, Cagliari, Italy
| | - Salvatore Pucciarelli
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padua, Italy
| | - Angelo Restivo
- Department of Surgical Science, University of Cagliari, Cagliari, Italy
| |
Collapse
|
|
3
|
Fareed AM, Eldamshety O, Shahatto F, Khater A, Kotb SZ, Elzahaby IA, Khan JS. Local Excision Versus Total Mesorectal Excision After Favourable Response to Neoadjuvant Therapy in Low Rectal Cancer: a Multi-centre Experience. Indian J Surg Oncol 2023; 14:331-338. [PMID: 37324307 PMCID: PMC10267030 DOI: 10.1007/s13193-022-01674-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 10/19/2022] [Indexed: 11/09/2022] Open
Abstract
The gold standard surgical management of curable rectal cancer is proctectomy with total mesorectal excision. Adding preoperative radiotherapy improved local control. The promising results of neoadjuvant chemoradiotherapy raised the hopes for conservative, yet oncologically safe management, probably using local excision technique. This study is a prospective comparative phase III study, where 46 rectal cancer patients were recruited from patients attending Oncology Centre of Mansoura University and Queen Alexandra Hospital Portsmouth University Hospital NHS with a median follow-up 36 months. The two recruited groups were as follows: group (A), 18 patients who underwent conventional radical surgery by TME; and group (B), 28 patients who underwent trans-anal endoscopic local excision. Patients of resectable low rectal cancer (below 10 cms from anal verge) with sphincter saving procedures were included: cT1-T3N0. The median operative time for LE was 120 min versus 300 in TME (p < 0.001), and median blood loss was 20 ml versus 100 ml in LE and TME, respectively (p < 0.001). Median hospital stay was 3.5 days versus 6.5 days (p = 0.009). No statistically significant difference in median DFS (64.2 months for LE versus 63.2 months for TME, p = 0.85) and median OS (72.9 months for LE versus 76.3 months for TME, p = 0.43). No statistically significant difference in LARS scores and QoL was observed between LE and TME (p = 0.798, p = 0.799). LE seems a good alternative to radical rectal resection in carefully selected responders to neoadjuvant therapy after thorough pre-operative evaluation, planning and patient counselling.
Collapse
Affiliation(s)
| | | | - Fayz Shahatto
- Mansoura University Oncology Center, Mansoura, Egypt
| | - Ashraf Khater
- Mansoura University Oncology Center, Mansoura, Egypt
| | | | | | - Jim S. Khan
- Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| |
Collapse
|
|
4
|
Soriano C, Bahnson HT, Kaplan JA, Lin B, Moonka R, Pham HT, Kennecke HF, Simianu V. Contemporary, national patterns of surgery after preoperative therapy for stage II/III rectal adenocarcinoma. World J Gastrointest Oncol 2022; 14:1148-1161. [PMID: 35949222 PMCID: PMC9244989 DOI: 10.4251/wjgo.v14.i6.1148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 04/11/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Contemporary treatment of stage II/III rectal cancer combines chemotherapy, chemoradiation, and surgery, though the sequence of surgery with neoadjuvant treatments and benefits of minimally-invasive surgery (MIS) is debated. AIM To describe patterns of surgical approach for stage II/III rectal cancer in relation to neoadjuvant therapies. METHODS A retrospective cohort was created using the National Cancer Database. Primary outcome was rate of sphincter-sparing surgery after neoadjuvant therapy. Secondary outcomes were surgical approach (open, laparoscopic, or robotic), surgical quality (R0 resection and 12+ lymph nodes), and overall survival. RESULTS A total of 38927 patients with clinical stage II or III rectal adenocarcinoma underwent surgical resection from 2010-2016. Clinical stage II patients had neoadjuvant chemoradiation less frequently compared to stage III (75.8% vs 84.7%, P < 0.001), but had similar rates of total neoadjuvant therapy (TNT) (27.0% vs 27.2%, P = 0.697). Overall rates of total mesorectal excision without sphincter preservation were similar between clinical stage II and III (30.0% vs 30.3%) and similar if preoperative treatment was chemoradiation (31.3%) or TNT (30.2%). Over the study period, proportion of cases approached laparoscopically increased from 24.9% to 32.5% and robotically 5.6% to 30.7% (P < 0.001). This cohort showed improved survival for MIS approaches compared to open surgery (laparoscopy HR 0.85, 95%CI 0.78-0.93, and robotic HR 0.82, 95%CI 0.73-0.92). CONCLUSION Sphincter preservation rates are similar across stage II and III rectal cancer, regardless of delivery of preoperative chemotherapy, chemoradiation, or both. At a national level, there is a shift to predominantly MIS approaches for rectal cancer, regardless of whether sphincter sparing procedure is performed.
Collapse
Affiliation(s)
- Celine Soriano
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Henry T Bahnson
- Benaroya Research Institute, Seattle, WA 98101, United States
| | - Jennifer A Kaplan
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Bruce Lin
- Department of Hematology Oncology, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Ravi Moonka
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Huong T Pham
- Department of Radiation Oncology, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Hagen F Kennecke
- Department of Medical Oncology, Providence Cancer Instititute, Portland, OR 97213, United States
| | - Vlad Simianu
- Section of Colon and Rectal Surgery, Department of Surgery, Virginia Mason Medical Center, Seattle, WA 98101, United States
| |
Collapse
|
|
5
|
Socha J, Kairevice L, Kępka L, Michalski W, Spałek M, Paciorek K, Bujko K. Should Short-Course Neoadjuvant Radiation Therapy Be Applied for Low-Lying Rectal Cancer? A Systematic Review and Meta-Analysis of the Randomized Trials. Int J Radiat Oncol Biol Phys 2020; 108:1257-1264. [PMID: 32634546 DOI: 10.1016/j.ijrobp.2020.06.077] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/16/2020] [Accepted: 06/28/2020] [Indexed: 01/17/2023]
Abstract
PURPOSE National Comprehensive Cancer Network guidelines recommend either long-course chemoradiation (LC) or short-course radiation (SC, 5 × 5 Gy) for rectal cancer before total mesorectal excision. However, they do not recommend SC for low-lying tumors. As early toxicity of SC is lower than that of LC, and postoperative complications as well as late toxicity are similar, the probable reason is a notion that for low-lying tumors LC may be more effective than SC in assuring local control. METHODS AND MATERIALS A systematic review and meta-analysis of the randomized trials comparing SC with LC was performed to test the hypothesis that for low-lying tumors, LC is superior to SC in reducing the risk of local failure. RESULTS The systematic search identified 4 trials including, in total, 421 patients with tumors <5 cm from the anal verge; 221 were randomized to SC and 200 to LC. The meta-analysis showed that the difference in local failure rate between SC and LC was insignificant; the pooled odds ratio was 0.87, 95% confidence interval 0.53 to 1.44, P = .59. Heterogeneity between trials was insignificant; I2 = 0.0%, P = .47. CONCLUSIONS Our meta-analysis does not support the notion that LC given before total mesorectal excision is superior to SC in reducing the risk of local failure in low-lying tumors.
Collapse
Affiliation(s)
- Joanna Socha
- Department of Radiotherapy, Military Institute of Medicine, Warsaw, Poland; Department of Radiotherapy, Regional Oncology Centre, Czestochowa, Poland.
| | - Laura Kairevice
- Department of Oncology and Hematology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Lucyna Kępka
- Department of Radiotherapy, Military Institute of Medicine, Warsaw, Poland
| | - Wojciech Michalski
- Bioinformatics and Biostatistics Unit, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Mateusz Spałek
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Karol Paciorek
- Department of Radiotherapy I, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Krzysztof Bujko
- Department of Radiotherapy I, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| |
Collapse
|
|
6
|
Collard M, Lefevre JH. Ultimate Functional Preservation With Intersphincteric Resection for Rectal Cancer. Front Oncol 2020; 10:297. [PMID: 32195192 PMCID: PMC7066078 DOI: 10.3389/fonc.2020.00297] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 02/20/2020] [Indexed: 12/11/2022] Open
Abstract
The proximity of the very low rectum rectal cancer to the anal sphincter raises a specific problem: how and until when can we preserve the anal continence without compromising the oncological result of the tumor resection? In this situation, intersphincteric resection (ISR) offers an excellent alternative to abdominoperineal resection (APR), but the selection of patients for this option must be extremely precise. This complex choice justifies the simultaneous consideration of an oncological approach with a functional approach in order to provide a full benefit to the patient. When a circumferential resection margin of at least 1 mm can be performed with a distal resection margin of at least 1 cm with or without preoperative radiotherapy, ISR ensures a safety choice. The oncological results of ISR reported in the literature when performed properly found a 5-year disease-free survival of 80.2% with a local recurrence rate of only 5.8%. In parallel to this oncological evaluation, the expected post-operative functional outcome and the resulting quality of life must be properly assessed pre-operatively, since partial or total resection of the internal sphincter impacts significantly on the functional outcome. Based on data from the literature, this work reports the essential anatomical considerations and then the oncological and functional elements indispensables when an anal continence preservation is evoked for a tumor of the very low rectum. Finally, the precise selection criteria and the major surgical principles are outlined in order to guarantee the safety of this modern choice for the patient.
Collapse
Affiliation(s)
- Maxime Collard
- Sorbonne Université, Department of Digestive Surgery, AP-HP, Hôpital Saint Antoine, Paris, France
| | - Jérémie H Lefevre
- Sorbonne Université, Department of Digestive Surgery, AP-HP, Hôpital Saint Antoine, Paris, France
| |
Collapse
|
|
7
|
Yang Y, Liu Q, Jia B, Du X, Dai G, Liu H, Chen J, Zeng M, Wen K, Zhu Y, Wang Y, Feng L. Preoperative Volumetric Modulated Arc Therapy With Simultaneous Integrated Boost for Locally Advanced Distal Rectal Cancer. Technol Cancer Res Treat 2019; 18:1533033818824367. [PMID: 30803368 PMCID: PMC6373990 DOI: 10.1177/1533033818824367] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The aim of this study was to evaluate the safety and clinical efficacy of a combined preoperative regimen consisting of volumetric modulated arc therapy–simultaneous integrated boost and capecitabine chemotherapy for distal rectal cancer. A total of 26 patients with locally advanced distal rectal cancer were enrolled from March 2015 to May 2016. The radiation dose fractionation was 58.75 Gy/25 fractions (2.35 Gy/fraction) for rectal tumor and pelvic lymph node metastasis and 50 Gy/25 fractions for pelvic lymph node stations, accompanied with simultaneous capecitabine chemotherapy. Completion of the simultaneous chemotherapy was ensued by 1 week of rest and then another cycle of induction chemotherapy with capecitabine. A radical rectal cancer surgery was performed 6 to 8 weeks after the simultaneous chemoradiotherapy. The primary end points were the complete pathological response rate and the postoperative sphincter preservation rate. All 26 patients completed the neoadjuvant chemoradiotherapy, among which 25 received surgical treatment. The postoperative complete pathological response rate was as high as 32% (8/25), while the sphincter preservation rate was 60% (15/25), the overall tumor/node (T/N) downstaging rate was 92% (23/25), and the R0 resection rate was 100%. During the chemoradiation, the most common adverse events were grade 1 and 2; grade 3 radiodermatitis occurred in 2 cases but no occurrence of acute adverse events occurred that were grade 4 and above. After the surgery, there was one case of ureteral injury and one case of intestinal obstruction, but no perioperative deaths occurred. In conclusion, the chemoradiation regimen of preoperative volumetric modulated arc therapy-simultaneous integrated boost (VMAT-SIB58.75Gy) and a single cycle of induction chemotherapy with capecitabine for patients with distal rectal cancer is safe and feasible with a satisfactory complete pathological response rate, sphincter preservation rate, and R0 resection rate.
Collapse
Affiliation(s)
- Yongqiang Yang
- 1 Department of Radiotherapy & Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Qiteng Liu
- 2 Department of Radiation Oncology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Baoqing Jia
- 3 Department of Surgical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Xiaohui Du
- 4 Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Guanghai Dai
- 5 Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Hongyi Liu
- 3 Department of Surgical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Jing Chen
- 6 Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China
| | - Mingyue Zeng
- 6 Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China
| | - Ke Wen
- 7 Department of Radiation Oncology, Chinese PLA 302 Hospital, Beijing, China
| | - Yaqun Zhu
- 1 Department of Radiotherapy & Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yunlai Wang
- 6 Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China
| | - Linchun Feng
- 6 Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
|
8
|
Ma B, Gao P, Song Y, Huang X, Wang H, Xu Q, Zhao S, Wang Z. Short-Course Radiotherapy in Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-analysis. Clin Colorectal Cancer 2018; 17:320-330.e5. [DOI: 10.1016/j.clcc.2018.07.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 07/23/2018] [Accepted: 07/28/2018] [Indexed: 02/07/2023]
|
|
9
|
Cunningham HB, Weis JJ, Taveras LR. Current Trends in the Rate of Rectal Cancer Restorative Operations in the Era of Neoadjuvant Chemoradiation. CURRENT COLORECTAL CANCER REPORTS 2018. [DOI: 10.1007/s11888-018-0400-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
|
|
10
|
Kim JH. Controversial issues in radiotherapy for rectal cancer: a systematic review. Radiat Oncol J 2017; 35:295-305. [PMID: 29325395 PMCID: PMC5769877 DOI: 10.3857/roj.2017.00395] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 09/28/2017] [Accepted: 10/02/2017] [Indexed: 12/17/2022] Open
Abstract
The role of radiotherapy (RT) as an adjuvant to surgical options in the treatment of locally advanced rectal cancer has been established as it reduces local recurrence when combined with surgical resection and enhances survival when used in multidisciplinary treatment. However, many issues need to be addressed; some of these can render RT unnecessary, whereas others can reveal a new role of RT in rectal cancer. This review will discuss not only the basic role of RT but also the associated but controversial issues in detail in an attempt to find answers and determine future directions for the next decade.
Collapse
Affiliation(s)
- Jong Hoon Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
11
|
Denost Q, Rullier E. Intersphincteric Resection Pushing the Envelope for Sphincter Preservation. Clin Colon Rectal Surg 2017; 30:368-376. [PMID: 29184472 DOI: 10.1055/s-0037-1606114] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
During the last 15 years, a significant evolution has emerged in the surgical treatment of rectal cancer and restoration of bowel continuity has been one of the main goals. For many years the treatment of distal rectal cancer would necessarily require an abdominoperineal resection and end colostomy. The surgical procedure of intersphincteric resection has been proposed to offer sphincter preservation in patients with low rectal cancer and has been legitimized if executed according to adequate oncologic criteria. This article will discuss the best indications, technical aspects, functional, and oncological outcomes of intersphicteric resection in the management of rectal cancer.
Collapse
Affiliation(s)
- Quentin Denost
- Colorectal Unit, Department of Surgery, Centre Magellan, Haut Lévèque University Hospital, Bordeaux/Pessac, France
| | - Eric Rullier
- Colorectal Unit, Department of Surgery, Centre Magellan, Haut Lévèque University Hospital, Bordeaux/Pessac, France
| |
Collapse
|
|
12
|
Ma B, Xu Q, Song Y, Gao P, Wang Z. Current issues of preoperative radio(chemo)therapy and its future evolution in locally advanced rectal cancer. Future Oncol 2017; 13:2489-2501. [PMID: 29124955 DOI: 10.2217/fon-2017-0310] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Neoadjuvant therapies are effective for local control and tumor downstaging. Up to date, preoperative long-course chemoradiotherapy and short-course radiotherapy are the two primary guideline-recommended neoadjuvant therapies for locally advanced rectal cancer patients. However, clinicians throughout the world are trying their best to further optimize the regimens and concepts of neoadjuvants. Hence, there is an urgent need to summarize evidence regarding indications of neaoadjuvant therapies and relative merits of current standard regimens. In addition, we also reviewed the optimized regimens mainly based on short-course radiotherapy with delayed surgery, consolidation chemotherapy, induction chemotherapy, chemotherapy alone without radiation and concepts in terms of organ preservation and personalized treatments to further explore the future evolution of neoadjuvant therapies in rectal cancer.
Collapse
Affiliation(s)
- Bin Ma
- Department of Surgical Oncology & General Surgery, the First Hospital of China Medical University, Shenyang 110001, PR China
| | - Qingzhou Xu
- Department of Surgical Oncology & General Surgery, the First Hospital of China Medical University, Shenyang 110001, PR China
| | - Yongxi Song
- Department of Surgical Oncology & General Surgery, the First Hospital of China Medical University, Shenyang 110001, PR China
| | - Peng Gao
- Department of Surgical Oncology & General Surgery, the First Hospital of China Medical University, Shenyang 110001, PR China
| | - Zhenning Wang
- Department of Surgical Oncology & General Surgery, the First Hospital of China Medical University, Shenyang 110001, PR China
| |
Collapse
|
|
13
|
Idasiak A, Galwas-Kliber K, Behrendt K, Wziętek I, Kryj M, Stobiecka E, Chmielik E, Suwiński R. Pre-operative hyperfractionated concurrent radiochemotherapy for locally advanced rectal cancers: a phase II clinical study. Br J Radiol 2017; 90:20160731. [PMID: 28466686 DOI: 10.1259/bjr.20160731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE The study was prospectively designed as a single-arm, single-institution prospective trial of pre-operative concomitant hyperfractionated radiotherapy (HART) with co-administration of chemotherapy based on 5-fluorouracil (5FU) in patients with T2/N+ or T3/any N resectable mid-low primary rectal cancer. The aim of the study was to assess the safety and efficacy of accelerated HART with concurrent 5FU-based chemotherapy in patients with locally advanced rectal cancer. METHODS Patients with resectable locally advanced (≥T3 or N+) rectal cancer were eligible. The patients received total dose 42 Gy in 28 fractions of 1.5 Gy, two times daily, with at least 8 h of interval, with concurrent chemotherapy: 325 mg m-2 of 5FU (bolus) on Days 1-3 and Days 16-18 (except for cN0 patients for whom only one cycle on Days 1-3 was prescribed). The primary end point included tolerance, post-operative complication rate and pathological response rate. The secondary end points included locoregional relapse-free survival, metastasis-free survival and overall survival. RESULTS Out of 53 enrolled patients; 2 did not undergo surgery. Of the 51 patients evaluable for pathological response, there were 8 (15.6%), 20 (39.3%), 18 (35.3%) and 5 (9.8%) patients with tumour regression grade 0, 1, 2 and 3, respectively. Downstaging of the primary tumour and lymph nodes was observed in 22 (43%) and 25 (49%) patients, respectively. The primary tumour ypCR (ypT0) rate was 15% (8/51). The nodal ypCR rate for cN+ patients was 60% (21/35). The total ypCR (ypT0N0M0) rate was 11% (6/51). Toxicity included: Grade 3 diarrhoea (4/51, 7.8%), Grade 2 diarrhoea (22/51, 43.1%), Grade 2 leukopenia (7/51, 13.7%), Grade 2 neutropenia (6/51, 11.7%) and Grade 1 thrombocytopenia (3/51, 5.9%). No Grade 4 toxicity was reported. Nine patients (18%) presented with post-operative complications (during the 3 months after surgery). There were 6 locoregional relapses (11.8%) and distant metastasis occurred in 11 patients (21.6%). The 2-year cumulative locoregional relapse-free survival, metastasis-free survival and overall survival was 87%, 79% and 89%, respectively. CONCLUSION The proposed pre-operative HART with co-administration of 5FU had acceptable toxicity profile and provided satisfactory rate of ypCR. This created rationale to initiate a Phase III randomized study that was registered under ClinicalTrials.gov Identifier: NCT01814969. Advances in knowledge: The results of this research show that responders to pre-operative radiochemotherapy have favourable outcome. Tumour regression grade as prognostic clinical feature holds the promise of better classifying patients at high risk of local and systemic recurrence and this issue may be an interesting objective for future research.
Collapse
Affiliation(s)
- Adam Idasiak
- 1 Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Katarzyna Galwas-Kliber
- 1 Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Katarzyna Behrendt
- 1 Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Iwona Wziętek
- 2 Radiotherapy Department, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Mariusz Kryj
- 3 Department of Surgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Ewa Stobiecka
- 4 Department of Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Ewa Chmielik
- 4 Department of Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| | - Rafał Suwiński
- 1 Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
| |
Collapse
|
|
14
|
Haddad P, Miraie M, Farhan F, Fazeli MS, Alikhassi A, Maddah-Safaei A, Aghili M, Kalaghchi B, Babaei M. Addition of oxaliplatin to neoadjuvant radiochemotherapy in MRI-defined T3, T4 or N+ rectal cancer: a randomized clinical trial. Asia Pac J Clin Oncol 2017; 13:416-422. [DOI: 10.1111/ajco.12675] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 01/15/2017] [Indexed: 12/01/2022]
Affiliation(s)
- Peiman Haddad
- Radiation Oncology Research Centre; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Monir Miraie
- Cancer Research Centre & Radiation Oncology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Farshid Farhan
- Cancer Research Centre & Radiation Oncology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Mohammad-Sadegh Fazeli
- Colorectal Surgery Department; Imam-Khomeini Hospital; Tehran University of Medical Sciences; Tehran Iran
| | - Afsaneh Alikhassi
- Radiology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Afsaneh Maddah-Safaei
- Radiation Oncology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Mahdi Aghili
- Radiation Oncology Research Centre & Radiation Oncology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Bita Kalaghchi
- Radiation Oncology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Mohammad Babaei
- Radiation Oncology Department; Cancer Institute; Tehran University of Medical Sciences; Tehran Iran
| |
Collapse
|
|
15
|
Interpretative Guidelines and Possible Indications for Indocyanine Green Fluorescence Imaging in Robot-Assisted Sphincter-Saving Operations. Dis Colon Rectum 2017; 60:376-384. [PMID: 28267004 DOI: 10.1097/dcr.0000000000000782] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Since the introduction of indocyanine green angiography more than 25 years ago, few studies have presented interpretative guidelines for indocyanine green fluorescent imaging. OBJECTIVE We aimed to provide interpretative guidelines for indocyanine green fluorescent imaging through quantitative analysis and to suggest possible indications for indocyanine green fluorescent imaging during robot-assisted sphincter-saving operations. DESIGN This is a retrospective observational study. SETTINGS This study was conducted at a single center. PATIENTS A cohort of 657 patients with rectal cancer who consecutively underwent curative robot-assisted sphincter-saving operations was enrolled between 2010 and 2016, including 310 patients with indocyanine green imaging (indocyanine green fluorescent imaging+ group) and 347 patients without indocyanine green imaging (indocyanine green fluorescent imaging- group). MAIN OUTCOME MEASURES We tried to quantitatively define the indocyanine green fluorescent imaging findings based on perfusion (mesocolic and colic) time and perfusion intensity (5 grades) to provide probable indications. RESULTS The anastomotic leakage rate was significantly lower in the indocyanine green fluorescent imaging+ group than in the indocyanine green fluorescent imaging- group (0.6% vs 5.2%) (OR, 0.123; 95% CI, 0.028-0.544; p = 0.006). Anastomotic stricture was closely correlated with anastomotic leakage (p = 0.002) and a short descending mesocolon (p = 0.003). Delayed perfusion (>60 s) and low perfusion intensity (1-2) were more frequently detected in patients with anastomotic stricture and marginal artery defects than in those without these factors (p ≤ 0.001). In addition, perfusion times greater than the mean were more frequently observed in patients aged >58 years, whereas low perfusion intensity was seen more in patients with short descending mesocolon and high ASA classes (≥3). LIMITATIONS The 300 patients in the indocyanine green fluorescent imaging- group underwent operations 3 years before indocyanine green fluorescent imaging. CONCLUSIONS Quantitative analysis of indocyanine green fluorescent imaging may help prevent anastomotic complications during robot-assisted sphincter-saving operations, and may be of particular value in high-class ASA patients, older patients, and patients with a short descending mesocolon.
Collapse
|
|
16
|
Zhen L, Wang Y, Zhang Z, Wu T, Liu R, Li T, Zhao L, Deng H, Qi X, Li G. Effectiveness between early and late temporary ileostomy closure in patients with rectal cancer: A prospective study. Curr Probl Cancer 2017; 41:231-240. [PMID: 28434582 DOI: 10.1016/j.currproblcancer.2017.02.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 02/27/2017] [Indexed: 11/29/2022]
Abstract
A temporary stoma is often used in rectal cancer surgery to protect a distal anastomosis, which remains a major concern after rectal cancer surgery, particularly after low anterior resection. The temporary stoma is scheduled for closure. However, the optimal time of closure of the protecting stoma remains unclear because of sparse studies and data. We aimed to detect the efficacy between early and late temporary ileostomy closure in patients with rectal cancer during or after neoadjuvant chemoradiotherapy. We conducted a prospective, 2-group design between early and late ileostomy closure group in patients after rectal cancer surgery with temporary stoma. Participants were recruited in a teaching hospital in Guangzhou, China. A total of 161 patients confirmed diagnosis of rectal cancer underwent curative surgery and temporary ileostomy. Participants with temporary ileostomy received closure surgery after 1 (early) or 6 (late) months were assessed by clinical parameters and quality of life. Patients in late closure group received more adjuvant chemotherapy cycles but with comparable incidence of stoma closure-related complications and length of hospital stay compared to early closure group. Participants in late closure group with standardized postoperative chemotherapy might have a better prognosis compared with those in early closure group. An increased emphasis should be given to choose the optimal closure time of patients with rectal cancer having temporary ileostomy. Colorectal nurses could provide support to physician for observation of prognosis of different closure time.
Collapse
Affiliation(s)
- Li Zhen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yanan Wang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ze Zhang
- Department of Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tongwei Wu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ruoyan Liu
- Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tingting Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liying Zhao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Haijun Deng
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaolong Qi
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| |
Collapse
|
|
17
|
Park IJ, Yu CS, Lim SB, Lee JL, Kim CW, Yoon YS, Park SH, Kim JC. Is Preoperative Chemoradiotherapy Beneficial for Sphincter Preservation in Low-Lying Rectal Cancer Patients? Medicine (Baltimore) 2016; 95:e3463. [PMID: 27149445 PMCID: PMC4863762 DOI: 10.1097/md.0000000000003463] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The present study explored the benefit of preoperative chemoradiotherapy (PCRT) for sphincter preservation in locally advanced low-lying rectal cancer patients who underwent stapled anastomosis, especially in those with deep and narrow pelvises determined by magnetic resonance imaging.Patients with locally advanced low-lying rectal cancer (≤5 cm from the anal verge) who underwent stapled anastomosis were included. Patients were categorized into two groups (PCRT+ vs. PCRT-) according to PCRT application. Patients in the PCRT+ group were matched to those in the PCRT- group according to potential confounding factors (age, gender, clinical stage, and body mass index) for sphincter preservation. Sphincter preservation, permanent stoma, and anastomosis-related complications were compared between the groups. Pelvic magnetic resonance imaging was used to measure 12 dimensions representing pelvic cavity depth and width with which deep and narrow pelvis was defined. The impact of PCRT on sphincter preservation and permanent stoma in pelvic dimensions defined as deep and narrow pelvis was evaluated, and factors associated with sphincter preservation and permanent stoma were analyzed.One hundred sixty-six patients were one-to-one matched between the PCRT+ and PCRT- groups. Overall, sphincter-saving surgery was performed in 66.3% and the rates were not different between the 2 groups. Anastomotic complications and permanent stoma occurred nonsignificantly more frequently in the PCRT+ group. PCRT was not associated with higher rate of sphincter preservation in all pelvic dimensions defined as deep and narrow pelvis, while PCRT was related to higher rate of permanent stoma in shorter transverse diameter and interspinous distance. On logistic regression analysis, PCRT was not shown to influence both sphincter preservation and permanent stoma, while longer transverse diameter and interspinous distance were associated with lower rate of permanent stoma.PCRT had no beneficial effect on sphincter preservation in patients with locally advanced low-lying rectal cancer who had undergone stapled anastomosis. In patients with deep and narrow pelvis, PCRT had no impact on sphincter preservation but was associated with higher rate of permanent stoma.
Collapse
Affiliation(s)
- In Ja Park
- From the Department of Colon and Rectal Surgery (IJP, CSY, S-BL, JLL, CWK, YSY, JCK); and Department of Radiology (SHP), University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Shoji H, Motegi M, Osawa K, Okonogi N, Okazaki A, Andou Y, Asao T, Kuwano H, Takahashi T, Ogoshi K. Radiofrequency thermal treatment with chemoradiotherapy for advanced rectal cancer. Oncol Rep 2016; 35:2569-75. [PMID: 26985914 PMCID: PMC4811390 DOI: 10.3892/or.2016.4659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/10/2015] [Indexed: 01/06/2023] Open
Abstract
We previously reported that patients with a clinical complete response (CR) following radiofrequency thermal treatment exhibit significantly increased body temperature compared with other groups, whereas patients with a clinical partial response or stable disease depended on the absence or presence of output limiting symptoms. The aim of this study was to evaluate the correlation among treatment response, Hidaka radiofrequency (RF) output classification (HROC: termed by us) and changes in body temperature. From December 2011 to January 2014, 51 consecutive rectal cancer cases were included in this study. All patients underwent 5 RF thermal treatments with concurrent chemoradiation. Patients were classified into three groups based on HROC: with ≤9, 10–16, and ≥17 points, calculated as the sum total points of five treatments. Thirty-three patients received surgery 8 weeks after treatment, and among them, 32 resected specimens were evaluated for histological response. Eighteen patients did not undergo surgery, five because of progressive disease (PD) and 13 refused because of permanent colostomy. We demonstrated that good local control (ypCR + CR + CRPD) was observed in 32.7% of cases in this study. Pathological complete response (ypCR) was observed in 15.7% of the total 51 patients and in 24.2% of the 33 patients who underwent surgery. All ypCR cases had ≥10 points in the HROC, but there were no patients with ypCR among those with ≤9 points in the HROC. Standardization of RF thermal treatment was performed safely, and two types of patients were identified: those without or with increased temperatures, who consequently showed no or some benefit, respectively, for similar RF output thermal treatment. We propose that the HROC is beneficial for evaluating the efficacy of RF thermal treatment with chemoradiation for rectal cancer, and the thermoregulation control mechanism in individual patients may be pivotal in predicting the response to RF thermal treatment.
Collapse
Affiliation(s)
- Hisanori Shoji
- Division of Surgery, Hidaka Hospital, Gunma 370-0001, Japan
| | | | - Kiyotaka Osawa
- Division of Surgery, Hidaka Hospital, Gunma 370-0001, Japan
| | | | - Atsushi Okazaki
- Division of Radiology, Hidaka Hospital, Gunma 370-0001, Japan
| | | | - Takayuki Asao
- Department of Oncology Clinical Development, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
| | - Takeo Takahashi
- Department of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Saitama 350‑8550, Japan
| | - Kyoji Ogoshi
- Division of Cancer Diagnosis and Cancer Treatment, Hidaka Hospital, Gunma 370-0001, Japan
| |
Collapse
|
|
19
|
Celerier B, Denost Q, Van Geluwe B, Pontallier A, Rullier E. The risk of definitive stoma formation at 10 years after low and ultralow anterior resection for rectal cancer. Colorectal Dis 2016; 18:59-66. [PMID: 26391723 DOI: 10.1111/codi.13124] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Accepted: 05/15/2015] [Indexed: 12/11/2022]
Abstract
AIM The long-term risk of definitive stoma after sphincter-saving resection (SSR) for rectal cancer is underestimated and has never been reported for ultralow conservative surgery. We report the 10-year risk of definitive stoma after SSR for low rectal cancer. METHOD From 1994 to 2008, patients with low rectal cancer who were suitable for SSR were analysed retrospectively. Patients were divided into the following four groups: low colorectal anastomosis (LCRA); coloanal anastomosis (CAA); partial intersphincteric resection (pISR); and total intersphincteric resection (tISR). The end-point was the risk of a definitive stoma according to the type of anastomosis. RESULTS During the study period, 297 patients had SSR for low rectal cancer. The incidence of definitive stoma increased from 11% at 1 year to 22% at 10 years. The reasons were no closure of the loop ileostomy (4.7%), anastomotic morbidity (6.5%), anal incontinence (8%) and local recurrence (5.2%). The risk of definitive stoma was not influenced by type of surgery: 26% vs 18% vs 18% vs 19% (P = 0.578) for LCRA, CAA, pISR and tISR, respectively. Independent risk factors for definitive stoma were age > 65 years and surgical morbidity. CONCLUSION The risk of a definitive stoma after SSR increased two-fold between 1 and 10 years after surgery, from 11% to 22%. Ultralow conservative surgery (pISR and tISR) did not increase the risk of definitive stoma compared with conventional CAA or LCRA.
Collapse
Affiliation(s)
- B Celerier
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, France.,Université Bordeaux Segalen, Bordeaux, France
| | - Q Denost
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, France.,Université Bordeaux Segalen, Bordeaux, France
| | - B Van Geluwe
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, France.,Université Bordeaux Segalen, Bordeaux, France
| | - A Pontallier
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, France.,Université Bordeaux Segalen, Bordeaux, France
| | - E Rullier
- Department of Digestive Surgery, CHU Bordeaux, Saint André Hospital, Bordeaux, France.,Université Bordeaux Segalen, Bordeaux, France
| |
Collapse
|
|
20
|
Gérard JP, Doyen J, Barbet N. New Neoadjuvant Treatment Strategies for Non-Metastatic Rectal Cancer (M0). CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0287-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
21
|
Cotte E, Passot G, Decullier E, Maurice C, Glehen O, François Y, Lorchel F, Chapet O, Gerard JP. Pathologic Response, When Increased by Longer Interval, Is a Marker but Not the Cause of Good Prognosis in Rectal Cancer: 17-year Follow-up of the Lyon R90-01 Randomized Trial. Int J Radiat Oncol Biol Phys 2015; 94:544-53. [PMID: 26723110 DOI: 10.1016/j.ijrobp.2015.10.061] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 10/27/2015] [Accepted: 10/29/2015] [Indexed: 12/16/2022]
Abstract
PURPOSE The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years. METHODS AND MATERIALS Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery. RESULTS LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SI group (26% vs 10.3%, P=.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P=.0293 and pN: P=.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival (P=.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P=.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients). CONCLUSIONS The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence treatment decisions in adults.
Collapse
Affiliation(s)
- Eddy Cotte
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France; Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France.
| | - Guillaume Passot
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France; Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | | | | | - Olivier Glehen
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France; Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | - Yves François
- Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France; Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins, France
| | - Fabrice Lorchel
- Department of Radiotherapy, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Olivier Chapet
- Department of Radiotherapy, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Jean-Pierre Gerard
- Department of Radiotherapy, Centre Antoine-Lacassagne, University Nice-Sophia, Nice, France
| |
Collapse
|
|
22
|
Surgeon perspectives on the use and effects of neoadjuvant chemoradiation in the treatment of rectal cancer: a comprehensive review of the literature. Langenbecks Arch Surg 2015; 400:661-73. [PMID: 26250144 DOI: 10.1007/s00423-015-1328-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 07/27/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Despite screening initiatives, rectal cancer remains one of the most prevalent malignancies diagnosed in patients worldwide with a high mortality. The introduction of neoadjuvant therapy has resulted in a paradigm shift in the treatment and outcomes of rectal cancer. Surgeons play an intricate role in the pre-operative, operative, and post-operative management of these patients. PURPOSE The purpose of this comprehensive literature review was to summarize the evolution of the use chemotherapy and radiation and the process of differentiation into specific neoadjuvant chemoradiation protocols in the treatment of locally advanced rectal cancer. This will provide a concise summary for practicing surgeons of the current evidence for neoadjuvant chemoradiation as well as the various implications of therapy on operative outcomes. CONCLUSION The initial benefit of adjuvant therapy in the treatment of rectal cancer patients became evident with prospective studies demonstrating improvements in various oncologic survival outcomes. Due to the improved compliance and reduced toxicity, as well as the potential for tumor down-staging and sphincter preservation, neoadjuvant approaches became the preferred method of administering chemotherapy and radiation. Furthermore, a subgroup of patients has been shown to present with complete clinical response to neoadjuvant therapy. This has resulted in the development of the non-operative "watch and wait" approach, which has initiated discussions on changing the interval from the completion of neoadjuvant therapy to surgical resection. The continued development of the multidisciplinary approach will only further improve our ability to provide patients with the best possible oncologic outcomes.
Collapse
|
|
23
|
Quality of Life After Sphincter-Preserving Rectal Cancer Resection. Clin Colorectal Cancer 2015; 14:e33-40. [PMID: 26164498 DOI: 10.1016/j.clcc.2015.05.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 05/29/2015] [Accepted: 05/29/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND With an increasing number of cancer survivors quality of life (QoL) becomes more and more important in the treatment of rectal cancer (RC). QoL after sphincter-preserving anterior resection (AR), however, was found nonsuperior to abdominoperineal resection. The aim of our study was to evaluate QoL after AR compared with colon cancer patients after right hemicolectomy (CC) and healthy lay persons without history of cancer (HL) in long-term follow-up. PATIENTS AND METHODS Consecutive alive RC patients (n = 293) who received an AR between 1998 and 2008 were included. CC patients (n = 201) and HL of the same age were used as a surgical and a nonsurgical control group, respectively. QoL was assessed using European Organization of Research and Treatment of Cancer questionnaires QLQ-C 30 and -CR 38. RESULTS Questionnaires from 116 RC patients, 105 CC patients, and 103 HL were evaluable with a median time after surgery of 5 years. The global health status did not differ. Social functioning, future perspectives, and financial difficulties tended to poorer scores in the cancer groups. Physical functioning was better in RC and CC patients compared with HL. Defecation problems and diarrhea were more frequent in RC patients (P < .05). An additional open question revealed a median stool frequency of 3, 2, and 1 per day for RC, CC, and HL, respectively. Defecation problems were more frequent in RC patients who received radiation therapy (P < .05). CONCLUSION Diarrhea and defecation problems impaired QoL after AR for RC, which was worsened after radiation therapy. To improve QoL of RC patients in the future, physicians have to focus on minimization of gastrointestinal side effects while optimizing surgical reconstruction.
Collapse
|
|
24
|
Shoji H, Motegi M, Osawa K, Okonogi N, Okazaki A, Andou Y, Asao T, Kuwano H, Takahashi T, Ogoshi K. A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study. Cancer Med 2015; 4:834-43. [PMID: 25664976 PMCID: PMC4472206 DOI: 10.1002/cam4.431] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 01/12/2015] [Accepted: 01/13/2015] [Indexed: 01/25/2023] Open
Abstract
The safety of weekly regional hyperthermia performed with 8 MHz radiofrequency (RF) capacitive heating equipment has been established in rectal cancer. We aimed to standardize hyperthermia treatment for scientific evaluation and for assessing local tumor response to RF hyperthermia in rectal cancer. Forty-nine patients diagnosed with rectal adenocarcinoma were included in the study. All patients received chemoradiation with intensity-modulated radiation therapy 5 days/week (dose, 50 Gy/25 times) concomitant with 5 days/week for five times of capecitabine (1700 mg/m(2) per day) and once a week for five times of 50 min irradiations by an 8 MHz RF capacitive heating device. Thirty-three patients underwent surgery 8 weeks after treatment. Three patients did not undergo surgery because of progressive disease (PD) and 13 refused. Eight (16.3%) patients had a pathological complete response (ypCR) after surgery. Among patients without surgery, 3 (6.1%) had clinical complete response (CR) and 3 (6.1%) had local CR but distant PD (CRPD). Ninety percent of ypCR + CR patients were shown in 6.21 W min(-1) m(-2) /treatment or higher group of average total accumulated irradiation output with 429°C min(-1) m(-2) or higher group of total accumulated thermal output. However, a patient with CRPD was in the higher total accumulated thermal output group. We propose a new quantitative parameter for the hyperthermia and demonstrated that patients can benefit from mild irradiation with mild temperature. Using these parameters, the exact output, optimal thermal treatment, and contraindications or indications of this modality could be determined in a multi-institutional, future study.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Takayuki Asao
- Department of Oncology Clinical Development, Graduate School of Medicine, Gunma UniversityGunma, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma UniversityGunma, Japan
| | - Takeo Takahashi
- Department of Radiation Oncology, Saitama Medical Center, Saitama Medical UniversitySaitama, Japan
| | - Kyoji Ogoshi
- Division of Cancer Diagnosis and Cancer Treatment, Hidaka HospitalGunma, Japan
| |
Collapse
|
|
25
|
Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial. Radiother Oncol 2015; 115:246-52. [PMID: 25921382 DOI: 10.1016/j.radonc.2015.04.003] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 04/09/2015] [Accepted: 04/09/2015] [Indexed: 01/22/2023]
Abstract
BACKGROUND During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. MATERIAL AND METHODS Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. RESULTS The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p=0.025); tumors <4cm in diameter (14%; p=0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p=0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p<0.001); ypNO (92%); R0 circumferential margin (100%). CONCLUSION These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers.
Collapse
|
|
26
|
Habr-Gama A, Fernandez LM, Perez RO. What more do we want from neoadjuvant treatment strategies in rectal cancer? COLORECTAL CANCER 2015. [DOI: 10.2217/crc.15.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Angelita Habr-Gama
- Angelita & Joaquim Gama Institute, São Paulo, Brazil
- School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Laura M Fernandez
- Angelita & Joaquim Gama Institute, São Paulo, Brazil
- Colorectal Surgery Division, Hospital Britanico, Buenos Aires, Argentina
| | - Rodrigo O Perez
- Angelita & Joaquim Gama Institute, São Paulo, Brazil
- Colorectal Surgery Division, School of Medicine, University of São Paulo, São Paulo, Brazil
- Division of Molecular Genetics, Ludwig Institute for Cancer Research, São Paulo, Brazil
| |
Collapse
|
|
27
|
Changing Operative Strategy from Abdominoperineal Resection to Sphincter Preservation in T3 Low Rectal Cancer after Downstaging by Neoadjuvant Chemoradiation: A Preliminary Report. World J Surg 2015; 39:1248-56. [DOI: 10.1007/s00268-014-2930-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
|
|
28
|
Abstract
BACKGROUND Radiochemotherapy without surgical resection has become the treatment of choice for anal squamous-cell carcinoma. The optimal treatment for rectal squamous-cell carcinoma is not well established. OBJECTIVE The purpose of this work was to assess the efficacy of nonoperative strategies in the management of primary rectal squamous-cell carcinoma. DESIGN We retrospectively reviewed data from all of the patients with documented rectal squamous-cell carcinoma who were treated with conservative strategies in a single institution. Concomitant radiochemotherapy was proposed to all except 1 patient. The remaining patient was treated by radiotherapy alone given his impaired functional status. All of the patients were treated with conformal or intensity-modulated radiation therapy. Surgical resection was reserved for persistent disease or relapse. SETTING This study was conducted in a single tertiary institution. MAIN OUTCOME MEASURES After a mean follow-up of 56 months, 2 patients experienced relapse and no patients died. RESULTS Eleven patients were included in the series. The clinical response to radiotherapy was complete for 7 patients. The remaining 4 patients underwent salvage surgery. The pathologic response was incomplete for 2 of the 4 patients. One recurrence occurred outside the field of radiotherapy and was successfully treated by radiotherapy. The second was a local recurrence, which occurred on a patient who was treated with radiotherapy alone. LIMITATIONS The number of patients included in this retrospective series was limited because of the rarity of the disease. Patients were treated with nonhomogeneous conservative strategies because of modification in the therapeutic strategy for anal squamous-cell carcinoma and of the adaptation of the treatment to patient comorbidities and functional status. CONCLUSIONS This series demonstrates that good results can be obtained by using a rectum-conserving strategy. Close follow-up should be maintained, with the use of salvage surgery reserved only for persistent disease or relapse (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A155).
Collapse
|
|
29
|
Rectal Cancer. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
30
|
Ihn MH, Kim YH, Kim DW, Oh HK, Lee SY, Park JT, Son IT, Park JH, Lee YJ, Kim JW, Lee KW, Kim JH, Shin E, Lee HS, Ahn S, Kang SB. Effects of Preoperative Chemoradiotherapy on the Likelihood of Sphincter Preservation Surgery in Locally Advanced Distal Rectal Cancer: A Longitudinal Study Based on Pelvic Magnetic Resonance Imaging. Ann Surg Oncol 2014; 22:2159-67. [PMID: 25503346 DOI: 10.1245/s10434-014-4286-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Indexed: 12/29/2022]
Abstract
BACKGROUND It is unclear whether preoperative chemoradiotherapy (pCRT) increases the rate of sphincter-preserving surgery (SPS), avoiding abdominoperineal resection (APR), for the treatment of distal rectal cancer. We examined whether pCRT increases the likelihood of SPS based on changes in tumor height using pelvic magnetic resonance imaging (MRI). METHODS Between January 2009 and December 2013, 105 patients underwent long-course pCRT for locally advanced distal rectal cancer (≤5 cm from the anal verge) and were included in this study. The surgical procedures were analyzed in terms of radiologic findings, including the distance from the inferior margin of tumor to the superior margin of the anorectal ring (tumor height) measured by pelvic MRI before and after pCRT. RESULTS Eighty-six (81.9 %) patients underwent SPS. Overall clinical downstaging occurred in 48 (45.7 %) patients. Tumor height increased significantly after pCRT (from 15.0 ± 15.3 to 18.1 ± 16.9 mm, change 3.1 ± 9.7 mm, p = 0.01). The mean change in tumor height was not significantly different between patients who underwent SPS or APR (mean change 3.3 ± 9.6 vs. 2.3 ± 10.5 mm, p = 0.68). The mean change was significantly greater in the double-stapled anastomosis group than in the handsewn anastomosis group (mean change 5.6 ± 9.9 vs. -0.6 ± 8.6 mm, p = 0.02). CONCLUSIONS This was the first MRI-based longitudinal study to show that pCRT does not appear to increase the likelihood of SPS in locally advanced distal rectal cancer, although it could improve the potential of double-stapled anastomoses.
Collapse
Affiliation(s)
- Myong Hoon Ihn
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Bénézery K, Frin A, Gal J, Zhou F, François E, Benchimol D, Marcié S, Gérard J. Conservation du rectum dans le traitement des adénocarcinomes rectaux de stade T 1-2-3 Nx M0 : rôle de la radiothérapie de contact, expérience niçoise sur 60 patients. Cancer Radiother 2014. [DOI: 10.1016/j.canrad.2014.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
|
|
32
|
Vignali A, Nardi PD. Multidisciplinary treatment of rectal cancer in 2014: Where are we going? World J Gastroenterol 2014; 20:11249-11261. [PMID: 25170209 PMCID: PMC4145763 DOI: 10.3748/wjg.v20.i32.11249] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2014] [Revised: 05/08/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
In the present review we discuss the recent developments and future directions in the multimodal treatment of locally advanced rectal cancer, with respect to staging and re-staging modalities, to the current role of neoadjuvant chemo-radiation and to the conservative and more limited surgical approaches based on tumour response after neoadjuvant combined therapy. When initial tumor staging is considered a high accuracy has been reported for T pre-treatment staging, while preoperative lymph node mapping is still suboptimal. With respect to tumour re-staging, all the current available modalities still present a limited accuracy, in particular in defining a complete response. The role of short vs long-course radiotherapy regimens as well as the optimal time of surgery are still unclear and under investigation by means of ongoing randomized trials. Observational management or local excision following tumour complete response are promising alternatives to total mesorectal excision, but need further evaluation, and their use outside of a clinical trial is not recommended. The preoperative selection of patients who will benefit from neoadjuvant radiotherapy or not, as well as the proper identification of a clinical complete tumour response after combined treatment modalities,will influence the future directions in the treatment of locally advanced rectal cancer.
Collapse
|
|
33
|
Alberda WJ, Burger JWA, Beets-Tan RB, Verhoef C. Challenges in determining the benefits of restaging after chemoradiotherapy for locally advanced rectal cancer. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Wijnand J Alberda
- Erasmus MC Cancer Institute, Department of Surgery, Division of Surgical Oncology, Rotterdam, The Netherlands
| | - Jacobus WA Burger
- Erasmus MC Cancer Institute, Department of Surgery, Division of Surgical Oncology, Rotterdam, The Netherlands
| | - Regina B Beets-Tan
- Maastricht University Medical Center, Department of Radiology, Maastricht, The Netherlands
| | - Cornelis Verhoef
- Erasmus MC Cancer Institute, Department of Surgery, Division of Surgical Oncology, Rotterdam, The Netherlands
| |
Collapse
|
|
34
|
Park IJ, Yu CS. Current issues in locally advanced colorectal cancer treated by preoperative chemoradiotherapy. World J Gastroenterol 2014; 20:2023-2029. [PMID: 24587677 PMCID: PMC3934472 DOI: 10.3748/wjg.v20.i8.2023] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/26/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
In patients with locally advanced rectal cancer, preoperative chemoradiotherapy has proven to significantly improve local control and cause lower treatment-related toxicity compared with postoperative adjuvant treatment. Preoperative chemoradiotherapy followed by total mesorectal excision or tumor specific mesorectal excision has evolved as the standard treatment for locally advanced rectal cancer. The paradigm shift from postoperative to preoperative therapy has raised a series of concerns however that have practical clinical implications. These include the method used to predict patients who will show good response, sphincter preservation, the application of conservative management such as local excision or “wait-and-watch” in patients obtaining a good response following preoperative chemoradiotherapy, and the role of adjuvant chemotherapy. This review addresses these current issues in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy.
Collapse
|
|
35
|
Damin DC, Lazzaron AR. Evolving treatment strategies for colorectal cancer: A critical review of current therapeutic options. World J Gastroenterol 2014; 20:877-887. [PMID: 24574762 PMCID: PMC3921541 DOI: 10.3748/wjg.v20.i4.877] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/22/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Management of rectal cancer has markedly evolved over the last two decades. New technologies of staging have allowed a more precise definition of tumor extension. Refinements in surgical concepts and techniques have resulted in higher rates of sphincter preservation and better functional outcome for patients with this malignancy. Although, preoperative chemoradiotherapy followed by total mesorectal excision has become the standard of care for locally advanced tumors, many controversial matters in management of rectal cancer still need to be defined. These include the feasibility of a non-surgical approach after a favorable response to neoadjuvant therapy, the ideal margins of surgical resection for sphincter preservation and the adequacy of minimally invasive techniques of tumor resection. In this article, after an extensive search in PubMed and Embase databases, we critically review the current strategies and the most debatable matters in treatment of rectal cancer.
Collapse
|
|
36
|
Gerard JP, Benezery K, Doyen J, Francois E. Aims of combined modality therapy in rectal cancer (M0). Recent Results Cancer Res 2014; 203:153-69. [PMID: 25103004 DOI: 10.1007/978-3-319-08060-4_11] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
UNLABELLED OPTIMIZING THE COST/BENEFIT RATIO OF TREATMENT: Evidence Based The aim of a cancer treatment is always to achieve the maximum of cure rate with a minimum of toxicity and best quality of life at an acceptable cost for the society. It is always a multifactorial challenge depending on the patient, the tumor, the doctor, and the society cultural and financial backgrounds. The goal is to find the best cost/benefit ratio between all possible strategies in agreement with a well-informed patient. In rectal cancer (M0) surgery is the cornerstone of treatment. Combined modality therapies aim at optimizing the cost/benefit ratio of possible strategies and only randomized trials can bring strong evidence regarding their results and recommendations. LESSONS FROM RANDOMIZED TRIALS: quite modest During the past decades many phase III trials have shown that: (1) neoadjuvant treatment even with "TME" surgery was better than adjuvant, (2) chemoradiotherapy (CRT) was better than RT alone, (3) long course CRT was probably more efficient (in terms of ypCR) than short course (25/5), and (4) capecitabine was as efficient as 5 FU but oxaliplatin was not adding benefit. Overall, the gains of nCRT remain modest and it is mainly a reduction in local relapse not exceeding 5 %, but no benefit in survival and neither in sphincter saving surgery has been proven. The way forwards organ preservation in case of CCR. Local control: can probably be improved for T4 tumors by RT dose escalation. Survival: can be increased by innovative medical treatment either before or after surgery. TOXICITY may be reduced by a less aggressive treatment in elderly. Conservative treatment: A new field of clinical research is to achieve "organ preservation" (and not only sphincter saving). To modify the surgical approach and preserve the whole rectum, neoadjuvant treatment must achieve safely a clinical complete response. As rectal adenocarcinoma is a relatively radioresistant tumor endocavitary irradiation (contact X-Ray) is a promising safe approach and this hypothesis will be addressed by the OPERA randomized trial.
Collapse
Affiliation(s)
- J P Gerard
- Departement of Radiation Oncology, Centre Antoine-Lacassagne, 33 Avenue de Valombrose, 01689, Nice Cedex 2, France,
| | | | | | | |
Collapse
|
|
37
|
Wibe A, Law WL, Fazio V, Delaney CP. Tailored rectal cancer treatment--a time for implementing contemporary prognostic factors? Colorectal Dis 2013; 15:1333-42. [PMID: 23758978 DOI: 10.1111/codi.12317] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2012] [Accepted: 02/03/2013] [Indexed: 12/26/2022]
Abstract
AIM To report data supporting the development of tailored treatment strategies for rectal cancer. METHOD A comprehensive review of the literature on the impact of prognostic factors cur-rently not included in international guidelines in rectal cancer management. RESULTS There is considerable variation in treatment guidelines for rectal cancer worldwide, especially for Stage II and Stage III disease. Long-term side effects of chemoradiotherapy are not considered in any guideline. Detailed knowledge, and the prognostic impact, of the circumferential resection margin, tumour grade and venous invasion should be factored into the development of a treatment strategy. CONCLUSION Factors additional to the TNM system should improve decision making for contemporary rectal cancer treatment. Optimized radiological and pathological evaluations, and a focus on detailed clinical factors, should be the basis for treatment decisions. International guidelines should consider all known prognostic factors for long-term oncological and functional outcomes.
Collapse
Affiliation(s)
- A Wibe
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Surgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | | | | | | |
Collapse
|
|
38
|
Dholakia AS, Hacker-Prietz A, Wild AT, Raman SP, Wood LD, Huang P, Laheru DA, Zheng L, De Jesus-Acosta A, Le DT, Schulick R, Edil B, Ellsworth S, Pawlik TM, Iacobuzio-Donahue CA, Hruban RH, Cameron JL, Fishman EK, Wolfgang CL, Herman JM. Resection of borderline resectable pancreatic cancer after neoadjuvant chemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships. ACTA ACUST UNITED AC 2013; 2:413-425. [PMID: 25755849 DOI: 10.1007/s13566-013-0115-6] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Neoadjuvant therapy increases rates of margin-negative resection of borderline resectable pancreatic ductal adenocarcinoma (BL-PDAC). Criteria for BL-PDAC resection following neoadjuvant chemotherapy and radiation therapy (NCRT) have not been clearly defined. METHODS Fifty consecutive patients with BL-PDAC who received NCRT from 2007 to 2012 were identified. Computed tomography (CT) scans pre- and post-treatment were centrally reviewed. RESULTS Twenty-nine patients (58 %) underwent resection following NCRT, while 21 (42 %) remained unresected. Patients selected for and successfully undergoing resection were more likely to have better performance status and absence of the following features on pre- and post-treatment CT: superior mesenteric vein/portal vein encasement, superior mesenteric artery involvement, tumor involvement of two or more vessels, and questionable/overt metastases (all p <0.05). Tumor volume and degree of tumor-vessel involvement did not significantly change in both groups after NCRT (all p > 0.05). The median overall survival was 22.9 months in resected versus 13.0 months in unresected patients (p < 0.001). Of patients undergoing resection, 93 % were margin-negative, 72 % were node-negative, and 54 % demonstrated moderate pathologic response to NCRT. CONCLUSION Apparent radiographic extent of vascular involvement does not change significantly after NCRT. Patients without metastatic disease should be chosen for surgical exploration based on adequate performance status and lack of disease progression.
Collapse
Affiliation(s)
- Avani S Dholakia
- Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231, USA
| | - Amy Hacker-Prietz
- Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231, USA
| | - Aaron T Wild
- Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231, USA
| | - Siva P Raman
- Department of Radiology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 601 N. Broadway, Baltimore, MD 21231, USA
| | - Laura D Wood
- Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 2242, Baltimore, MD 21231, USA
| | - Peng Huang
- Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 550 N. Broadway, Suite 1103, Baltimore, MD 21205, USA
| | - Daniel A Laheru
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21287, USA
| | - Lei Zheng
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21287, USA
| | - Ana De Jesus-Acosta
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21287, USA
| | - Dung T Le
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21287, USA
| | - Richard Schulick
- Department of Surgery, University of Colorado, 12631 E. 17th Avenue, Suite 6117, Aurora, CO 80045, USA
| | - Barish Edil
- Department of Surgery, University of Colorado, 12631 E. 17th Avenue, Suite 6117, Aurora, CO 80045, USA
| | - Susannah Ellsworth
- Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231, USA
| | - Timothy M Pawlik
- Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA
| | - Christine A Iacobuzio-Donahue
- Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 2242, Baltimore, MD 21231, USA
| | - Ralph H Hruban
- Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 2242, Baltimore, MD 21231, USA
| | - John L Cameron
- Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA
| | - Elliot K Fishman
- Department of Radiology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 601 N. Broadway, Baltimore, MD 21231, USA
| | - Christopher L Wolfgang
- Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA
| | - Joseph M Herman
- Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231, USA
| |
Collapse
|
|
39
|
Impact of obesity on operation performed, complications, and long-term outcomes in terms of restoration of intestinal continuity for patients with mid and low rectal cancer. Dis Colon Rectum 2013; 56:689-97. [PMID: 23652741 DOI: 10.1097/dcr.0b013e3182880ffa] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The impact of obesity per se on the surgical strategy, ie, sphincter sacrifice (abdominoperineal resection) vs sphincter-preserving resection, outcomes, and long-term maintenance of intestinal continuity has been poorly studied in patients with mid and low rectal cancer. OBJECTIVE The aim of this study is to compare the outcomes and long-term maintenance of intestinal continuity for obese and nonobese patients treated surgically for mid and low rectal cancers. DESIGN This is a retrospective cohort study from a prospectively collected database. SETTING The investigation took place in a high-volume specialized colorectal surgery department. PATIENTS All patients who underwent curative surgery for mid or low rectal adenocarcinoma at a single institution from 1976 to 2011 were identified. MAIN OUTCOME MEASURES Obese (BMI ≥ 30 kg/m) and nonobese patients were matched 1:2 for age, sex, ASA class, location, and stage of tumor. Demographics, use of neoadjuvant chemoradiotherapy, operative and perioperative outcomes, pathology, long-term outcomes including oncologic outcomes, and whether restoration of intestinal continuity was obtained were compared. RESULTS One hundred fifty-seven obese patients and 314 nonobese patients were included in the study. The groups were similar for matched characteristics. The use of neoadjuvant chemoradiotherapy (p = 0.048) and anastomotic leak (p = 0.0003) rates were higher in obese patients. A similar proportion of nonobese and obese patients underwent sphincter-preserving resection (p > 0.99), and postoperative hospital stay (p = 0.23), 30-day postoperative reoperation (p = 0.83), mortality (p > 0.99), and readmissions (p = 0. 13) were similar. The obese and nonobese groups had similar overall (p = 0.61) and disease-free survival (p = 0.74) at a mean follow-up of 5 years for both groups. LIMITATIONS This study was limited by its retrospective and nonrandomized nature. CONCLUSION At a high-volume specialized colorectal unit, proctectomy can be performed in obese patients with similar long-term oncologic outcomes and ability to restore intestinal continuity in comparison with nonobese patients. Proctectomy in obese patients, however, is associated with an increased risk of anastomotic leak in comparison with nonobese patients.
Collapse
|
|
40
|
Is tailoring treatment of rectal cancer the only true benefit of long-course neoadjuvant chemoradiation? Dis Colon Rectum 2013; 56:264-6. [PMID: 23303157 DOI: 10.1097/dcr.0b013e318277e8e4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
|
|
41
|
Management of distal rectal cancer: results from a national survey. Updates Surg 2013; 65:43-52. [PMID: 23335049 DOI: 10.1007/s13304-012-0192-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Accepted: 12/17/2012] [Indexed: 02/07/2023]
Abstract
Owing to the complexity of distal rectal cancer its management requires a multidisciplinary approach. The diagnosis and the response after neoadjuvant chemoradiotherapy are not easy to assess and therefore the surgical approach is heterogeneous. The purpose of this survey is to evaluate the experiences of members of the Italian Society of Surgery in diagnosis and treatment strategies for rectal cancer and compare it with international practice. A questionnaire was devised comprising 18 questions with 11 sub-items making a total of 29 questions and submitted online to all the 2,500 members of the SIC starting from July 2010. The survey was completed in June 2011. The overall response rate was 17.8 % (444). The majority of the Italian surgeons' responses were in line with the international consensus reflecting the complex management of distal rectal cancer. Other opinions, especially those on staging, diverge from the common view of MRI being the gold standard in the assessment of loco-regional diffusion of the disease and on the superiority of FDG PET-CT versus CT for systemic staging. The timing for the re-staging and for surgery following neoadjuvant chemoradiotherapy does not reflect the international opinion. Italian surgeons are also exposed to the common difficulties encountered internationally in the management of distal rectal cancer. Probably, the implementation of an Italian rectal cancer registry and of many national and international multicentre studies may improve the management of rectal cancer in Italy.
Collapse
|
|
42
|
de Manzini N, Leon P, Tarchi P, Giacca M. Surgical Strategy: Indications. Updates Surg 2013. [DOI: 10.1007/978-88-470-2670-4_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
43
|
Lim SB, Kim JC. Surgical issues in locally advanced rectal cancer treated by preoperative chemoradiotherapy. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2012; 84:1-8. [PMID: 23323229 PMCID: PMC3539104 DOI: 10.4174/jkss.2013.84.1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/07/2012] [Revised: 11/10/2012] [Accepted: 11/11/2012] [Indexed: 12/16/2022]
Abstract
The standard treatment for patients with locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. This approach is supported by randomized trials, but there are still many unanswered questions about the multimodal management of rectal cancer. In surgical terms, these include the optimal time interval between completion of chemoradiotherapy and surgery; adequate distal resection margin and circumferential radial margin; sphincter preservation; laparoscopic surgery; and conservative management, including a 'wait and see' policy and local excision. This review considers these controversial issues in preoperative chemoradiotherapy.
Collapse
Affiliation(s)
- Seok-Byung Lim
- Department of Surgery, Asan Medical Center, Institute of Innovative Cancer Research, University of Ulsan College of Medicine, Seoul, Korea
| | | |
Collapse
|
|
44
|
Katz MHG, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, Wang H, Abbruzzese J, Pisters PWT, Vauthey JN, Charnsangavej C, Tamm E, Crane CH, Balachandran A. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012; 118:5749-56. [PMID: 22605518 DOI: 10.1002/cncr.27636] [Citation(s) in RCA: 375] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Revised: 04/06/2012] [Accepted: 04/09/2012] [Indexed: 02/03/2023]
Abstract
BACKGROUND Experience with preoperative therapy for other cancers has led to an assumption that borderline resectable pancreatic cancers can be converted to resectable cancers with preoperative therapy. In this study, the authors sought to determine the rate at which neoadjuvant therapy is associated with a reduction in the size or stage of borderline resectable tumors. METHODS Patients who had borderline resectable pancreatic cancer and received neoadjuvant therapy before potentially undergoing surgery at the authors' institution between 2005 and 2010 were identified. The patients' pretreatment and post-treatment pancreatic protocol computed tomography images were rereviewed to determine changes in tumor size or stage using modified Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) and standardized anatomic criteria. RESULTS The authors identified 129 patients who met inclusion criteria. Of the 122 patients who had their disease restaged after receiving preoperative therapy, 84 patients (69%) had stable disease, 15 patients (12%) had a partial response to therapy, and 23 patients (19%) had progressive disease. Although only 1 patient (0.8%) had their disease downstaged to resectable status after receiving neoadjuvant therapy, 85 patients (66%) underwent pancreatectomy. The median overall survival duration for all 129 patients was 22 months (95% confidence interval, 14-30 months). The median overall survival duration for the patients who underwent pancreatectomy was 33 months (95% confidence interval, 25-41 months) and was not associated with RECIST response (P = .78). CONCLUSIONS Radiographic downstaging was rare after neoadjuvant therapy, and RECIST response was not an effective treatment endpoint for patients with borderline resectable pancreatic cancer. The authors concluded that these patients should undergo pancreatectomy after initial therapy in the absence of metastases.
Collapse
Affiliation(s)
- Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Towards a "Lyon molecular signature" to individualize the treatment of rectal cancer. Prognostic analysis of a prospective cohort of 94 rectal cancers T1-2-3 Nx MO to be the basis of a molecular signature. Cancer Radiother 2012; 16:688-96. [PMID: 23153504 DOI: 10.1016/j.canrad.2012.09.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2011] [Revised: 07/25/2011] [Accepted: 09/30/2012] [Indexed: 02/07/2023]
Abstract
PURPOSE In 1998 a translational research was initiated in Lyon aiming at identifying a prognostic "biomolecular signature" in rectal cancer. This paper presents the clinical outcome of the patients included in this study. PATIENTS AND METHODS A total of 94 patients were included between 1998 and 2001. A staging with rectoscopy and biopsies was performed before treatment. In case of surgery, the operative specimen was analysed to evaluate the pathological response. There were two types of treatment: neoadjuvant radiotherapy (with or without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy alone with 'contactherapy' often associated with external beam radiotherapy (18 patients). RESULTS The patients had a mean age of 63years. Stage was T1: 4, T2: 24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8years with a rate of distant metastases of 29%. Rate of local recurrence at 8years was 6% in the neoadjuvant group and 16% in the radiotherapy group with an overall 8years survival in both groups respectively: 64% and 53%. There was a trend towards more metastases in cT3, tumour diameter above 4cm, circumferential extension. There was a significant increase in the risk of metastases for ypT3, ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly associated with a high rate of metastases (55%; P=0.0003). CONCLUSION The rate of distant metastases is a major prognostic factor. These clinical results will serve as the base line to identify a "biomolecular signature" which could complement the TN(M) classification.
Collapse
|
|
46
|
Kosinski L, Habr-Gama A, Ludwig K, Perez R. Shifting concepts in rectal cancer management: a review of contemporary primary rectal cancer treatment strategies. CA Cancer J Clin 2012; 62:173-202. [PMID: 22488575 DOI: 10.3322/caac.21138] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The management of rectal cancer has transformed over the last 3 decades and continues to evolve. Some of these changes parallel progress made with other cancers: refinement of surgical technique to improve organ preservation, selective use of neoadjuvant (and adjuvant) therapy, and emergence of criteria suggesting a role for individually tailored therapy. Other changes are driven by fairly unique issues including functional considerations, rectal anatomic features, and surgical technical issues. Further complexity is due to the variety of staging modalities (each with its own limitations), neoadjuvant treatment alternatives, and competing strategies for sequencing multimodal treatment even for nonmetastatic disease. Importantly, observations of tumor response made in the era of neoadjuvant therapy are reshaping some traditionally held concepts about tumor behavior. Frameworks for prioritizing and integrating complex data can help to formulate treatment plans for patients.
Collapse
Affiliation(s)
- Lauren Kosinski
- Division of Colorectal Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
| | | | | | | |
Collapse
|
|
47
|
Pach R, Kulig J, Richter P, Gach T, Szura M, Kowalska T. Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer--treatment results at 5-year follow-up. Langenbecks Arch Surg 2011; 397:801-7. [PMID: 22170083 PMCID: PMC3349846 DOI: 10.1007/s00423-011-0890-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2011] [Accepted: 11/30/2011] [Indexed: 12/15/2022]
Abstract
Purpose The purpose of this study was to establish the influence of time interval between preoperative hyperfractionated radiotherapy (5 × 5 Gy) and surgery on long-term overall survival (5 years) and recurrence rate in patients with locally advanced rectal cancer operated on according to total mesorectal excision technique. Methods The treatment group comprised 154 patients with locally advanced rectal cancer who were operated on between 1999 and 2006 in the 1st Department of General Surgery, Jagiellonian University, Cracow, Poland. The data on survival has been systematically collected until 31st of December 2010. In addition, the following aspects were analyzed: the significance of time interval between the end of radiotherapy and surgical treatment and its influence on downsizing, downstaging, rate of curative resections, and sphincter-sparing procedures. Patients were qualified to preoperative radiotherapy 5 × 5 Gy and then randomly assigned to subgroups with different time intervals between radiotherapy and surgery: one subgroup consisted of 77 patients operated on 7–10 days after the end of irradiation, and the second subgroup consisted of 77 patients operated on after 4–5 weeks. Both groups were homogenous in sex, age, cancer stage and localization, distal and circumferential resection margins, and number of resected lymph nodes. Results The 5-year survival rate in patients operated on 7–10 days after irradiation was 63%, whereas in those operated on after 4–5 weeks, it was 73%—the difference was not statistically significant (log rank, p = 0.24). A statistically significant increase in 5-year survival rate was observed only in patients with downstaging after radiotherapy—90% in comparison with 60% in patients without response to neoadjuvant treatment (log rank, p = 0.004). Recurrence was diagnosed in 13.2% of patients. A lower rate of systemic recurrence was observed in patients operated on 4–5 weeks after the end of irradiation (2.8% vs. 12.3% in the subgroup with a shorter interval, p = 0.035). No differences in local recurrence rates were observed in both subgroups of irradiated patients (p = 0.119). The longer time interval between radiotherapy and surgery resulted in higher downstaging rate (44.2% vs. 13% in patients with a shorter interval, p = 0.0001) although it did not increase the rate of sphincter-saving procedures (p = 0.627) and curative resections (p = 0.132). Conclusions
Improved 5-year survival rate is observed only in patients with downstaging after preoperative irradiation dose of 25 Gy. Longer time interval after preoperative radiotherapy 25 Gy does not improve the rate of sphincter-saving procedures and curative resections (R0) despite higher downstaging rate observed in this regimen.
Collapse
Affiliation(s)
- Radoslaw Pach
- 1st Department of General Surgery, Jagiellonian University, Cracow, Poland.
| | | | | | | | | | | |
Collapse
|
|
48
|
Garajová I, Di Girolamo S, de Rosa F, Corbelli J, Agostini V, Biasco G, Brandi G. Neoadjuvant treatment in rectal cancer: actual status. CHEMOTHERAPY RESEARCH AND PRACTICE 2011; 2011:839742. [PMID: 22295206 PMCID: PMC3263610 DOI: 10.1155/2011/839742] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/30/2010] [Revised: 06/20/2011] [Accepted: 06/28/2011] [Indexed: 02/07/2023]
Abstract
Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas.
Collapse
Affiliation(s)
- Ingrid Garajová
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| | - Stefania Di Girolamo
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| | - Francesco de Rosa
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| | - Jody Corbelli
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| | - Valentina Agostini
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| | - Guido Biasco
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| | - Giovanni Brandi
- Department of Hematology and Oncology Sciences “L. A. Seragnoli”, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy
| |
Collapse
|
|
49
|
Créhange G, Bosset JF, Maingon P. [Preoperative radiochemotherapy for rectal cancer: forecasting the next steps through ongoing and forthcoming studies]. Cancer Radiother 2011; 15:440-4. [PMID: 21802334 DOI: 10.1016/j.canrad.2011.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2011] [Accepted: 05/24/2011] [Indexed: 01/09/2023]
Abstract
Protracted preoperative radiochemotherapy with a 5-FU-based scheme, or a short course of preoperative radiotherapy without chemotherapy, are the standard neoadjuvant treatments for resectable stage II-III rectal cancer. Local failure rates are low and reproducible, between 6 and 15% when followed with a "Total Mesorectal Excision". Nevertheless, the therapeutic strategy needs to be improved: distant metastatic recurrence rates remain stable around 30 to 35%, while both sphincter and sexual sequels are still significant. The aim of the present paper was to analyse the ongoing trials listed on the following search engines: the Institut National du Cancer in France, the National Cancer Institute and the National Institute of Health in the United States, and the major cooperative groups. Keywords for the search were: "rectal cancer", "preoperative radiotherapy", "phase II-III", "preoperative chemotherapy", "adjuvant chemotherapy" and "surgery". Twenty-three trials were selected and classified in different groups, each of them addressing a question of strategy: (1) place of adjuvant chemotherapy; (2) optimization of preoperative radiotherapy; (3) evaluation of new radiosensitization protocols and/or neoadjuvant chemotherapy; (4) optimization of techniques and timing of surgery; (5) place of radiotherapy for non resectable or metastatic tumors.
Collapse
MESH Headings
- Adenocarcinoma/drug therapy
- Adenocarcinoma/radiotherapy
- Adenocarcinoma/surgery
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal, Humanized
- Antimetabolites, Antineoplastic/administration & dosage
- Antimetabolites, Antineoplastic/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Camptothecin/administration & dosage
- Camptothecin/analogs & derivatives
- Capecitabine
- Cetuximab
- Chemotherapy, Adjuvant
- Clinical Trials, Phase II as Topic/statistics & numerical data
- Clinical Trials, Phase III as Topic
- Combined Modality Therapy
- Deoxycytidine/administration & dosage
- Deoxycytidine/analogs & derivatives
- Fluorouracil/administration & dosage
- Fluorouracil/analogs & derivatives
- Forecasting
- Humans
- Irinotecan
- Leucovorin/administration & dosage
- Multicenter Studies as Topic/statistics & numerical data
- Neoadjuvant Therapy
- Organoplatinum Compounds/administration & dosage
- Oxaliplatin
- Radiation-Sensitizing Agents/administration & dosage
- Radiotherapy, Conformal/adverse effects
- Radiotherapy, Conformal/methods
- Randomized Controlled Trials as Topic/statistics & numerical data
- Rectal Neoplasms/drug therapy
- Rectal Neoplasms/radiotherapy
- Rectal Neoplasms/surgery
- Time Factors
- Treatment Outcome
Collapse
Affiliation(s)
- G Créhange
- Département de radiothérapie, centre Georges-François-Leclerc, 1, rue du Professeur-Marion, 21000 Dijon, France.
| | | | | |
Collapse
|