VOLUME
32
䡠
NUMBER
15
䡠
MAY
20
2014
JOURNAL OF CLINICAL ONCOLOGY
E
D
I
T
O
R
I
A
L
Tumor Regression Grading in Rectal Cancer: Is It Time to Move Forward? Vincenzo Valentini, Policlinico A. Gemelli–Universita` Cattolica S. Cuore, Rome, Italy Bruce D. Minsky, MD Anderson Cancer Center, Houston, TX See accompanying article on page 1554
In contrast with adjuvant colon cancer trials where 2-year results are adequate, patients with rectal cancer receiving preoperative chemoradiotherapy can experience late failures.1 Long-term follow-up of the German CAO/ARO/AIO (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the German Cancer Society)-94 Rectal Cancer Trial reveals a continuous increase in local recurrence up to 10 years. Therefore, there is substantial interest in short-term surrogate end points. Many preoperative chemoradiotherapy trials have explored the use of pathologic complete response rate (pCR) and/or tumor regression grading (TRG) as primary end points. The lack of standard definitions of TRG, various intervals between the end of chemoradiotherapy, and the lack of pathology quality control have made the data challenging to interpret. In the article that accompanies this editorial, Fokas et al2 present a well designed and robust analysis of the prognostic impact of TRG in patients with rectal adenocarcinoma treated by preoperative chemoradiotherapy and total mesorectal excision. The study includes patients enrolled on the German CAO/ARO/AIO-94 randomized phase III trial of preoperative versus postoperative chemoradiotherapy. The authors report that, by multivariable analysis, TRG is a significant, independent prognostic factor for metastasis-free and disease-free survival (DFS). Previously published studies from other groups have reported similar results, including a significant impact of TRG on local control, incidence of metastasis, DFS, and overall survival (OS). This study, however, differs from others reported in the literature because of the homogeneity of the surgical and adjuvant treatments performed, large number of prospectively enrolled patients, and long follow-up (median, 132 months).2 Is response a reasonable surrogate end point? The analysis conducted by Bonnetain et al3 showed that pCR predicted local recurrence, progression-free survival (PFS) or OS poorly. They suggested that pCR could be used as primary end point for phase II rectal cancer trials or as an intermediate end point in futility stopping rules for phase III trials when OS or PFS is the final end point. If new phase III trials need earlier end points than OS, they recommended using PFS, otherwise they discourage its use as definitive end points. Similarly Valentini et al4 pooled data from five large European randomized clinical trials for locally advanced rectal cancer (N ⫽ 2,795). The ad hoc comparison between OS according to pCR and 1534
© 2014 by American Society of Clinical Oncology
2-year DFS showed that the latter had a stronger prognostic impact. They suggested that 2-year DFS could be considered as an intermediate end point in future trials. The evaluation of prognostic relevance of TRG score is also affected by the method of pathological evaluation. In the present trial, the standardized five-point TRG was used based on the work of Dworak et al.5 This is one of several TRG methods, and there is no consensus for a universally approved regression classification. The macroscopic examination of the specimen to evaluate TRG score is critical and could affect its prognostic significance. A protocol to assess and to classify a tumor according to a TRG score has been recommended from Quirke et al.6 The Guidelines of the Royal College of Pathologists in the United Kingdom have gained widespread acceptance as the minimum standard for reporting. There are a number of suggested methods for assessing tumor regression after preoperative therapy. The College of American Pathologists Guidelines recently suggest that tumor response should be graded on a scale of 0 (complete response; no viable cancer cells) to 3 (poor response; minimal or no regression, extensive residual cancer).7 The various classification systems proposed for rectal cancer need to be cross-validated for their predictive value and reproducibility in a broader setting. It should be emphasized that TRG scores have not accounted for the possible involvement of lymph nodes. The correlation among the different values of TRG and the incidence of positive nodes is an area of active investigation.8,9 A detailed description of the method of pathological assessment and the selected TRG scoring system should be clearly identified. The presence of a favorable TRG after radical surgery, especially an abdominal perineal resection which requires a permanent stoma, challenges us to consider alternatives for our patients. New clinical trials are exploring the option of more conservative surgery such as local excision10 or forgoing surgery completely using the watch-andwait approach in patients who achieve a favorable response to preoperative therapy.11,12 For example, the 2013 series by Habr-Gama et al11 reported the results of this approach in 70 patients with tumors located at a maximum of 7 cm from the anal verge who underwent highresolution magnetic resonance imaging (MRI) or three-dimensional transrectal ultrasound and had cT2-4 or N1-2 disease. If there was no residual abnormality by proctoscopy and restaging was negative 10 weeks after chemoradiotherapy, patients were staged as initial clinical complete response (cCR) and placed on the watch-and-wait strategy Journal of Clinical Oncology, Vol 32, No 15 (May 20), 2014: pp 1534-1536
Information downloaded from jco.ascopubs.org and provided by at Queen Mary, University of London on July 8, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 138.37.211.113
Editorial
which included frequent exams and repeat imaging every 2 to 6 months. If at 10 weeks there was a residual abnormality patients underwent a local excision and if there was a ypT0 disease they were also placed on the watch-and-wait strategy. Patients in these two groups who had no evidence of disease at 1 year were staged as sustained cCR. All other patients (defined as incomplete responders) underwent salvage radical surgery. There were 69 evaluable patients with a minimum of 12 months follow-up after the completion of chemoradiotherapy. With a total median follow-up of 53 months, 51% of patients who completed chemoradiotherapy had a sustained cCR the 3-year survival was 94%. A prospective Italian cooperative phase II trial (Leader Trial) assessed the impact of a transanal local excision, which provides an evaluation of TRG, on local recurrence in patients with rectal cancer who had a major clinical response after preoperative chemoradiotherapy.10 Patients with clinical MRI-based cT3 or low-lying cT2, cN0-1 disease with a major clinical response after a preoperative chemoradiotherapy underwent a full-thickness transanal local excision. Patients staged as TRG1-2 were observed, while the remaining were recommended to undergo a total mesorectal excision. The study group included 63 patients. With a median follow-up of 36 months, the estimated cumulative 3-year OS, DFS, and local DFS were 91.5% (95% CI, 75.9% to 97.2%), 91.0% (95% CI, 77.0% to 96.6%), and 96.9% (95% CI, 80.3% to 99.5%), respectively. Few studies have examined the long-term impact on the quality of life and functional outcome in patients who undergo a local excision or a nonoperative approach based on a favorable TRG.13 The benefits of conservative surgery need to be examined in the context of these clinical outcomes. There are still impediments using response to select patients for a conservative surgical approach. The challenge is identifying a surrogate noninvasive method to surgery to accurately identify patients who have achieved a favorable TRG. Current methods include endoscopy and physical exam, ultrasound, computed tomography, MRI, and positron emission tomography, either alone or in combination. Further refinements in imaging may improve the selection process. In addition, prediction models integrating imaging data with clinical variables have significantly increased the prediction for achieving a pCR.14 Another potential application of TRG would be to help select patients for postoperative adjuvant chemotherapy following preoperative chemoradiotherapy. A subgroup analysis of European Organisation for Research and Treatment of Cancer (EORTC) trial 22921 revealed that patients who responded to preoperative chemoradiotherapy had a survival benefit from postoperative chemotherapy.15 Unfortunately, TRG data were not collected in this trial. As an alternative, Valentini et al16 proposed the use of nomograms based on clinical features, pathological staging, and treatment factors to support the decision of adjuvant chemotherapy in multidisciplinary groups. There remains considerable controversy in some European countries regarding its use. An international consensus conference failed to reach a definitive recommendation.17 Although the data are impressive, the TRG score still requires surgery and it is based on pathologic evaluation. As emphasized by Fokas et al,2 it would be helpful to better understand the biologic mechanisms explaining why more locally responsive tumors are less likely to develop distant metastases. Other promising approaches include the use of molecular imaging performed during the different www.jco.org
treatment stages, integrated with clinical data and laboratory tests, possibly aimed at the development of predictive models for clinical decision support.18 In conclusion, data from Fokas et al2 offer solid evidence of the independent prognostic value of TRG following preoperative chemoradiotherapy for rectal cancer. However, the prognostic and predictive significance of TRG is still affected by uncertainties such as limited end points and the quality and heterogeneity of histological data. There are opportunities for future trials to examine the impact of TRG on specific relevant-to-the-patient goals, such as reduction of surgery extent or need for adjuvant therapies. These trials will require stratification according to pretreatment staging and sphincter function, quality of life, and the type of neoadjuvant therapy. When available, large databases may offer some guidance as to the prognostic and predictive impact of TRG. While we await these additional studies, TRG provides a valuable tool to assist in clinical decision making. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. AUTHOR CONTRIBUTIONS
Manuscript writing: All authors Final approval of manuscript: All authors REFERENCES 1. Sargent DJ, Patiyil S, Yothers G, et al: End points for colon cancer adjuvant trials: Observations and recommendations based on individual patient data from 20,898 patients enrolled onto randomized trials from the ACCENT Group. J Clin Oncol 25:4569-4574, 2007 2. Fokas E, Liersch T, Fietkau R, et al: Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: Updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:15541562, 2014 3. Bonnetain F, Bosset JF, Gerard JP, et al: What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question? Eur J Cancer 48:1781-1790, 2012 4. Valentini V, Cellini F, Barba MC, et al: Do Different Populations of Rectal Cancer Exist? in Valentini V, Schmoll HJ, van de Velde CJH (eds): Multidisciplinary Management of Rectal Cancer Questions and Answers, Berlin Heidelberg, Germany, Springer-Verlag, 2012, pp 49-55 5. Dworak O, Keilholz L, Hoffmann A: Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19-23, 1997 6. Quirke P, Williams GT. Minimum Dataset for Colorectal Cancer Histopathology Reports. London, United Kingdom, Royal College of Pathologists, 1998, pp 1-27 7. Washington MK, Berlin J, Branton P, et al: Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. Arch Pathol Lab Med 133:1539-1551, 2009 8. Vecchio FM, Valentini V, Minsky BD, et al: The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 62:752-760, 2005 9. Huebner M, Wolff BG, Smyrk TC, et al: Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg 36:675-683, 2012 10. Pucciarelli S, De Paoli A, Guerrieri M, et al: Local excision after preoperative chemoradiotherapy for rectal cancer: Results of a multicenter phase II clinical trial. Dis Colon Rectum 56:1349-1356, 2013 11. Habr-Gama A, Sabbaga J, Gama-Rodrigues J, et al: Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: Are we getting closer to anal cancer management? Dis Colon Rectum 56:11091117, 2013 12. Maas M, Beets-Tan RGH, Lambregts DMJ, et al: Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29:4633-4640, 2011 13. Coco C, Rizzo G, Mattana C, et al: Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer: Short-term morbidity and functional outcome. Surg Endosc 27:2860-2867, 2013
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Queen Mary, University of London on July 8, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 138.37.211.113
1535
Editorial
14. van Stiphout RG, Lammering G, Buijsen J, et al: Development and external validation of a predictive model for pathological complete response of rectal cancer patients including sequential PET-CT imaging. Radiother Oncol 98:126133, 2011 15. Bosset JF, Collette L, Bardet E, et al: Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114-1123, 2006 16. Valentini V, van Stiphout RGPM, Lammering G, et al: Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: Results of a phase II study. J Clin Oncol 29:3163-3172, 2011
17. van de Velde CJ, Boelens PG, Borras JM, et al: EURECCA colorectal: Multidisciplinary management—European consensus conference colon & rectum. Eur J Cancer 50:1.e1-1.e34, 2014 18. Lambin P, van Stiphout RG, Starmans MH, et al: Predicting outcomes in radiation oncology: Multifactorial decision support systems. Nat Rev Clin Oncol 10:27-40, 2013
DOI: 10.1200/JCO.2014.55.4766; published online ahead of print at www.jco.org on April 21, 2014
■ ■ ■
ASCOconnection.org—The Professional Networking Site for the Worldwide Oncology Community ● Expand your professional network and online profile ● Post your own content and news ● Respond to commentary by oncology leaders ● Create working groups on a secure site ● Connect and collaborate with colleagues ● Read exclusive articles and interviews ASCOconnection.org columnists include ASCO President Clifford Hudis, MD; ASCO President-Elect Peter Yu, MD; Past Presidents Sandra M. Swain, MD, Michael P. Link, MD, George W. Sledge Jr, MD, and Douglas W. Blayney, MD; Journal of Oncology Practice Editor-in-Chief John V. Cox, DO, MBA; Editor-in-Chief of the ASCO Educational Book, Don S. Dizon, MD; Editor-in-Chief of ASCO’s Cancer.Net Robert S. Miller, MD; and many other leaders in the oncology community. Log in with your ASCO.org member or guest account to participate.
1536
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Queen Mary, University of London on July 8, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 138.37.211.113
32
䡠
NUMBER
15
䡠
MAY
20
2014
JOURNAL OF CLINICAL ONCOLOGY
E
D
I
T
O
R
I
A
L
Tumor Regression Grading in Rectal Cancer: Is It Time to Move Forward? Vincenzo Valentini, Policlinico A. Gemelli–Universita` Cattolica S. Cuore, Rome, Italy Bruce D. Minsky, MD Anderson Cancer Center, Houston, TX See accompanying article on page 1554
In contrast with adjuvant colon cancer trials where 2-year results are adequate, patients with rectal cancer receiving preoperative chemoradiotherapy can experience late failures.1 Long-term follow-up of the German CAO/ARO/AIO (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the German Cancer Society)-94 Rectal Cancer Trial reveals a continuous increase in local recurrence up to 10 years. Therefore, there is substantial interest in short-term surrogate end points. Many preoperative chemoradiotherapy trials have explored the use of pathologic complete response rate (pCR) and/or tumor regression grading (TRG) as primary end points. The lack of standard definitions of TRG, various intervals between the end of chemoradiotherapy, and the lack of pathology quality control have made the data challenging to interpret. In the article that accompanies this editorial, Fokas et al2 present a well designed and robust analysis of the prognostic impact of TRG in patients with rectal adenocarcinoma treated by preoperative chemoradiotherapy and total mesorectal excision. The study includes patients enrolled on the German CAO/ARO/AIO-94 randomized phase III trial of preoperative versus postoperative chemoradiotherapy. The authors report that, by multivariable analysis, TRG is a significant, independent prognostic factor for metastasis-free and disease-free survival (DFS). Previously published studies from other groups have reported similar results, including a significant impact of TRG on local control, incidence of metastasis, DFS, and overall survival (OS). This study, however, differs from others reported in the literature because of the homogeneity of the surgical and adjuvant treatments performed, large number of prospectively enrolled patients, and long follow-up (median, 132 months).2 Is response a reasonable surrogate end point? The analysis conducted by Bonnetain et al3 showed that pCR predicted local recurrence, progression-free survival (PFS) or OS poorly. They suggested that pCR could be used as primary end point for phase II rectal cancer trials or as an intermediate end point in futility stopping rules for phase III trials when OS or PFS is the final end point. If new phase III trials need earlier end points than OS, they recommended using PFS, otherwise they discourage its use as definitive end points. Similarly Valentini et al4 pooled data from five large European randomized clinical trials for locally advanced rectal cancer (N ⫽ 2,795). The ad hoc comparison between OS according to pCR and 1534
© 2014 by American Society of Clinical Oncology
2-year DFS showed that the latter had a stronger prognostic impact. They suggested that 2-year DFS could be considered as an intermediate end point in future trials. The evaluation of prognostic relevance of TRG score is also affected by the method of pathological evaluation. In the present trial, the standardized five-point TRG was used based on the work of Dworak et al.5 This is one of several TRG methods, and there is no consensus for a universally approved regression classification. The macroscopic examination of the specimen to evaluate TRG score is critical and could affect its prognostic significance. A protocol to assess and to classify a tumor according to a TRG score has been recommended from Quirke et al.6 The Guidelines of the Royal College of Pathologists in the United Kingdom have gained widespread acceptance as the minimum standard for reporting. There are a number of suggested methods for assessing tumor regression after preoperative therapy. The College of American Pathologists Guidelines recently suggest that tumor response should be graded on a scale of 0 (complete response; no viable cancer cells) to 3 (poor response; minimal or no regression, extensive residual cancer).7 The various classification systems proposed for rectal cancer need to be cross-validated for their predictive value and reproducibility in a broader setting. It should be emphasized that TRG scores have not accounted for the possible involvement of lymph nodes. The correlation among the different values of TRG and the incidence of positive nodes is an area of active investigation.8,9 A detailed description of the method of pathological assessment and the selected TRG scoring system should be clearly identified. The presence of a favorable TRG after radical surgery, especially an abdominal perineal resection which requires a permanent stoma, challenges us to consider alternatives for our patients. New clinical trials are exploring the option of more conservative surgery such as local excision10 or forgoing surgery completely using the watch-andwait approach in patients who achieve a favorable response to preoperative therapy.11,12 For example, the 2013 series by Habr-Gama et al11 reported the results of this approach in 70 patients with tumors located at a maximum of 7 cm from the anal verge who underwent highresolution magnetic resonance imaging (MRI) or three-dimensional transrectal ultrasound and had cT2-4 or N1-2 disease. If there was no residual abnormality by proctoscopy and restaging was negative 10 weeks after chemoradiotherapy, patients were staged as initial clinical complete response (cCR) and placed on the watch-and-wait strategy Journal of Clinical Oncology, Vol 32, No 15 (May 20), 2014: pp 1534-1536
Information downloaded from jco.ascopubs.org and provided by at Queen Mary, University of London on July 8, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 138.37.211.113
Editorial
which included frequent exams and repeat imaging every 2 to 6 months. If at 10 weeks there was a residual abnormality patients underwent a local excision and if there was a ypT0 disease they were also placed on the watch-and-wait strategy. Patients in these two groups who had no evidence of disease at 1 year were staged as sustained cCR. All other patients (defined as incomplete responders) underwent salvage radical surgery. There were 69 evaluable patients with a minimum of 12 months follow-up after the completion of chemoradiotherapy. With a total median follow-up of 53 months, 51% of patients who completed chemoradiotherapy had a sustained cCR the 3-year survival was 94%. A prospective Italian cooperative phase II trial (Leader Trial) assessed the impact of a transanal local excision, which provides an evaluation of TRG, on local recurrence in patients with rectal cancer who had a major clinical response after preoperative chemoradiotherapy.10 Patients with clinical MRI-based cT3 or low-lying cT2, cN0-1 disease with a major clinical response after a preoperative chemoradiotherapy underwent a full-thickness transanal local excision. Patients staged as TRG1-2 were observed, while the remaining were recommended to undergo a total mesorectal excision. The study group included 63 patients. With a median follow-up of 36 months, the estimated cumulative 3-year OS, DFS, and local DFS were 91.5% (95% CI, 75.9% to 97.2%), 91.0% (95% CI, 77.0% to 96.6%), and 96.9% (95% CI, 80.3% to 99.5%), respectively. Few studies have examined the long-term impact on the quality of life and functional outcome in patients who undergo a local excision or a nonoperative approach based on a favorable TRG.13 The benefits of conservative surgery need to be examined in the context of these clinical outcomes. There are still impediments using response to select patients for a conservative surgical approach. The challenge is identifying a surrogate noninvasive method to surgery to accurately identify patients who have achieved a favorable TRG. Current methods include endoscopy and physical exam, ultrasound, computed tomography, MRI, and positron emission tomography, either alone or in combination. Further refinements in imaging may improve the selection process. In addition, prediction models integrating imaging data with clinical variables have significantly increased the prediction for achieving a pCR.14 Another potential application of TRG would be to help select patients for postoperative adjuvant chemotherapy following preoperative chemoradiotherapy. A subgroup analysis of European Organisation for Research and Treatment of Cancer (EORTC) trial 22921 revealed that patients who responded to preoperative chemoradiotherapy had a survival benefit from postoperative chemotherapy.15 Unfortunately, TRG data were not collected in this trial. As an alternative, Valentini et al16 proposed the use of nomograms based on clinical features, pathological staging, and treatment factors to support the decision of adjuvant chemotherapy in multidisciplinary groups. There remains considerable controversy in some European countries regarding its use. An international consensus conference failed to reach a definitive recommendation.17 Although the data are impressive, the TRG score still requires surgery and it is based on pathologic evaluation. As emphasized by Fokas et al,2 it would be helpful to better understand the biologic mechanisms explaining why more locally responsive tumors are less likely to develop distant metastases. Other promising approaches include the use of molecular imaging performed during the different www.jco.org
treatment stages, integrated with clinical data and laboratory tests, possibly aimed at the development of predictive models for clinical decision support.18 In conclusion, data from Fokas et al2 offer solid evidence of the independent prognostic value of TRG following preoperative chemoradiotherapy for rectal cancer. However, the prognostic and predictive significance of TRG is still affected by uncertainties such as limited end points and the quality and heterogeneity of histological data. There are opportunities for future trials to examine the impact of TRG on specific relevant-to-the-patient goals, such as reduction of surgery extent or need for adjuvant therapies. These trials will require stratification according to pretreatment staging and sphincter function, quality of life, and the type of neoadjuvant therapy. When available, large databases may offer some guidance as to the prognostic and predictive impact of TRG. While we await these additional studies, TRG provides a valuable tool to assist in clinical decision making. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. AUTHOR CONTRIBUTIONS
Manuscript writing: All authors Final approval of manuscript: All authors REFERENCES 1. Sargent DJ, Patiyil S, Yothers G, et al: End points for colon cancer adjuvant trials: Observations and recommendations based on individual patient data from 20,898 patients enrolled onto randomized trials from the ACCENT Group. J Clin Oncol 25:4569-4574, 2007 2. Fokas E, Liersch T, Fietkau R, et al: Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: Updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:15541562, 2014 3. Bonnetain F, Bosset JF, Gerard JP, et al: What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question? Eur J Cancer 48:1781-1790, 2012 4. Valentini V, Cellini F, Barba MC, et al: Do Different Populations of Rectal Cancer Exist? in Valentini V, Schmoll HJ, van de Velde CJH (eds): Multidisciplinary Management of Rectal Cancer Questions and Answers, Berlin Heidelberg, Germany, Springer-Verlag, 2012, pp 49-55 5. Dworak O, Keilholz L, Hoffmann A: Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19-23, 1997 6. Quirke P, Williams GT. Minimum Dataset for Colorectal Cancer Histopathology Reports. London, United Kingdom, Royal College of Pathologists, 1998, pp 1-27 7. Washington MK, Berlin J, Branton P, et al: Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. Arch Pathol Lab Med 133:1539-1551, 2009 8. Vecchio FM, Valentini V, Minsky BD, et al: The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 62:752-760, 2005 9. Huebner M, Wolff BG, Smyrk TC, et al: Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg 36:675-683, 2012 10. Pucciarelli S, De Paoli A, Guerrieri M, et al: Local excision after preoperative chemoradiotherapy for rectal cancer: Results of a multicenter phase II clinical trial. Dis Colon Rectum 56:1349-1356, 2013 11. Habr-Gama A, Sabbaga J, Gama-Rodrigues J, et al: Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: Are we getting closer to anal cancer management? Dis Colon Rectum 56:11091117, 2013 12. Maas M, Beets-Tan RGH, Lambregts DMJ, et al: Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29:4633-4640, 2011 13. Coco C, Rizzo G, Mattana C, et al: Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer: Short-term morbidity and functional outcome. Surg Endosc 27:2860-2867, 2013
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Queen Mary, University of London on July 8, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 138.37.211.113
1535
Editorial
14. van Stiphout RG, Lammering G, Buijsen J, et al: Development and external validation of a predictive model for pathological complete response of rectal cancer patients including sequential PET-CT imaging. Radiother Oncol 98:126133, 2011 15. Bosset JF, Collette L, Bardet E, et al: Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114-1123, 2006 16. Valentini V, van Stiphout RGPM, Lammering G, et al: Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: Results of a phase II study. J Clin Oncol 29:3163-3172, 2011
17. van de Velde CJ, Boelens PG, Borras JM, et al: EURECCA colorectal: Multidisciplinary management—European consensus conference colon & rectum. Eur J Cancer 50:1.e1-1.e34, 2014 18. Lambin P, van Stiphout RG, Starmans MH, et al: Predicting outcomes in radiation oncology: Multifactorial decision support systems. Nat Rev Clin Oncol 10:27-40, 2013
DOI: 10.1200/JCO.2014.55.4766; published online ahead of print at www.jco.org on April 21, 2014
■ ■ ■
ASCOconnection.org—The Professional Networking Site for the Worldwide Oncology Community ● Expand your professional network and online profile ● Post your own content and news ● Respond to commentary by oncology leaders ● Create working groups on a secure site ● Connect and collaborate with colleagues ● Read exclusive articles and interviews ASCOconnection.org columnists include ASCO President Clifford Hudis, MD; ASCO President-Elect Peter Yu, MD; Past Presidents Sandra M. Swain, MD, Michael P. Link, MD, George W. Sledge Jr, MD, and Douglas W. Blayney, MD; Journal of Oncology Practice Editor-in-Chief John V. Cox, DO, MBA; Editor-in-Chief of the ASCO Educational Book, Don S. Dizon, MD; Editor-in-Chief of ASCO’s Cancer.Net Robert S. Miller, MD; and many other leaders in the oncology community. Log in with your ASCO.org member or guest account to participate.
1536
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Queen Mary, University of London on July 8, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 138.37.211.113
