Predictive factors in locally advanced rectal cancer treated with preoperative hyperfractionated and accelerated radiotherapy

Abstract

Colorectal cancer is a significant cause of morbidity and mortality in Western populations. More than 1/3 of cases occur in the rectum, with an outcome after surgery less favorable than for colon cancer, as reflected in local recurrence rates of 20% to 50% after traditional surgical treatment. 1 Moreover, rectal cancer is characterized by a higher incidence of regional lymph nodes and distant metastases. Preoperative radiotherapy has been shown to reduce local failure rates and to improve overall survival. 1-4 However, results of different clinicopathologic studies are sometimes contradictory, which might be related to the heterogeneity in radiation treatment-related factors and clinical stages. Absence of a standardized method for pathologic analysis might be another source of discrepancies.We have adopted a treatment schedule that aims to accelerate the treatment to counter tumor proliferation during treatment and to reduce the risk of late complications by hyperfractionation (ie, reducing the dose per fraction). This hyperfractionated accelerated radiotherapy (HART) schedule was tested in locally advanced rectal cancer, that is, T3 and T4 and any N, or any T but Nϩ, rectal cancers. 5,6 We demonstrated that preoperative HART is feasible and is associated with a lower toxicity than postoperative radiotherapy. 5 Based on this initial experience, a phase II trial was initiated.Whether or not classical predictive factors of survival for colorectal cancer are still important after neoadjuvant therapy is a question frequently asked by pathologists, and only sporadic studies with a systematic pathologic approach try to answer it. In this study we attempted to correlate response to radiotherapy with pathologic variables and to determine which pathologic variables, including histological assessment of response to radiotherapy, correlated with disease outcome. PATIENTS AND METHODSThe study group comprised 104 patients with locally advanced rectal cancer recruited in a phase II trial (93-01) on preoperative HART between 1992 and 1998. Assessment of the clinical stage was based on digital rectal examination, completed by both rectal ultrasonography and computed tomography (CT) scan. During this time period, all patients were eligible if they presented at preoperative work-up with cT3 or cT4, regardless of the N stage. The HART protocol was reviewed by the local ethics committee. All patients gave informed consent. Patients with coexisting cancer or chronic

Circumferential resection margin as a prognostic factor after rectal cancer surgery: A large population‐based retrospective study

“…However, some researchers argued that CRM <2 mm was associated with a negative prognosis 18, 19, 20, 21, 22. A CRM clearance of >5 mm and 0.4 mm was proposed by Kelly et al1 in 2009 and Beaufrère et al23 in 2017, respectively.…”

“…The criterion to define a positive CRM remains unclear. However, some researchers believed that CRM within 2 mm was associated with a negative prognosis 18, 19, 20, 21, 22. In addition, Kelly et al1 argued that a CRM clearance >5 mm should be achieved to optimize curative treatment.…”

Mucinous carcinoma of the rectum: a distinct clinicopathological entity

“…As part of the analysis, they found that in addition to there being an increased proportion of mucinous tumours found following neo-adjuvant treatment, this was further enhanced in the group with chemo-and radiotherapy than just pre-operative radiotherapy alone [36]. This phenomenon is not fully understood; however, one explanation offered by the College of American Pathologists is that mucinous change is a feature of response to pre-operative treatment [33].…”

“…For example, they are identified as mucinous on biopsy and/or MRI as well as on the surgical resection specimen. These tumours appear to have the worst prognosis and increased risk of local recurrence [33,34]. The documentation of the extent of residual cellular mucin is important since the risk of tumour spillage from such mucin pools will increase the risk of local recurrence.…”

Usefulness of two independent histopathological classifications of tumor regression in patients with rectal cancer submitted to hyperfractionated pre-operative radiotherapy

“…The value of ypT parameter equal or higher than uT indicates lack of tumor regression [11,14,[17][18][19][20][21] . This parameter may also be applied to the regression of metastatic regional lymph nodes in rectal cancer, "N-downstaging" [17,20,[22][23][24][25][26] .…”