• Boost
• Dose escalation
• MR-Linac
• Rectal cancer

• Aged
• Humans
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Prospective Studies
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted
• Radiotherapy, Intensity-Modulated
• Rectal Neoplasms/diagnostic imaging
• Rectal Neoplasms/radiotherapy

• Biological therapy
• Colorectal cancer
• Complete pathological response
• Neo-adjuvant therapy
• Rectal cancer

The role of radiation therapy in the treatment of (colo)-rectal cancer has changed dramatically over the past decades. Introduced with the aim of reducing the high rates of local recurrences after conventional surgery, major developments in imaging, surgical technique, systemic therapy and radiation delivery have now created a much more complex environment leading to a more personalized approach. Functional aspects including reduction of acute or late treatment-related side effects, sphincter or even organ-preservation and the unsolved problem of still high distant failure rates have become more important while local recurrence rates can be kept low in the vast majority of patients. This review summarizes the actual role of radiation therapy in different subgroups of patients with rectal cancer, including the current standard approach in different subgroups as well as recent developments focusing on neoadjuvant treatment intensification and/or non-operative treatment approaches aiming at organ-preservation.

• Chemoradiation
• Rectal cancer
• Review

• Inverse planning
• locally advanced rectal cancer
• meta-analysis
• pathological complete response
• radiotherapy boost

• IMRT
• preoperative radiotherapy
• rectal cancer
• surgery
• three-dimensional conformal radiotherapy

• National Natural Science Foundation of China

• Rectal cancer
• adaptive dose escalation
• radiotherapy
• rectal organ preservation

Pathologic complete response to neoadjuvant chemoradiation therapy (CRT) is associated with improved outcomes for patients with locally advanced rectal cancer (LARC). Increased response rates have been reported with higher radiation doses, but these studies often lack long-term outcome and/or toxicity data. We conducted a case-control analysis of patients with LARC who underwent definitive CRT to determine the efficacy and safety of intensified treatment with a concomitant boost (CB) approach.

From 1995 to 2003, a phase 2 protocol examined CRT with 5-fluorouracil and CB radiation therapy (52.5 Gy in 5 weeks) for patients with LARC. Seventy-six protocol patients were matched (case-control approach) for surgery type, tumor (T) stage, and clinical nodal (N) stage with patients who received standard dose (SD) CRT (5-fluorouracil, 45 Gy). A chart review was performed. McNemar's test and Kaplan-Meier analyses were used for statistical analysis.

The SD and CB groups did not differ in tumor circumferential involvement and length, but the tumors of CB patients were closer to the anal verge (4.7 vs 5.7 cm; P = .02). Although tumor downstaging was higher in the CB cohort (76% vs 51%; P < .01), pathologic complete response rates did not differ (CB, 17.1% vs SD, 15.8%, P = 1.00). The incidence of grade ≥3 radiation-related toxicities was low and similar in both groups (CB, 10% vs SD, 3%, P = .22). Postoperative (anastomotic leak, wound complications/abscess, bleeding) and late (small bowel obstruction, stricture) complication rates did not differ between the groups (P > .05). The median follow-up was 11.9 years. The 5-year local control rates were higher for CB (100.0%) compared with SD (90.0%) patients (P = .01). CB patients had higher rates of 10-year progression-free survival (71.9% vs 57.6%, P < .01) and overall survival (71.6% vs 62.4%, P = .01) compared with SD patients.

CRT dose escalation for patients with LARC is safe and effective. The improved T-downstaging and local control observed in CB patients should encourage further dose escalation studies.

• Oncologic outcomes
• Preoperative chemoradiotherapy
• S-1 plus Irinotecan
• T4 lower rectal cancer

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Camptothecin/administration & dosage
• Camptothecin/analogs & derivatives
• Chemoradiotherapy, Adjuvant
• Digestive System Surgical Procedures
• Drug Combinations
• Female
• Follow-Up Studies
• Humans
• Irinotecan
• Male
• Middle Aged
• Neoplasm Staging
• Oxonic Acid/administration & dosage
• Preoperative Period
• Rectal Neoplasms/mortality
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Survival Rate
• Tegafur/administration & dosage
• Time Factors
• Treatment Outcome

• Boost radiation
• Locally advanced rectal cancer
• Meta-analysis
• Pathologic complete response
• Systematic review

• chemoradiotherapy
• radiotherapy
• rectal cancer
• surgery
• time interval
• tumor regression

In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a loco-regional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy × 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy × 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging.

• Chemotherapy
• Chemoradiotherapy
• Local control
• Multidisciplinary
• Organ preservation
• Radiotherapy
• Randomized trials
• Rectal cancer

• Chemoradiotherapy, Adjuvant
• Humans
• Neoadjuvant Therapy/adverse effects
• Neoplasm Recurrence, Local/prevention & control
• Neoplasm Staging
• Patient Selection
• Predictive Value of Tests
• Radiotherapy, Adjuvant
• Rectal Neoplasms/pathology
• Rectal Neoplasms/radiotherapy
• Rectal Neoplasms/surgery
• Risk Factors
• Treatment Outcome