The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical Outcomes in Rectal Cancer

Purpose of Review

Three-dimensional conformal radiation therapy (3DCRT) has been the standard technique in the treatment of rectal cancer. The use of new radiation treatment technologies such as intensity-modulated radiation therapy (IMRT), proton therapy (PT), stereotactic body radiation therapy (SBRT), and brachytherapy (BT) has been increasing over the past 10 years. This review will highlight the advantages and drawbacks of these techniques.

Recent Findings

IMRT, PT, SBRT, and BT achieve a higher target coverage conformity and a higher organ at risk sparing and enable dose escalation compared to 3DCRT. Some studies suggest a reduction in gastrointestinal and hematologic toxicities and an increase in the complete pathologic response rate; however, the clinical benefit of these techniques remains controversial.

Summary

The results of these new techniques seem encouraging despite conclusive data. Further trials are required to establish their role in rectal cancer.

     

体外结合腔内放射治疗局部晚期直肠癌

目的　回顾性分析体外结合腔内高剂量率放射治疗局部晚期直肠癌的近期疗效和毒副反应。方法　以体外照射和腔内高剂量后装治疗局部晚期直肠癌 ,体外照射用6 0 Co或 10MV -X线 ,三野等中心照射 ,盆腔总剂量 5 0～ 60Gy/5～ 6周 ,腔内高剂量率后装治疗与体外照射同期进行 ,按肠腔狭窄程度选用不同外径的施源器。结果　全组 64例病人经治疗肿瘤完全消失 (CR) 7例 ,肿瘤部分消退 (PR) 37例 ,1年生存率 60 9% ( 39/64)。疼痛缓解 94 7% ,止血率 10 0 %。近期毒副反应主要为腹泻 (Ⅰ～Ⅱ度 ) 82 8% ( 5 3/64)、(Ⅲ～Ⅳ度 ) 12 5 % ( 8/64)。结论　体外结合腔内放射治疗局部晚期直肠癌 ,可达到缓解症状 ,提高病人生活质量 ,延长生存时间的姑息目的     

The Selective Use of Radiation Therapy in Rectal Cancer Patients

Purpose of Review

Colorectal cancer has a high global incidence, and standard treatment employs a multimodality approach. In addition to cure, minimizing treatment-related toxicity and improving the therapeutic ratio is a common goal. The following article addresses the potential of omitting radiotherapy in select rectal cancer patients.

Recent Findings

Omission of radiotherapy in rectal cancer is analyzed in the context of historical findings, as well as more recent data describing risk stratification of stage II–III disease, surgical optimization, imaging limitations, improvement in systemic chemotherapeutic agents, and contemporary studies evaluating selective omission of radiotherapy.

Summary

A subset of rectal cancer patients exists that may be considered low to intermediate risk for locoregional recurrence. With appropriate staging, surgical technique, and possibly improved systemic therapy, it may be feasible to selectively omit radiotherapy in these patients. Current imaging limitations as well as evidence of increased locoregional recurrence following radiotherapy omission lend us to continue supporting the standard treatment of approach of neoadjuvant chemoradiation therapy followed by surgical resection until additional improvements and prospective evidence can support otherwise.

     

Adjuvant External Beam and Intraoperative Radiation Therapy in Rectal Cancer

The use of radical surgery has maximized local control, sphincter preservation, and overall survival in patients with rectal cancer. Despite the advances in surgical techniques, local recurrence still remains a problem. Following potentially curative surgery, the incidence of local recurrence inpatients with stages B2,C disease varies from 15% to 65%. There are four major approaches in which radiation therapy (RT) has been used in the adjuvant treatment of rectal cancer. These include postoperative RT ± chemotherapy, preoperative RT ± chemotherapy, both pre-and postoperative RT (sandwich technique), and intraoperative RT in conjunction with preoperative external beam RT. In patients with resectable rectal cancer, adjuvant RT has been shown to decrease the incidence of local recurrence and, in some series, may influence survival rates. In patients with locally advanced, unresectable, or recurrent rectal cancer, the use of preoperative radiation therapy, attempted surgical resection, and intraoperative RT further enhances local control.     

A Systematic Overview of Radiation Therapy Effects in Rectal Cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective studies and 17 other articles were used. A total of 131 scientific articles are included, involving 25 351 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized thus: The results after rectal cancer surgery have improved during the past decade. It is likely that local failure rates after 5 years of follow-up at hospitals adopting the TME-concept (TME=total mesorectal excision) have decreased from about 28% to 10-15%.Preoperative radiotherapy at biological effective doses above 30 Gy decreases the relative risk of a local failure by more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40% at doses that generally are higher than those used preoperatively.There is strong evidence that preoperative radiotherapy is more effective than postoperative.There is moderate evidence that preoperative radiotherapy significantly decreases the local failure rate (from 8% to 2% after 2 years) also with TME.There is strong evidence that preoperative radiotherapy improves survival (by about 10%).There is no evidence that postoperative radiotherapy improves survival.There is some indication that survival is prolonged when postoperative radiotherapy is combined with concomitant chemotherapy.Preoperative radiotherapy at adequate doses can be given with low acute toxicity. Higher, and unacceptable acute toxicity has been seen in some preoperative radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can also be given with acceptable acute toxicity.The long-term consequences of radiotherapy appear to be limited with adequate radiation techniques, although they have been less extensively studied. Longer follow-up periods are needed before firm conclusions can be drawn.Peroperative radiotherapy, preferably preoperative since it is more effective, is routinely recommended for most patients with rectal cancer since it can substantially decrease the risk of a local failure and increases survival.In a primarily non-resectable tumour, preoperative radiotherapy can cause tumour regression allowing subsequent radical surgery. This therapy is routinely indicated. Whether radiochemotherapy is more efficient than radiotherapy alone is not clear, since the results of four small randomized trials are partly conflicting.Preoperative radiotherapy, frequently combined with chemotherapy, has been used to increase the chances of sphincter-preserving surgery in low-lying tumours. The literature is inconclusive with respect to how frequently this occurs.Radiotherapy frequently produces symptom relief in patients with rectal cancer not amendable to surgery.     

低位直肠癌腔内热疗加放疗后临床病理学改变

[目的]探讨术前腔内热疗(preoperative endocavitary hyperthermia,PEH)加放疗对低位直肠癌临床病理学改变的影响。[方法]将72例低位直肠癌患者分为3组:A组30例接受术前腔内热疗加放疗,B组15例单纯放疗,C组27例未行热疗及放疗。观察3组病人治疗前和治疗后的临床表现,肿瘤大体病理改变、光镜改变及电镜改变。[结果]A组病人治疗后临床症状明显缓解;肿瘤缩小、疤痕化明显,边缘与正常组织分界清楚;光镜观察癌细胞变性、坏死、炎性细胞浸润明显;电镜观察癌细胞核破坏明显,有大量的凋亡细胞和凋亡小体。B组病人临床症状部分缓解;光镜和电镜下变化轻微;C组病人症状无改善,光镜及电镜观察无变化。[结论]PEH加放疗能明显改善低位直肠癌患者的临床症状,明显促进低位直肠癌病理改变。     

三维适形放射治疗20例复发性直肠癌

目的 探讨三维适形放射治疗对复发性直肠癌的临床疗效。方法 20例复发性直肠癌患者均采用三维适形放疗，3～4Gy／次，隔日1次，总剂量48～60Cy。结果1、2、3年生存率分别为40％（8／20），15％（3／20），5％（1／20）。结论 三维适形放射治疗可提高复发性直肠癌生存率，改善生存质量。     

Effect and Safety of Radiation Therapy Boost to Extramesorectal Lymph Nodes in Rectal Cancer

PurposeIn rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer.Methods and MaterialsWe analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups.ResultsFifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN– group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities.ConclusionsDespite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.     

Network Mapping of Molecular Biomarkers Influencing Radiation Response in Rectal Cancer

Preoperative radiotherapy (RT) plays an important role in the management of locally advanced rectal cancer (RC). Tumor regression after RT shows marked variability, and robust molecular methods are needed to help predict likely response. The aim of this study was to review the current published literature and use Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC.A systematic review of electronic bibliographic databases (Medline, Embase) was performed for original articles published between 2000 and 2015. Biomarkers were then classified according to biological function and incorporated into a hierarchical GO tree. Both significant and nonsignificant results were included in the analysis. Significance was binarized on the basis of univariate and multivariate statistics. Significance scores were calculated for each biological domain (or node), and a direct acyclic graph was generated for intuitive mapping of biological pathways and markers involved in RC radiation response.Seventy-two individual biomarkers across 74 studies were identified. On highest-order classification, molecular biomarkers falling within the domains of response to stress, cellular metabolism, and pathways inhibiting apoptosis were found to be the most influential in predicting radiosensitivity.Homogenizing biomarker data from original articles using controlled GO terminology demonstrated that cellular mechanisms of response to RT in RC—in particular the metabolic response to RT—may hold promise in developing radiotherapeutic biomarkers to help predict, and in the future modulate, radiation response.     

直肠癌根治性放疗合成计划设计的

[目的]比较适形与调强基础上合成叠加调强计划的剂量学差异.[方法]选取根治性放疗直肠癌靶区,第一程计划分别用3野适形、4野适形和5野调强对PTV给予50Gy,在第一程计划基础上合成调强计划(IMRT)给予PGTV到66Gy根治剂量.危及器官都不超量的情况下比较靶区等效生物剂量.[结果]3个叠加后计划无明显差异.不考虑第一程计划,第二程计划差异明显,PGTV 95％剂量:5野剂量为15Gy,4野剂量为13.18Gy,3野剂量为8.82Gy.[结论]直肠癌根治性放疗局部加量调强基础上的合成计划等效生物剂量更接近预期值.     

区域动脉化疗加60Co外照射治疗晚期直肠癌

１９８５年至１９９５年采用区域动脉插管化疗加６０Ｃｏ外照射的方法治疗晚期直肠癌２５例，其中术后复发１３例，单纯造瘘９例，部分切除３例。化疗每次用顺铂２０ｍｇ，５－Ｆｕ５００ｍｇ，二者交替，１２天为１周期，２周期为１个疗程，化疗后行６０Ｃｏ外照射，肿瘤量５０～６０Ｇｙ／６～７周。全组１年、２年、３年生存率分别为５３．８％、３４．６％、８．０％，而单纯造瘘组２年生存率（３８．５％）高于术后复发组（３０．８％）。结果提示，对不能切除的晚期直肠癌较适宜采用这种治疗方法，而区域动脉化疗加放疗能有效地改善晚期直肠癌的预后。     

Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy

Purpose

A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).