Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.     

Abdominosacral resection: Long-term outcome in 86 patients with locally advanced or locally recurrent rectal cancer

Aims

The purpose of this study is to evaluate the outcome of abdominosacral resections (ASR) in patients with locally advanced or recurrent rectal cancer.

Methods

From 1994 until 2012 patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) underwent a curative ASR and were enrolled in a database. The postoperative complication rates, predictive factors on oncological outcome and survival rates were registered.

Results

Seventy-two patients with LRRC (mean age 63; 44 male, 28 female) and 14 patients with LARC (mean age 65; 6 male, 8 female) underwent ASR. R0 resection was achieved in 37 patients with LRRC and 11 patients with LARC. Twenty-seven patients underwent an R1 resection (3 in the LARC group). Eight patients had an R2 resection, compared to no patients in the LARC group. In respectively 26 and 1 patients of the LRRC and LARC groups a grade 3 or 4 complication occurred and the 30-days mortality rate was respectively 3% and 7%. The 5-years overall survival was 28% and 24% respectively.

Conclusion

En bloc radical resection remains the primary goal in the treatment of dorsally located (recurrent) rectal cancer. After thorough patient selection, ASR is a safe procedure to perform, shows acceptable morbidity rates and leads to a good oncological outcome.     

Total pelvic exenteration for locally advanced and locally recurrent rectal cancer in the elderly

Background

Total pelvic exenteration (TPE) is a radical approach for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) in case of tumour invasion into the urogenitary tract. The aim of this study is to assess surgical and oncological outcomes of TPE for LARC and LRRC in elderly patients compared to younger patients.

Development of an irradiation method of intraoperative radiation therapy for curatively resected rectal cancer

Background. Intraoperative radiation therapy (IORT) has been performed to prevent local recurrence of rectal cancer only when positive margins are suspected. To further reduce local recurrence, we attempted to develop a new IORT irradiation method in which electron beam irradiation is administered as uniformly as possible to the intrapelvic dissection surfaces. Methods. Low anterior resection and abdominoperineal resection were performed in one male and one female cadaver. Electron beam irradiation was administered by four different methods, and absorbed doses were measured at 15 sites within the pelvis. We also attempted to measure absorbed doses at nine sites within the pelvis in 14 patients treated with IORT. Results. The cadaver study revealed low absorbed doses in the lateral walls of the pelvis when a single irradiation was delivered from the anterior. When the lateral walls of the pelvis were irradiated twice, once each time on the right and left, the absorbed doses were low in the central pelvis and presacrum. Relatively high absorbed doses were achieved in all of these areas by a technique that combined these two methods. Adequate absorbed doses were not achieved by a single irradiation administered from the perineum. Conclusion. This study suggests that electron beam irradiation administered three times to the dissected surfaces in the pelvis after resection of rectal cancer (i.e., to the central pelvis and presacrum from the anterior, and to the left and right lateral walls of the pelvis) is the most suitable method for achieving adequate absorbed doses. Received: May 6, 1998 / Accepted: December 15, 1998     

Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: A systematic review and meta-analysis

PurposeWe conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60 Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval.Methods and materialsPubMed, EMBASE and Cochrane libraries were searched with the terms ‘radiotherapy’, ‘boost’ and ‘rectal cancer’ and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier.ResultsThe search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8–24.5%), with low heterogeneity (I² 0.0%, 95% CI 0.00–84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4–18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2–95.3%).ConclusionDose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.     

TAI联合放射治疗晚期直肠癌的临床研究

目的探讨经直肠下动脉介入化疗(TAI)方案联合放射治疗晚期直肠癌的疗效及毒副反应。方法回顾分析68例晚期直肠癌的随访资料,根据治疗方法不同分为TAI联合放射治疗组和单纯放疗组,分析肿瘤的缓解率、患者的生存率及毒副反应。结果TAI方案联合放疗组在肿瘤的消失、缩小方面优于单纯放疗组,两者差异有显著意义(P<0.05)。TAI组联合放疗组1、2、3年的生存率明显高于单纯放疗组,两者有显著性差异(P<0.05);5年生存率相近,但TAI组联合放疗组较单纯放疗组消化道I~II度毒副反应发生率明显增加,差异有显著性意义(P<0.05)。结论TAI方案联合放射治疗能提高局控率,降低复发率,减少局部淋巴和远处转移率,有效提高长期生存率,且并发症发生率较低,是一种简单、安全、较理想的中晚期直肠癌的治疗方案,有临床推广价值。     

三维适形放疗联合化疗治疗局部晚期和术后复发性直肠癌

目的：探讨局部晚期和术后复发性直肠癌三维适形放射治疗（3D—CR）联合化疗的临床疗效。方法：30例局部晚期和术后复发性直肠癌采用常规放射治疗至40Gy，再予后程适形放疗加化疗。适形放疗25Gy-30Gy，肿瘤总量65Gy-70Gy；化疗采用奥沙利铂130mg／m^2，d1，亚叶酸钙100mg／m^2，d1-5,5-氟脲嘧啶500mg／m^2，d1-5。结果：患者有效率为90％；12、24、36月生存率分别为83．3％，60％，40％；12、24、36月局部控制率分别为90％，83．3％，56．7％。胃肠道反应、骨髓抑制、放射性直肠炎、放射性膀胱炎为主要副反应，多为1—2级。结论：三维适形放疗联合化疗可提高局部晚期和术后复发性直肠癌的控制率和生存率。     

Role of radiation therapy in neoadjuvant era in patients with locally advanced rectal cancer

Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.     

Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreas cancer

Purpose

To retrospectively compare the efficacy and toxicity of full-dose gemcitabine based chemoradiotherapy (GemRT) versus 5-fluorouracil (5-FU) based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC).

Methods

From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n = 38) or GemRT (n = 55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000 mg/m² weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact.

Results

Patient characteristics were not significantly different between treatment groups. The overall survival (OS) was significantly better for GemRT compared to 5FURT (median 12.5 months versus 10.2 months; 51% versus 34% at 1 year; 12% versus 0% at 3 years; 7% versus 0% at 5 years, respectively; all P = 0.04). The OS benefit of GemRT was maintained on subset analysis without concurrent erlotinib or with sequential gemcitabine (all P < 0.05). The rates of distant metastasis, subsequent hospitalization, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups.

Conclusions

GemRT was associated with an improved OS compared to standard 5FURT. This approach yielded long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity.     

Long-term results after intraoperative radiation therapy for gastric cancer

PURPOSE: We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. METHODS AND MATERIALS: From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6-15 MeV; IORT-positive [IORT(+)] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT(-)] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I (n = 31), II (n = 11), III (n = 14), and IV (n = 5). RESULTS: Mean follow-up was 4.8 years in the IORT(+) group and 5.0 years in the IORT(-) group. The overall 5-year patient survival rate was 58% in the IORT(+) group vs. 59% in the IORT(-) group (p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT(+) vs. IORT(-) group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT(+) vs. IORT(-) group. Total surgical complications were more common in the IORT(+) than IORT(-) group (44.3% vs. 19.7%; p < 0.05). The locoregional tumor recurrence rate was 9.8% in the IORT(+) group. CONCLUSIONS: Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.     

Evaluation of the efficacy of modified De Gramont and modified FOLFOX4 regimens for adjuvant therapy of locally advanced rectal cancer

Objective: To evaluate the efficacy of modified De Gramont (mDG) and FOLFOX4 (mFOLFOX4) regimens in patients with locally advanced rectal cancer (LARC). Methods: Patients that received adjuvant chemotherapy (CT) for the treatment of LARC (stage II and III) were retrospectively evaluated. Results: A total of 231 patients were examined. Median age was 58 (range, 18-83) and, of these patients, 36 (15.6%) had stage II and 195 (84.4%) had stage III disease. While the patients with stage II disease received only mDG regimen (36, 100.0%), of the patients with stage III disease, 71 (36.5%) received mDG and 124 (63.5%) received mFOLFOX4 regimen. Patients with stage III disease showed recurrences more often, but this difference was not statistically significant. Similarly, for the patients with stage III disease, there was no statistically significant relation between the adjuvant CT regimen received and the rate of recurrence. In patients with stage II disease, who received mDG, median DFS was 101 months and median OS was 106 months. For the patients with stage III disease, the patients that received mDG showed a median DFS of 78 months and a median OS of 96 months, while the patients that received mFOLFOX4 had a median DFS of 51 months and a median OS of 78 months. Although, for the patients with stage III disease, there are major differences between the two different regimens of CT in terms of DFS and OS, this difference was not statistically significant.When the results were evaluated from the perspective of toxicity, the patients that received mFOLFOX4 showed more toxicity. Neurotoxicity, which was seen in the patients that were given mFOLFOX4, was the most prominent toxicity. Conclusions: mDG and mFOLFOX4 regimens are applicable regimens as adjuvant CT for the treatment of LARC.     

Patterns of local recurrence in locally advanced rectal cancer after intra-operative radiotherapy containing multimodality treatment

Background and purpose

The purpose of this study is to analyze the patterns of local recurrence (LR) after intra-operative radiotherapy (IORT) containing multimodality treatment of locally advanced rectal carcinoma (LARC).

Methods and materials

Two hundred and ninety patients with LARC who underwent multimodality treatment between 1994 and 2006 were studied. For patients who developed LR, the subsite was classified into presacral, postero-lateral, lateral, anterior, anastomotic or perineal. Patient and treatment characteristics were related to subsite of LR.

Results

After 5 years, 34 patients (13.2%) developed LR. The most prominent subsite of LR was the presacral subsite. 47% of the local recurrences occurred outside the IORT field. Most recurrences developed when IORT was given dorsally, while least occurred when IORT was given ventrally. Especially after dorsal IORT a high amount of infield recurrences were observed (6 of 8; 75%). In multi-variate analysis tumor distance of more than 5 cm from the anal verge and a positive circumferential margin were associated with presacral local recurrence.

Conclusions

Multimodality treatment is effective in the prevention of local recurrence in LARC. IORT application to the area most at risk is feasible and seems effective in the prevention of local recurrence. Dorsal tumor location results in unfavourable oncologic results.     

Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer

Introduction

Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands.

Management of locally advanced carcinoma of the breast by primary radiation therapy

We performed a retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54%, 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced-breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.     

全程新辅助治疗模式用于局部进展期直肠癌治疗的研究进展

大肠癌在全球范围内是一种发病率较高的实体性肿瘤,直肠癌手术难度大、并发症发生率高、局部复发率比较高,尤其是局部进展期直肠癌(locally rectal cancer,LAＲC)治疗效果较差,随着多学科综合治疗理念在直癌中的应用,特别是新辅助放化疗应用于局部进展期直肠癌的治疗,患者的治疗效果得到改善,局部进展期直肠癌领域是目前研究的重点和热点之一,本文对目前最新的2018年美国NCCN直肠癌肿瘤学临床实践指南中局部进展期直肠癌新辅助同步放化疗、新辅助短程放疗、全程新辅助治疗(total neoadjuvant therapy,TNT)的模式进行综述。     

同期放化疗治疗局部晚期不可手术的直肠癌近期疗效观察

目的：观察同期放化疗治疗局部晚期不可手术的直肠癌患者的近期疗效及耐受性。方法：３８例经病理证实的局部晚期或局部 区域复发的直肠癌患者接受全盆腔三维适形放疗ＤＴ４６～５０Ｇｙ／２３～２５ｆ,后缩野至肿瘤区继续推量至ＤＴ６４～６６Ｇｙ／３２～３３ｆ,同期接受奥沙利铂１３０ｍｇ／ｍ^２ｄ_１,氟尿嘧啶３５０ｍｇ／ｍ^２ｄ_１～ｄ_５,甲酰四氢叶酸２００ｍｇ／ｍ^２ｄ_１～ｄ_５,４周为１周期,共２个周期。结果：获ＣＲ７例（１９.４％）,ＰＲ１６例（４４.４％）,ＳＤ６例（１６.７％）,ＰＤ７例（１９.４％）,总有效率（ＣＲ＋ＰＲ）为６３.９％;疼痛症状缓解率为１００％;全身状况好转率７２.２％;中位生存时间为２２个月,１年和２年总生存率分别为６７.７％和２１.３％。治疗相关的毒副反应以中性粒细胞减少、腹泻、恶心呕吐以及周围神经毒性反应为主,其３级毒副反应的发生率分别为１９.４％、１６.７％、１３.９％和１１.１％,均无３级以上毒副反应发生。结论：以奥沙利铂为基础的化疗同期联合放疗对局部晚期不可手术直肠癌患者具有较好的姑息治疗作用,其治疗依从性高,治疗相关毒性可以接受,值得临床进一步推广。     

局部晚期喉癌3DCRT与IMRT放疗计划的剂量学对比

目的 利用ECLIPSE计划系统对局部晚期喉癌适形放疗(3DCRT)和逆向调强适形放疗(IMRT)计划作剂量学比较,评估不同照射方法的优缺点。方法 选择6例病理证实的局部晚期喉癌患者,用ECLIPSE对每例患者分别作出3DCRT和IMRT计划。根据靶区V95%、D5%、D95%、靶区最大值、最小值及平均值和正常组织受量D50、D33、D5、Dmax和Dmean来比较这两种计划剂量学的差异。结果 两种不同计划中的靶区分布中,GTV和GTVnd差别不大,但对于亚临床区CTV和某些正常组织有统计学差异。结论 对局部晚期喉癌原发灶及阳性淋巴结,3DCRT和IMRT计划均有较好覆盖。但在亚临床病灶方面,IMRT比3DCRT包含靶区更好一些,且IMRT减少了腮腺正常组织的照射剂量。