Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab,capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer

BackgroundTo evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer.Patients and methodsAdults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m², day 1) intravenously and capecitabine (1000 mg/m² twice daily orally, days 1–14) for up to six cycles. Surgery was carried out 6–8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated.ResultsOf 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%–90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%–84.5%). Toxic effects were tolerable. No treatment-related deaths occurred.ConclusionsRadical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab–capecitabine–oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.     

Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

BACKGROUNDFor locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIMTo compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODSIn a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTSCompared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05).CONCLUSIONCompared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score.     

Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II–III rectal cancer

Introduction

A prospective phase II study was conducted to assess the clinical activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for neoadjuvant therapy of stages II?CIII rectal cancer.

Materials and methods

Patients with histologically confirmed stages II?CIII (T3?CT4 and/or N+) resectable rectal adenocarcinoma were eligible. Capecitabine was administered at 825?mg/m² twice daily for 5?days/week and oxaliplatin at 50?mg/m² on day 1 weekly for 5?weeks starting the first day of RT (before RT). RT consisted of a total dose of 45?Gy delivered in 25 fractions of 1.8?Gy, 5?days per week, for 5?weeks.

Results

A total of 46 patients were included (35 male, 10 female, median age 62?years). TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected nodal involvement. The intended chemoradiation treatment was completed in 94?% patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4 patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients, Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2. Forty-two patients underwent surgery (complete resection 95?%, sphincter-saving operation 55?%). The overall pathologic response rate was 83?%, with a pathologic complete response (pCR) rate of 11.9?% (95?% CI 4.0?C25.6).

Conclusions

The pCR rate observed with oxaliplatin plus capecitabine and RT did not reach the pre-specified criteria of efficacy in this trial, which is in line with recent results of randomized phase III trials.     

Phase II and gene expression analysis trial of neoadjuvant capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced rectal cancer: Hoosier Oncology Group GI03-53

Purpose

We designed this study in locally advanced rectal cancer to determine the pathological response, toxicity, and disease-free survival (DFS) with induction capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy (CRT) and analyze the gene expression of enzymes involved in the metabolism of capecitabine and irinotecan for associations with response and toxicity.

Methods

Patients with T3/T4 or node positive rectal cancer were treated with capecitabine 1,000?mg/m² twice daily (BID) days 1?C14, and irinotecan 200?mg/m² on day 1 every 21?days for 2 cycles, followed by capecitabine 825?mg/m² BID days 1?C5 per week with concurrent radiotherapy 50.4?Gy in 28 fractions. Surgical resection occured a median of 7.4?weeks after CRT. Gene expression levels or sequencing were used to analyze carboxylesterase-converting enzymes (CES1, CES2), thymidylate synthase (TS), thymidine phosphorylase (TP), dehydropyrimidine dehydrogenase (DPD), topoisomerase I (TOPO I), and uridine-diphosphate (UDP) glucuronosyl transferase 1A1 in pre- and post-treatment tumor and normal tissue samples.

Results

Twenty-two patients were enrolled, and 18 completed neoadjuvant therapy and underwent R0 resection. Two patients with UGT1A1 7/7 had grade 3 and 4 neutropenic fever and sepsis. Pathological complete response (pCR) occurred in 6 of 18 patients (33?%) and 10 (56?%) had tumor and/or nodal downstaging. The 3-year DFS was 75.5?% (95?% CI, 39.7?C91.8?%). Locoregional control rate was 100?%. We observed higher TP gene expression in pCR patients, but no correlations with toxicity.

Conclusions

This neoadjuvant regimen was safe and demonstrated significant antitumor activity. High TP tumor gene expression was associated with obtaining pCR.     

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone

Purpose: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer.

Methods: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n?=?61) or without (n?=?45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group). Target temperature was 40.5°C for at least 60?min. Total mesorectal excision was performed routinely.

Results: pCR was seen in 6.7% of patients in the RCT group and 16.4% in the HRCT group. Patients who received at least four hyperthermia treatments (n?=?40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 patients (p?=?0.043). Rates of sphincter-sparing surgery were similar in both groups with 64% in the RCT group and 66% in HRCT. When considering only low-lying tumours located within 8?cm of the anal verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the HRCT group compared with 35% in the RCT group (p?=?0.077).

Conclusion: The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.     

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study

Purpose

The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

Methods

Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m² per day; 60 % dose at 8:00 AM and 40 % dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity.

Results

In 17 patients (20 %), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5 %), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5 %) subjects, and grade I or II cystitis in six (6.9 %). Only three patients (3.3 %) developed hand and foot syndrome (both grade I–II). There were no grade IV toxicities.

Conclusions

Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer.     

Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study

Background.

Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer.

Patients and Methods.

Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m² twice daily on days 1–15). Surgery was scheduled for 6–8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR).

Results.

Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%–51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention.

Conclusions.

Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications.     

Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer

BACKGROUNDPatients with clinical T4 colorectal cancer (CRC) have a poor prognosis because of compromised surgical margins. Neoadjuvant therapy may be effective in downstaging tumors, thereby rendering possible radical resection with clear margins. AIMTo evaluate tumor downsizing and resection with clear margins in T4 CRC patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery.METHODSThis study retrospectively included 86 eligible patients with clinical T4 CRC who underwent neoadjuvant concurrent chemoradiotherapy followed by radical resection. Neoadjuvant therapy consisted of radiation therapy at a dose of 45-50.4 Gy and chemotherapy agents, either FOLFOX or capecitabine. A circumferential resection margin (CRM) of < 1 mm was considered to be a positive margin. We defined pathological complete response (pCR) as the absence of any malignant cells in a specimen, including the primary tumor and lymph nodes. A multivariate logistic regression model was used to identify independent predictive factors for pCR.RESULTSFor 86 patients who underwent neoadjuvant chemoradiotherapy and surgery, the rate of pCR was 14%, and the R0 resection rate was 91.9%. Of the 61 patients with rectal cancer, 7 (11.5%) achieved pCR and 5 (8.2%) had positive CRMs. Of the 25 patients with colon cancer, 5 (20%) achieved pCR and 2 (8%) had positive CRMs. We observed that the FOLFOX regimen was an independent predictor of pCR (P = 0.046). After a median follow-up of 47 mo, the estimated 5-year overall survival (OS) and disease-free survival (DFS) rates were 70.8% and 61.4%, respectively. Multivariate analysis revealed that a tumor with a negative resection margin was associated with improved DFS (P = 0.014) and OS (P = 0.001). Patients who achieved pCR exhibited longer DFS (P = 0.042) and OS (P = 0.003) than those who did not.CONCLUSIONNeoadjuvant concurrent chemoradiotherapy engenders favorable pCR and R0 resection rates among patients with T4 CRC. The R0 resection rate and pCR are independent prognostic factors for patients with T4 CRC.     

Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.     

Simultaneous radiotherapy and superficial hyperthermia for high-risk breast carcinoma: A randomised comparison of treatment sequelae in heated versus non-heated sectors of the chest wall hyperthermia

Purpose: In vitro data demonstrate that heat-induced radiosensitisation is maximised if hyperthermia and radiotherapy are given simultaneously, with the radiation fraction delivered midway through a hyperthermia session, rather than sequentially. The long-term normal tissue toxicity of full-dose simultaneous thermoradiotherapy is unknown.

Materials and methods: Patients with locally advanced breast cancer (T3, T4 or more than three involved nodes or local recurrence), no prior radiotherapy, received between four and eight sessions of simultaneous thermoradiotherapy. Hyperthermia always included the primary tumour site. In addition an electively heated sector (EHS) was included. The EHS was randomised to either medial or lateral to the tumour site, with the other side an irradiated but unheated control. As per our usual practice, patients received surgery and/or chemotherapy prior to radiotherapy. Radiation doses were 46–50?Gy followed by a boost of ≤16?Gy at 1.8–2?Gy per fraction. EHS and control sectors received the same dose.

Results: A total of 57 evaluable cases with average follow-up of 79 months experienced two local and two nodal recurrences. There was no significant difference in ≥grade 2 toxicity for heated versus control sectors (LR χ^2?=?0.78, p?=?0.38) with no relationship between number of hyperthermia sessions and toxicity (LR χ^2?=?2.90, p?=?0.09).

Conclusions: Simultaneous full-dose thermoradiotherapy for breast cancer is feasible and well tolerated, with no significant difference in late toxicity between electively heated and unheated control sectors. All patients had hyperthermia to the primary tumour site with excellent local control.     

26例低位局部进展期直肠癌术前加量IMRT临床观察

目的 探讨低位直肠癌患者行术前同期加量IMRT联合卡培他滨化疗方案的可行性及治疗效果。方法 选取2015-2016年301医院26例局部晚期直肠癌患者,肠镜下肿瘤下缘距肛缘5 cm内。放疗剂量分割模式:直肠肿瘤及转移淋巴结为58.75 Gy分25次(2.35 Gy/次),盆腔淋巴引流区为50 Gy分25次,同步卡培他滨化疗(825 mg/m²,2 次/d,5天/周)5周。同步放化疗结束后休息1周,继续辅以1个周期卡培他滨化疗(1250 mg/m²,2 次/d,连续14 d)。同步放化疗结束后6~8周行直肠TME。研究主要终点为获得ypCR及保肛手术率,次要终点为急性放化疗反应、TN降期率及术后并发症。结果 26例患者均完成新辅助放化疗,其中25例患者已行手术治疗,1例患者因肛周水肿无法手术。术后ypCR率达32%(8/25),保肛手术率为60%(15/25);TN总降期率为92%(23/25),R0切除率为100%。放化疗期间24例患者发生1、2级不良反应,2例患者发生3级放射性皮炎,未见≥4级急性不良反应。术后输尿管损伤1例,肠梗阻1例。结论 低位直肠癌患者行术前同期加量IMRT联合卡培他滨化疗方案安全可行,ypCR、R0切除率及保肛手术率达到了预期效果,长期生存是否获益有待今后进一步研究。临床试验注册 中国临床试验注册中心,注册号:ChiCTR-ONC-12002387。     

The efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer

BackgroundThis study aimed to evaluate efficacy and adverse effects of different radiotherapy (RT) doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer.MethodsFifty-nine patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy in hospital between January 2015 and May 2017 were enrolled in retrospective analysis. The patients were divided into the 56-Gy group and the 50-Gy group. The concurrent chemotherapy regimen was based on capecitabine. All patients received one cycle of oxaliplatin combined with capecitabine induction chemotherapy. All patients completed neoadjuvant chemoradiotherapy and received radical surgery.ResultsOf the patients in this study, 29 patients and 30 patients received a radiation dose of 56- and 50-Gy, respectively. All clinical characteristics were matched between the two groups. All patients received surgery 6 to 8 weeks after completing RT. The therapeutical effective rate in the 56-Gy group was 93.10% (27/29), compared with 66.67% in the 50-Gy group (20/30); the difference between the two groups was statistically significant (χ²=6.36, P=0.01). The pathological complete remission (pCR) rate in the 56-Gy group (37.93%, 11/29) was statistically significantly higher than that in the 50-Gy group (13.33%, 4/30) (χ²=4.71, P=0.030). The anal preservation rate in the 56-Gy group (65.5%, 19/29) was statistically significantly higher than that in the 50-Gy group (33.33%, 10/30) (χ²=6.11, P=0.01). The 56-Gy group had a local recurrence rate of 0% (0/29) and a distant metastasis rate of 10.34% (3/29), while the 50-Gy group had a local recurrence rate of 6.67% (2/30) and a distant metastasis rate of 16.67% (5/30); no significant difference existed between the two groups (χ²=2.00, 0.50, P=0.16, 0.48). The incidence of adverse reactions (gastrointestinal reactions, bone marrow suppression, and perianal skin reactions) in the 56-Gy group was not significantly different from that in the 50-Gy group (P>0.05).ConclusionsIncreasing the radiation dose can significantly improve the anal preservation and pCR rates of patients with locally advanced rectal cancer, thus improving their life quality. Moreover, it does not increase the rates of recurrence or adverse reactions. Our findings have certain clinical significance, but further prospective study is needed.     

局部中晚期直肠癌术前新辅助同期加量IMRT联合术前化疗的Ⅱ期临床研究

目的 观察评估局部中晚期直肠癌术前SIB-IMRT联合1周期卡培他滨诱导化疗联合全直肠系膜切除术治疗方案的可行性、安全性及疗效。方法 2015-2016年入组37例局部中晚期直肠癌患者接受术前放疗,直肠病变及阳性淋巴结给予58.75 Gy分25次,盆腔淋巴引流区给予50.00 Gy分25次,同步卡培他滨化疗。同步放化疗结束后休息1周继续行1周期卡培他滨诱导化疗。同步放化疗结束后6~8周接受直肠癌根治术。研究主要终点为pCR,次要终点为TN降期率、保肛手术率、不良反应等。结果 37例患者顺利完成术前同步放化疗,32例行手术治疗,4例因症状缓解拒绝手术,1例患者因肛周水肿手术延迟。pCR率为34%(11/32),TN降期率为91%(29/32),R₀切除率为100%,保肛手术率为75%(24/32)。放化疗期间大部分为1、2级急性不良反应,3、4级不良反应共3例。术后并发症为输尿管损伤(1例)和肠梗阻(1例),围手术期内未见死亡。结论 局部中晚期直肠癌行术前SIB-IMRT联合1周期卡培他滨术前化疗及全直肠系膜切除术方案的初步结果表明其近期疗效好、安全可行、急性不良反应轻。     

ShorTrip Trial: A Prospective,Multicentric Phase II Single-Arm Trial of Short-Course Radiotherapy Followed by Intensified Consolidation Chemotherapy With the Triplet FOLFOXIRI as Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

BackgroundIn patients with locally advanced rectal cancer (LARC) treated with preoperative (chemo) radiotherapy and surgery, adjuvant chemotherapy is poorly feasible and its benefit is questionable. In the last years, several total neoadjuvant treatment (TNT) strategies, moving the adjuvant chemotherapy to the neoadjuvant setting, have been investigated with the aim of improving compliance to systemic chemotherapy, treating micrometastases earlier and then reducing distant recurrence.Patients and MethodsShorTrip (NTC05253846) is a prospective, multicentre, single-arm phase II trial where 63 patients with LARC will be treated with short-course radiotherapy followed by intensified consolidation chemotherapy with FOLFOXIRI regimen and surgery. Primary endpoint is pCR. Among the first 11 patients who started consolidation chemotherapy, a preliminary safety analysis showed a high rate of grade 3 to 4 neutropenia (N = 7, 64%) during the first cycle of FOLFOXIRI. Therefore, the protocol has been emended with the recommendation to omit irinotecan during the first cycle of consolidation chemotherapy. After amendment, in a subsequent safety analysis focused on the first 9 patients treated with FOLFOX as first cycle and then with FOLFOXIRI, grade 3 to 4 neutropenia was reported in only one case during the second cycle.Aim of the studyThe aim of this study is to assess the safety and activity of a TNT strategy including SCRT, intensified consolidation treatment with FOLFOXIRI and delayed surgery. After protocol amendment, the treatment seems feasible without safety concern. Results are expected at the end of 2024.     

直肠癌新辅助放化疗后病理完全缓解的临床因素分析

目的 评估影响直肠癌新辅助放化疗后pCR的临床因素。方法 回顾分析2009—2012年间接受新辅助放化疗随后行根治性手术的116例直肠癌患者临床资料。所有患者术前接受盆腔调强放疗50 Gy分25次,同期氟尿嘧啶为基础化疗,完成治疗休息4~8周后行根治性手术。应用 Logistic法分析影响pCR和非pCR的临床因素。结果 共20例患者经新辅助放化疗后达pCR,pCR率为17.2%。单因素分析表明肿瘤侵犯直肠管腔周径范围达75%以上(全周肿瘤)、治疗前血清CEA水平、T分期、N分期、肛缘距离、分化程度、肿瘤最大直径与直肠癌新辅助放化疗后肿瘤pCR水平相关。多因素分析结果显示全周肿瘤、治疗前血清CEA水平和T分期是影响放化疗后肿瘤pCR预测因素。结论 非全周肿瘤、低CEA水平和早T分期等治疗前临床因素可能是获得pCR的重要决定因素。     

Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: A phase II multi-institutional clinical trial (KROG 11-02)

Purpose

The aim of this study was to evaluate the efficacy and safety of a two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer.

Methods and materials

Eighty patients with rectal cancer located in the mid to low rectum, staged cT3-4N0-2M0, were prospectively enrolled. They underwent preoperative chemoradiotherapy and delayed surgery 6–8 weeks after the completion of radiation therapy. A radiation dose of 33 Gy in 10 fractions was delivered to the pelvis for 2 weeks. One cycle of oral capecitabine was administered at a dose of 1650 mg/m²/day during radiotherapy. Tumor response and toxicity were the study endpoints. This study was registered at ClinicalTrials.gov (number, NCT01431599).

Results

All included patients underwent total mesorectal excisions including 12 cases of robot assisted surgery and 50 cases of laparoscopic surgery. Of the 80 patients, 27 (33.8%) achieved downstaging (ypT0-2N0) of a rectal tumor and 11 (13.8%) had a pathologically complete response (ypCR). Downstaging rates were 45% for T classification and 65% for N classification. Sphincter saving was achieved in 73 (91.3%) of the 80 patients. Of the 80 patients, 3 (3.8%) experienced grade 3 hematologic toxicity, and 2 (2.5%) had grade 3 postoperative complications such as ileus and wound dehiscence. There was no grade 4 toxicity.

Conclusion

A two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer patients showed low toxicity profiles and promising results in terms of tumor response.     

Preoperative Intensity-modulated Chemoradiotherapy with Simultaneous Integrated Boost in Rectal Cancer: Five-year Follow-up Results of a Phase II Study

BackgroundWe conducted a phase II study to investigate the feasibility and safety of preoperative radiochemo-therapy experimental fractionation, using intensity-modulated radiation therapy with simultaneous integrated boost (IMRT SIB) to shorten the overall treatment time without dose escalation in intermediate/locally advanced rectal cancer with the aim to improving treatment outcome.Patients and methodsA total of 51 patients with operable stage II–III rectal carcinoma were included between January 2014 and January 2015. Fifty patients completed preoperative IMRT treatment with an elective dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/T3 and 48.4 Gy to T4 tumour in 22 fractions, with concomitant capecitabine (825 mg/m2/12 h, including at weekends). Median follow-up was 70 months (range 11–80 m).ResultsForty-seven patients completed treatment per protocol. Acute toxicity occurred in 2 (4%) patients. R0 resection was achieved in all but 1 and pathologic complete response (pCR) in 12 (25.5%) patients who had 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) of 91.7%, 100% and 100%, respectively. The intention-to-treat analysis showed that the type of surgery significantly moderated OS and DFS, while total downstaging and pN were predictive for DFS only. For treatment per protocol 5-year OS, DFS and LC were 80.9% (95% confidence interval [CI] 69.7–92.1), 77.1% (95% CI 65.1–89.1) and 95.2% (95% CI 88.7–100), respectively. The proportion of patients with severe late (CTCAE G ≥ 3) gastrointestinal, urinary and sexual toxicity was 15%, 2% and 8% respectively, with one reported secondary carcinoma.ConclusionsPreoperative IMRT-SIB without dose escalation was well tolerated, with a low acute toxicity profile, we achieved a high rate of pCR and showed encouraging 5-year OS, DFS and LC.Key words: rectal cancer, IMRT, simultaneous integrated boost, preoperative radiochemotherapy, acute toxicity, pathologic complete response, overall survival, disease-free survival, local control, late toxicity, quality of life     

Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer

BackgroundTo evaluate capecitabine–docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC).Patients and methodsPatients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m² twice daily, days 1–14, plus docetaxel 36 mg/m², days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The primary end point was pathologic complete response (pCR) rate, evaluated separately in HER2-negative and HER2-positive cohorts. Secondary end points included clinical response rates and tolerability.ResultsThe pCR rate was 15% [95% confidence interval (CI) 7–28] in 53 patients receiving XT and 40% (95% CI 26–55) in 50 patients receiving HXT. After neoadjuvant therapy, 50 patients receiving XT and 45 receiving HXT underwent surgery. No unexpected toxicity was observed: the most common grade ≥3 adverse events were diarrhea/mucositis (30% and 20%, respectively) and grade 3 hand–foot syndrome (11% and 6%, respectively). Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort.ConclusionNeoadjuvant XT (HXT in HER2-positive disease) is highly effective in inoperable LABC, demonstrating pCR rates of 15% and 40%, respectively. This non-anthracycline-containing regimen offers obvious benefits in early disease, where avoidance of long-term cardiotoxicity is particularly important.     

Short-course Versus Long-course Neoadjuvant Therapy for Non-metastatic Rectal Cancer: Patterns of Care and Outcomes From the National Cancer Database

Introduction

The purpose of this study was to compare the utilization, pathologic response, and overall survival (OS) between long-course neoadjuvant chemoradiation (LC-CRT) and short-course neoadjuvant radiation (SC-RT) in the treatment of non-metastatic rectal cancer.