scholarly journals Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rongzhen Li ◽  
Qiaoxuan Wang ◽  
Bin Zhang ◽  
Yan Yuan ◽  
Weihao Xie ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Local Treatment ◽  
Rectal Adenocarcinoma ◽  
Stage Iv ◽  
Treatment Schedule ◽  
Term Survival

Abstract Background The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. Methods Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. Results A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3–4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. Conclusions Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Effect of adjuvant chemotherapy following pathologic complete response on long-term survival in rectal cancer: A propensity score matched analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 717-717 ◽  
Author(s):  
Ali Mokdad ◽  
Sergio Huerta ◽  
Rebecca M Minter ◽  
John C. Mansour ◽  
Michael A. Choti ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Term Survival

717 Background: The role of adjuvant chemotherapy following resection in patients with rectal cancer that achieve pathologic complete response (pCR) after neoadjuvant therapy is unclear. Current data have been limited by small sample size series. This study examined the impact of adjuvant chemotherapy following pCR on overall survival in a national cohort of patients. Methods: Patients with rectal adenocarcinoma were identified in the National Cancer Data Base between 2006 and 2012. Those with locally advanced tumor (clinical stage II or III) that achieved pCR (defined as ypT0N0 in surgical specimens) after neoadjuvant chemoradiotherapy (nCRT) were included in the study. We matched by propensity score patients that received adjuvant chemotherapy (ACT) and patients that did not receive postoperative treatment (no-ACT) controlling for demographic as well as perioperative patient and tumor characteristics. Overall survival was compared using a Cox proportional hazards model. Results: We identified 2,543 patients (ACT: 732, no-ACT: 1,811 patients) with resected locally advanced rectal adenocarcinoma that achieved pCR after nCRT. Among patients that received ACT, 711 were matched with 711 patients in the no-ACT group. Adjuvant chemotherapy was associated with improved overall survival compared to no-ACT (hazard ratio[HR] = 0.46, 95% confidence interval [CI] = 0.29 – 0.75). Overall survivals at 1, 3, and 5 years in the ACT and no-ACT groups were 100% vs 98% (P=0.1), 98% vs 94% (P<0.01), and 94% vs 89% (P<0.01), respectively. In subgroup analyses, adjuvant chemotherapy improved overall survival in patients with clinical stage II (HR = 0.43, 95% CI = 0.22 – 0.85) as well as stage III tumor (OR = 0.50, 95% CI = 0.26 – 0.98). Among patients that received adjuvant chemotherapy, there was no difference in overall survival between single agent and multiagent regimens (HR = 1.37, 95% CI = 0.57 – 3.29). Conclusions: Adjuvant chemotherapy may providea small long-term survival benefit in patients with resected locally advanced rectal cancer and pCR after nCRT.

Delays in adjuvant chemotherapy following AP resection for low rectal cancer: Audit results and implications for clinical practice.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 562-562
Author(s):  
S. S. Nimalasena ◽  
A. M. Gaya
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Neoadjuvant Chemoradiotherapy ◽  
Wound Dehiscence ◽  
Low Rectal Cancer ◽  
Wound Complications ◽  
Phase Ii Studies

562 Background: Abdominoperineal resection (APR) remains the surgical procedure of choice for low rectal cancer. Historically, it has been associated with high rates of postoperative haemorrhage, infection, and wound dehiscence. The perineal wound is particularly at risk, with rates of 16-41% reported. This may delay adjuvant chemotherapy and adversely affect survival. Methods: Patients who underwent APR in our cancer network between March 2009 and June 2010 were identified. Records were reviewed with respect to complications and any impact on adjuvant chemotherapy. Results: 28 patients underwent APR. The majority had Duke's C (68%) and Duke's B (14%) tumors. All received neoadjuvant chemoradiotherapy (CRT) to 45-54Gy with capecitabine 825 mg/m2 BD. Adjuvant chemotherapy (CAPOX, FOLFOX or capecitabine) was planned in 25/28 (89%) patients. 2 declined, and of the remaining 23, 12 patients (52%) could not receive chemotherapy (Table). Of patients who received adjuvant chemotherapy, the average delay in starting was 2 weeks. At the time of reporting, 25/28 (86%) patients are alive without disease recurrence. One patient who did not receive adjuvant chemotherapy due to wound dehiscence, has recurrent pelvic disease, and is receiving best supportive care. Two patients died of metastatic disease; one could not receive adjuvant chemotherapy due to wound infection. Conclusions: Our audit has highlighted that a significant proportion of patients undergoing APR do not receive adjuvant chemotherapy on time due to wound complications. Often the time taken for wound healing exceeds 3 months, by which time the benefit of chemotherapy is negligible. Phase II studies of neoadjuvant chemotherapy prior to CRT for locally advanced rectal cancer have shown impressive progression-free and overall survival rates, with good compliance rates and favorable toxicity profiles. Further studies are needed. Patients with low rectal tumours who require APR, should be considered for a neoadjuvant chemotherapy approach. [Table: see text] No significant financial relationships to disclose.

Perioperative chemotherapy using FOLFOX with panitumumab for locally advanced rectal cancer: Phase II trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 502-502
Author(s):  
Mitsuyoshi Ota ◽  
Jun Watanabe ◽  
Atsushi Ishibe ◽  
Hirokazu Suwa ◽  
Masashi Momiyama ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Reduction Rate ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Reduction

502 Background: Neoadjuvant chemotherapy for locally advanced rectal cancer is required to achieve tumor reduction when skipping routine use of preoperative radiation therapy. It is known that EGFR inhibitor has impact on early tumor shrinkage in metastatic colorectal cancer. We evaluated the effect of preoperative infusional fluorouracil, leucovolin, and oxaliplatin (FOLFOX) with panitumumab. Methods: Forty-three patients with clinical stage III rectal cancer without invasion to other organs were enrolled in this multicenter phase II trial. All patients had KRAS wild tumors confirmed by biopsy. Patients received six cycles of FOLFOX with panitumumab. Reduction rate of primary tumor was measured by T2 weighted sagittal image of magnetic resonance imaging. Excluding patients whose disease progressed after the six cycles, total mesorectal excision was performed two weeks after neoadjuvant chemotherapy. After surgery, adjuvant chemotherapy with six cycles of FOLFOX without panitumumab was planned before diverting stoma closure. The primary outcome was the response rate of the primary lesion. Results: Between January 2012 and December 2014, 42 out of 43 patients completed preoperative chemotherapy; one patient did not complete the regimen due to grade III neutropenia. There was no progressive disease in the 42 patients and response rate was 69.8% in this series. Average reduction rate of the primary lesion was 47.6%. All of the 43 participants had R0 resections without mortality or severe complications. Pathological complete response rate to chemotherapy was 7.0% (3 of 43). Thirty-eight out of 43 patients started adjuvant chemotherapy and 32 patients completed the regimen. Grade 3 or worse peripheral neuropathy was not seen during neoadjuvant chemotherapy and seen in 2.6% (1 of 38) during adjuvant chemotherapy. Conclusions: Periopative chemotherapy using FOLFOX with panitumumab seemed to have two advantages; one is tumor reduction which enables skipping neoadjuvant radiation therapy, the other is safely administering a larger dose of chemotherapy than adjuvant only in locally advanced rectal cancer. Additional impact of EGFR inhibitor should be followed in long term results. Clinical trial information: UMIN000006039.

INNOVA: A phase II randomized study comparing INterval versus NeOadjuVAnt chemotherapy in magnetic resonance imaging-defined high risk rectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS879-TPS879
Author(s):  
Ramakrishnan Ayloor Seshadri ◽  
Trivadi S. Ganesan ◽  
Arunkumar M N ◽  
Shirley Sundersingh
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Rectal Cancers

TPS879 Background: Patients with rectal cancers treated with neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy are not exposed to systemic doses of chemotherapy until very late in the treatment schedule. Preoperative chemotherapy, either in the neoadjuvant or interval setting can lead to early treatment of micrometastasis, improve the tumor response and possibly the overall survival. Phase II studies of neoadjuvant chemotherapy in rectal cancer have shown good response to chemotherapy with no tumor progression and good compliance. A phase II study evaluating the effect of giving chemotherapy in the interval waiting period between chemoradiation and surgery has shown acceptable toxicity and high pathological complete response rates. Methods: This single centre, randomized, open label, phase II trial compares the safety and efficacy of two pre-operative regimens in locally advanced MRI defined high-risk rectal cancers. Based on the Simon optimal two-stage design, 94 patients will be randomised to either Arm A [3 cycles of neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by chemoradiation (50.4 Gy with capecitabine) and then surgery] or Arm B [neoadjuvant chemoradiation followed by 3 cycles of interval chemotherapy and then surgery]. Patients in both arms receive 3 cycles of adjuvant chemotherapy. The primary end-point is the pathological complete response rate. Secondary end-points include frequency and severity of adverse events, RO resection rates, tumor regression grading and compliance to treatment. The inclusion criteria: age 18 to 70 years; ECOG performance status 0-2; non-metastatic, locally advanced rectal cancer with any one of the following features on high-resolution thin slice MRI: any T3/T4 tumor in the lower rectum, T3c/T3d/T4 tumor in the mid rectum, N2 disease, threatened mesorectal fascia, or extramural vascular invasion. Patients are randomly assigned to one of the two intervention arms in a 1:1 ratio. Prespecified activity goal for the first stage of accrual was met; second stage accrual began in July 2017. Clinical trial information: CTRI/2015/01/005385.

Neoadjuvant and adjuvant methotrexate, cisplatin, and fluorouracil in multimodal therapy of head and neck cancer.

1989 ◽  
Vol 7 (7) ◽  
pp. 838-845 ◽  
Author(s):  
E E Vokes ◽  
W J Moran ◽  
R Mick ◽  
R R Weichselbaum ◽  
W R Panje
Keyword(s):  
Head And Neck Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Head And Neck ◽  
Continuous Infusion ◽  
Neck Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Local Therapy ◽  
Stage Iv

To increase the complete response (CR) rate of patients with locally advanced head and neck cancer after three cycles of neoadjuvant chemotherapy, we added sequential methotrexate to the combination of cisplatin and continuous infusion fluorouracil (5-FU). We also evaluated the feasibility of administering three additional cycles of the same regimen as adjuvant chemotherapy. Thirty-eight patients were treated; the median age was 53 years and 36 patients had stage IV disease. Chemotherapy consisted of methotrexate 120 mg/m2 followed 24 hours later by cisplatin 100 mg/m2 and a five-day continuous infusion of 5-FU at 1,000 mg/m2/d. Of 34 patients evaluable for response to neoadjuvant chemotherapy, nine had a CR, 21 a partial response (PR), two a minimal response (MR), and one patient each stable disease (SD) and no response (NR). Of 31 patients who received local therapy, 15 were treated with surgery and radiotherapy and 16 with radiotherapy alone. Of 25 patients eligible to receive adjuvant chemotherapy only ten received all three intended cycles, while 15 received less or no adjuvant chemotherapy because of patient refusal, cumulative toxicity, or early disease progression. With a median follow-up time of 39 months, the median survival is estimated to be 20 months. Of eight patients with nasopharyngeal or paranasal sinus cancer, none has had disease recurrence. Patients with good initial performance status and low N-stage also had a significant survival advantage. Chemotherapy-related toxicities consisted mainly of mucositis, requiring 5-FU dose reduction in the majority of patients; similar toxicities were exacerbated in the adjuvant setting. The addition of methotrexate did not increase the CR rate over what has been reported for the combination of cisplatin and 5-FU alone. Certain subsets of patients appear to have a good prognosis when treated in this fashion. The administration of adequate adjuvant chemotherapy in patients with head and neck cancer remains difficult due to toxicity and poor patient compliance.

HER2 status in locally advanced rectal cancer and metachronous metastases: Opportunity for a new therapeutic approach?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3600-3600
Author(s):  
Lena-Christin Conradi ◽  
Hanna Styczen ◽  
Thilo Sprenger ◽  
Kia Homayounfar ◽  
Hendrik A. Wolff ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Clinicopathological Parameters ◽  
Term Survival ◽  
Primary Tumors ◽  
Her 2 ◽  
Metachronous Metastases

3600 Background: Even though the implementation of multimodal treatment strategies including neoadjuvant radiochemotherapy (RCT) has led to improved survival distant metastases are still limiting the prognosis of rectal cancer patients. In this context, we investigated the HER-2 status in rectal cancer patients, UICC stages II and III. Our aim was to assess the HER-2 positivity rate in primary tumors and metachronous metastases. Methods: In this study 264 rectal cancer patients (192 male, 72 female; median age 64 years) from phase-II/-III-trials of the German Rectal Cancer Study Group (CAO/ARO/AIO-94 and 04) were included. HER-2 status was determined pretherapeutically in tumor biopsies as well as resection specimens and metachronous metastases (n=27) using immunohistochemistry (IHC0 to IHC3+) scoring and S-ISH-amplification detection. Tumors with IHC3+ or S-ISH ratio ?2.0 were classified as HER-2 positive; results were correlated with clinicopathological parameters and long-term survival. Results: A positive HER-2 status was found in 12.4% of pre-treatment biopsies, in 29.3% of the resection specimens and 22.2% (n=6) of metastases. With a median follow-up of 46.5 months patients with HER-2-positivity showed better disease free survival (p=0.06) and cancer-specific survival (CSS, p=0.05). The 5-years survival rate was 96.4% (HER-2-positive) versus 79.5% (HER-2-negative). In multivariate analyses HER-2 status was as an independent (p=0.0053) predictor for CSS along with (y)pN-status (p<0.0001) and R-status (p=0.023). Conclusions: HER-2 amplification is detectable in a significant proportion (about 30%) of primary tumors of patients with advanced rectal cancer. Furthermore HER-2 amplification was detectable in 22% of resected metachronous metastases during follow-up. Therefore HER-2 represents a promising target and should be further assessed within prospective clinical trials.

Comparison of magnetic resonance imaging and histopathological response to neoadjuvant chemotherapy in locally advanced rectal cancer: The GEMCAD 0801 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14097-e14097
Author(s):  
Gina Brown ◽  
Uday Bharat Patel ◽  
Jesus Santos Cores ◽  
Maria Isabel Gil Garcia ◽  
Juan Ramón Ayuso ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Length Change ◽  
Post Treatment ◽  
Moderate Level ◽  
Level Of Agreement ◽  
Response To Neoadjuvant Chemotherapy

e14097 Background: MRI methods for rectal cancer response assessment post chemoradiotherapy include post treatment T staging(ymrT), tumor regression grading(mrTRG) and length change/modified RECIST measurement. The usefulness of MRI in evaluating response to neoadjuvant chemotherapy has not been investigated. We assessed the reproducibility and agreement of these three parameters with histopathological T and TRG stage(ypT, pTRG). Methods: 28 eligible patients were enrolled in a prospective phase II trial to evaluate safety and efficacy of neoadjuvant CAPOX-B in patients with MRI defined T3 rectal adenocarcinoma. Patients received 4 cycles of Cap 2000 mg/m2(d1-14),Ox 130 mg/m2(d1) and B 7.5 mg/kg(d1) every 3 weeks(last cycle without B). Seven radiologists assessed MRIs using the following categories: ymrT (T0-T4 using T3 substaging), mrTRG (1-5), and length change(Stable disease, Complete response,Partial response). Agreement was assessed by kappa (central reviewer data verses each local centre reviewer).Agreement between central reviewer MRI results and both pathology endpoints was also assessed. Results: 24 patients had evaluable pre and post chemotherapy imaging and pathology (4 did not have post treatment MRI). Thirteen patients had good response (ypT0-3a) and 11 had poor response (>ypT3a). Sixteen patients had good pTRG(2-4) and 8 had poor pTRG(0&1). ymrTRG showed a moderate level of reproducibility;K=0.45-0.58. ymrT showed a fair to moderate level of agreement;K=0.2-0.53. Length assessment also showed a fair level of agreement; K=0.21-0.38. ymrTRG showed 75% agreement with ypT(16/22); K=0.49(0.13-0.84) and 79% agreement with pTRG(19/24); K=0.55(0.22-0.88). ymrT showed a fair level of agreement with ypT;K=0.21, pTRG;K=0.2, length assessment showed slight agreement with ypT;K=0.1, pTRG;K=0.1. Conclusions: This is the first study to show MRI can evaluate response of rectal cancer following neoadjuvant chemotherapy. As mrTRG showed best agreement with pathology, we recommend mrTRG as the preferred method of post treatment assessment in this setting.

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