Multicenter Phase II Trial of Chemoradiation With Oxaliplatin for Rectal Cancer

2007 ◽  
Vol 26 (1) ◽  
pp. 110-117 ◽  
Author(s):  
Claus Rödel ◽  
Torsten Liersch ◽  
Robert Michael Hermann ◽  
Dirk Arnold ◽  
Thomas Reese ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Pathologic Complete Response ◽  
Sensory Neuropathy ◽  
Multimodality Treatment ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Multicenter Phase ◽  
Grade 3

PurposeTo evaluate the activity and safety of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of adjuvant XELOX in patients with rectal cancer.Patients and MethodsOne hundred ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11 investigator sites and received preoperative RT (50.4 Gy in 28 fractions). Capecitabine was administered concurrently at 1,650 mg/m2on days 1 to 14 and 22 to 35, and oxaliplatin was administered at 50 mg/m2on days 1, 8, 22, and 29. Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT. Four cycles of adjuvant XELOX (capecitabine 1,000 mg/m2bid on days 1 to 14; oxaliplatin 130 mg/m2on day 1) were administered. The main end points were activity as assessed by the pathologic complete response (pCR) rate and the feasibility of postoperative XELOX chemotherapy.ResultsAfter XELOX-RT, 103 of 104 eligible patients underwent surgery; pCR was achieved in 17 patients (16%), one patient had ypT0N1 disease, and 53 patients showed tumor regression of more than 50% of the tumor mass. R0 resections were achieved in 95% of patients, and sphincter preservation was accomplished in 77%. Full-dose preoperative XELOX-RT was administered in 96%. Grade 3 or 4 diarrhea occurred in 12% of patients. Postoperative complication occurred in 43% of patients. Sixty percent of patients received all four cycles of adjuvant XELOX, with sensory neuropathy (18%) and diarrhea (12%) being the main grade 3 or 4 toxicities.ConclusionPreoperative XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based treatment with XELOX- based multimodality treatment.

Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Claus Rödel ◽  
Gerhard. G. Grabenbauer ◽  
Thomas Papadopoulos ◽  
Werner Hohenberger ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Grade 3

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery. Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

High complete response (CR) rate in patients (pts) with esophageal carcinoma (EC) undergoing neoadjuvant combination of docetaxel and cisplatin (DC) ± cetuximab(DCE) chemoradiation therapy—a retrospective analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15093-15093
Author(s):  
T. J. Fillos ◽  
P. Hentschel ◽  
K. Watkins ◽  
M. S. Karpeh ◽  
A. Meek ◽  
...  
Keyword(s):  
Objective Response ◽  
Pathologic Complete Response ◽  
Stage Iv ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
High Rate ◽  
Phase Iii ◽  
Weekly Docetaxel ◽  
Stage Iv Disease ◽  
Grade 3

15093 Background: EC is a highly lethal disease with 5 year survival less than 15%. Surgery offers a chance for cure in early disease. Still, fewer than 20% of pts treated with surgery alone are alive at 5 years. Neoadjuvant chemoradiation offers the theoretical advantage of increasing R0 resections and reducing early local and distal metastases which may translate into improved survival. Several clinical trials have resulted in pathologic complete response (pCR) rates of 20–30%. Methods: Newly diagnosed pts with EC Stage 2A (T3) to 4 received weekly Docetaxel (D)25–30mg/m2 and Cisplatin (C)25–30mg/m2.for 6–8 weeks concurrently with radiation, 5040 cGy in 28 fractions. Cetuximab (E) 200mg/m2 was added after it became accepted treatment in head and neck cancers. Pts were scheduled 4 - 6 weeks later for surgery followed by the same chemotherapy for total of 16 weeks of treatment. Pts were assessed for time to progression, overall survival and toxicities. Results: Fifteen pts treated in 2005–6 underwent IRB approved evaluation; 11 male and 4 female, median age of 62(range 44–78) . Four had squamous cell (SCC) and 11 adenocarcinomas. Nine pts had Stage II, 4 pts stage III and 2 pts stage IV disease. Seven pts underwent surgery, all R0 resections. Four of them had pCR, one pPR (downstaged from T3 to T1) and two pts had stable disease. An additional 3 pts had radiological and endoscopic proven CR (medically not surgical candidates) for an objective response (CR+PR) in 8 out of 15 pts (3 SCC and 5 adenoca). Five out of 9 receiving DC had an objective response while 3 of 6 receiving DCE responded. Five pts progressed prior to surgery. Grade 3/4 neutropenia occurred in 2, nausea in 3, and 1 pt experienced Grade 3 dehydration. Four patients required dose reductions by 20%. Six patients had one cycle and 2 had 3 cycles delayed by one week each. Conclusions: Neoadjuvant chemoradiation treatment with weekly Docetaxel and Cisplatin ± Cetuximab is tolerable with high rate of CRs. There was no observed difference in response with the addition of cetuximab. A Phase III study is suggested. No significant financial relationships to disclose.

Residual rectal cancer after preoperative radiochemotherapy (ypT1-2): An indication for local excision instead of radical surgery?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 546-546
Author(s):  
Thilo Sprenger ◽  
Hilka Rothe ◽  
Lena-Christin Conradi ◽  
Kia Homayounfar ◽  
Tim Beissbarth ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Excision ◽  
Bowel Wall ◽  
Radical Surgery ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Phase Iii ◽  
Preoperative Radiochemotherapy ◽  
Cancer Trial

546 Background: Preoperative radiochemotherapy (RCT) followed by total mesorectal excision (TME) has improved local tumor control and led to a significant tumor downstaging. For patients with pathologic complete response (ypT0) as well as residual tumor restricted only to the bowel wall (ypT1-2) local excision has increasingly been discussed to avoid significant morbidity and functional deficits associated with TME. Therefore we investigated the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with ypT0, ypT1-2 and ypT3-4 rectal cancers, respectively. Methods: TME specimens from 81 patients with locally advanced rectal cancer treated with neoadjuvant RCT within the phase III German Rectal Cancer Trial CAO/ARO/AIO-04 were evaluated. The entire mesorectal compartment was screened microscopically after complete paraffin embedding. The number and localization of all detectable LN metastases was specified in relation to the primary tumor. Results: Whereas 50 patients (62%) had ypT3-4 carcinomas after neoadjuvant RCT 20 patients (25%) presented with residual tumor within the bowel wall (ypT1-2). 11 patients (14%) had pathologic complete response (ypT0). 28 ± 13.7 LN were detected per specimen. 25 patients (31%) had residual LN metastases after RCT. Although the incidence was higher in the ypT3-4 group (40% ypN+) still 25% of patients in the ypT1-2 group had a mean number of 2.2 residual LN metastases. 55% of these metastases were located afar from the primary lesion in the proximal mesorectum. No patient with ypT0 status had residual LN metastases. Conclusions: Even in patients with good response and tumors restricted only to the bowel wall (ypT1-2) after RCT there is a considerable risk for residual LN metastases. The majority of metastases were located clearly outside the tumor region. Local excision of residual rectal cancer would be accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in those patients.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the phase III KRISTINE study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Miguel Martin ◽  
Kyung Hae Jung ◽  
Chiun-Sheng Huang ◽  
Nadia Harbeck ◽  
...  
Keyword(s):  
Randomized Study ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Her2 Positive ◽  
Free Survival ◽  
Post Surgery ◽  
Grade 3

500 Background: KRISTINE compared neoadjuvant chemotherapy plus dual HER2- blockade (HP) with T-DM1 plus P (T-DM1+P), a targeted regimen that omits standard chemotherapy. T-DM1+P resulted in a lower pathologic complete response (pCR) rate, but a more favorable safety profile. Here we present the final outcomes from KRISTINE. Methods: KRISTINE (NCT02131064) was a randomized study of T-DM1+P versus docetaxel, carboplatin, and H plus P (TCHP). Patients with HER2-positive stage II–III BC received 6 cycles of neoadjuvant T-DM1+P or TCHP q3w. Patients receiving T-DM1+P continued adjuvant T-DM1+P; patients receiving TCHP received adjuvant HP, for 12 cycles in each arm. Patients in the T-DM1+P arm without pCR were encouraged to receive standard adjuvant chemotherapy before adjuvant T-DM1+P. Secondary endpoints, analyzed with descriptive statistics, included event-free survival (EFS; all events pre- and post-surgery), invasive disease-free survival (IDFS; invasive events post-surgery), overall survival and safety. Results: At median follow-up of 37 months, EFS favored TCHP (HR = 2.61 [95% CI: 1.36–4.98]), due to more locoregional progression events in the T-DM1+P arm before surgery (6.7% vs 0; Table). pCR was associated with reduced risk of an IDFS event (HR = 0.24 [95% CI: 0.09– 0.60]) regardless of treatment arm. There were 5 deaths (2.3%) in the TCHP arm and 6 (2.7%) in the T-DM1+P arm. There were more grade ≥3 AEs with TCHP but a higher rate of AEs leading to treatment discontinuation with T-DM1+P. Conclusions: EFS numerically favors TCHP due to locoregional progression events with T-DM1+P prior to surgery. T-DM1+P was associated with fewer grade ≥3 AEs but increased treatment discontinuation. Clinical trial information: NCT02131064. [Table: see text]

scholarly journals Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan

2021 ◽  
pp. 790-796
Author(s):  
Muhammad Atif Mansha ◽  
Asmara Waheed ◽  
Tabinda Sadaf ◽  
Asma Rashid ◽  
Nabia Irfan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Circumferential Resection Margin ◽  
Randomized Clinical Trials ◽  
Resection Margin ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Response Rates ◽  
Complete Response ◽  
Grade 3

PURPOSE To report the toxicity and pathologic response rates after adding neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by concurrent radiation and capecitabine (CAPRT) and surgery in patients with locally advanced rectal cancer. MATERIALS AND METHODS We retrospectively analyzed medical records of 301 patients between January 2007 and December 2014. Patients were treated with four cycles of neoadjuvant chemotherapy comprising CAPOX, followed by radiotherapy at doses of 45-54 Gy in 25-30 fractions with concurrent capecitabine. A response assessment scan was performed at 4-6 weeks postradiation followed by surgical evaluation at 6-8 weeks. Pathologic tumor and nodal response rates as well as circumferential resection margin were assessed on surgical specimens. RESULTS The median age of the patients was 43 years (range, 16-78). Overall, 227 (75.4%) patients were able to complete four cycles of CAPOX. Neoadjuvant chemotherapy was well-tolerated with no serious adverse effects. The most common toxicity was diarrhea (grade 2, n = 108; 35.8%; grade 3, n = 57; 18.9%; grade 4, n = 25; 8.3%) followed by neuropathy (grade 2, n = 132; 43.8%; grade 3, n = 54; 17.9%) and oral mucositis (grade 2, n = 108; 35.8%; grade 3, n = 47; 15.6%; grade 4, n = 9; 2.99%). A total of 229 (76.1%) patients underwent surgery. Pathologic complete response was seen in 52 (22.7%; 95% CI, 13 to 28), whereas 200 (87.3%; 95% CI, 82 to 99) patients had a negative circumferential resection margin on pathology. CONCLUSION Neoadjuvant chemotherapy with CAPOX before CAPRT and planned total mesorectal excision surgery result in good tumor regression and substantial pathologic complete response rates with acceptable toxicity. With growing interest in organ preservation in rectal cancer, the strategy of completing all chemotherapy and chemoradiotherapy before planned surgery offers a favorable paradigm. However, further randomized clinical trials are needed to support this evidence.

Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 604-604
Author(s):  
J. A. Gutierrez ◽  
G. Martinez-Martinez ◽  
A. J. Silva ◽  
J. Gomez Rangel ◽  
M. Palmerin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
Dermatologic Toxicity ◽  
Grade 3 ◽  
Experienced Grade

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.

The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 579-579 ◽  
Author(s):  
Brian G. Czito ◽  
Mary Frances Mulcahy ◽  
Dustin A. Deming ◽  
Houman Vaghefi ◽  
Gayle S. Jameson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Parp Inhibitor ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Post Surgery ◽  
Tumor Downstaging ◽  
Grade 3 ◽  
Dose Proportional

579 Background: Patients (pts) with LARC treated with neoadjuvant C/RT and then surgery have low rates of pathologic complete response (ypCR) and significant relapse rates. V is a potent, orally bioavailable PARP inhibitor that has been shown to enhance the efficacy of chemotherapy and RT in preclinical models. This study sought to establish the recommended phase 2 dose (RPTD), as well as to assess safety, pharmacokinetics (PK), and preliminary activity of V + RT/C in pts with LARC. Methods: Pts with stage II-III rectal cancer received RT (50.4Gy/1.8Gy/fraction) with C (825 mg/m2 BID) five days per week (W) for 5.5W. Dosing of V (BID, 20mg-400mg) continued from W1D2 to 2 days past RT. Pts underwent surgery 5-10W following RT. Assessments included identification of RPTD with the Exposure Adjusted Continual Reassessment Method, adverse events (AEs), PK, and pathological response (ypCR and tumor downstaging rates). Results: As of August 5, 2014, 30 pts have been enrolled, 24/6 male/female, median age 58 yrs; 1 pt discontinued due to an AE. The most common treatment-emergent AEs possibly or probably related to V (>15% pts, n >4) were nausea (40%), fatigue (37%), diarrhea (30%), vomiting (20%), and dysgeusia (17%). One grade 3/4 event each of anemia and lymphopenia and 2 grade 3/4 events of diarrhea were deemed at least possibly related to V. Two dose limiting toxicities (DLTs) occurred: 1 at 70 mg BID V (radiation skin injury requiring dose interruption); 1 at 400 mg BID (nausea and vomiting requiring discontinuation). The RPTD is 400 mg BID of V in combination with RT/C. PK results from 16 pts suggest that V PK was approximately dose proportional when administered with RT/C and that V had no effect on the PK of C. To date, 18/25 (72%) pts have been downstaged post-surgery; with 7/25 (28%) achieving ypCR. Conclusions: V at 400 mg in combination with RT/C has an acceptable safety profile. 72% of 25 evaluable patients had tumor downstaging post-surgery, including 28% with ypCR. Dose escalation of V resulted in approximately dose-proportional increases in the V PK with no clear effect on C PK. Clinical trial information: NCT01589419.

scholarly journals Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia-yi Li ◽  
Xuan-zhang Huang ◽  
Peng Gao ◽  
Yong-xi Song ◽  
Xiao-wan Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Individual Patient Data ◽  
Tumor Regression ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Direct Calculation ◽  
Complete Response ◽  
Patient Data ◽  
Term Survival

Abstract Background Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). Methods The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan–Meier curves. Results The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177–0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205–0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. Conclusions Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

scholarly journals Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia

2019 ◽  
Vol 53 (4) ◽  
pp. 465-472
Author(s):  
Mojca Tuta ◽  
Nina Boc ◽  
Erik Brecelj ◽  
Mirko Omejc ◽  
Franc Anderluh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Distant Recurrence ◽  
High Risk Factors ◽  
Grade 3

Abstract Background In the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence. Patients and methods Patients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8–10 weeks after completition of CRT. Results From November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p < 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR. ConclusionsTotal neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.

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