Neoadjuvant Chemotherapy For Rectal Cancer Research Articles

Assessment of the effectiveness of neoadjuvant chemotherapy for rectal cancer by MRI and PETCT: a meta-analysis

Assessment of the effectiveness of neoadjuvant chemotherapy for rectal cancer by MRI and PETCT: a meta-analysis

Predictive Value of Inflammatory Indicators on the Efficacy of Preoperative Neoadjuvant Chemotherapy in Patients With Locally Advanced Rectal Cancer

Objective: To investigate the relationship between peripheral blood neutrophil‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), platelet‐to‐lymphocyte ratio (PLR), lymphocyte‐to‐C‐reactive‐protein ratio (LCR), and monocyte‐to‐leukocyte ratio (MWR) and the efficacy of neoadjuvant chemotherapy (NAC) for patients with locally advanced rectal cancer before and after chemotherapy.Methods: Seventeen rectal cancer patients who underwent NAC at West China Hospital of Sichuan University from March 31, 2022, to April 30, 2024, were selected as the study subjects, and the predictive value of peripheral blood NLR, LMR, PLR, LCR, and MWR were included in the least absolute shrinkage and selection operator (LASSO) regression analysis for the pathological efficacy, and the significant variables were screened out and the nomogram was constructed from them. Decision curve analysis (DCA) was applied to evaluate the predictive performance of the model.Results: LASSO regression screened three predictive variables of NLR, LMR and LCR before neoadjuvant therapy that could predict pathological complete remission (pCR), as well as changes in PLR, LCR, and MWR after neoadjuvant therapy that could predict chemotherapy inefficacy. Nomograms and DCA curves were drawn based on the variables, and internal validation showed that the model had good predictive ability.Conclusion: The comprehensive hematological prediction model for effective NAC in rectal cancer has a good predictive ability for NAC efficacy, which can provide guidance for individualized patient treatment.

Do treated rectal tumors appear differently on MRI after chemotherapy versus chemoradiotherapy?

Increasing studies have focused on neoadjuvant chemotherapy (NCT) in rectal cancer. However, few studies explored the differences in radiographic variation between patients treated with NCT and neoadjuvant chemoradiotherapy (NCRT). Stage II/III rectal cancer patients from March 2016 to December 2019 meeting the criteria treated with NCRT or NCT were included. MRI features, including tumor location, longitudinal length, DWI signal, MRI tumor regression grade (mrTRG), and radiomic texture features, before and after neoadjuvant treatments were reviewed. 116 patients with NCRT and 61 with NCT were analyzed. Among these patients, 46 patients in the NCRT group and 18 in the NCT group were responders with pathological TRG0-1. Within these responders, the mean tumor longitudinal length regression rate (TLRR) of the NCT group was 60.08 ± 11.17%, which was significantly higher than the 50.73 ± 15.28% of the NCRT group (p = 0.010). The proportion of high signal in the DWI image after NCT was higher than that of the NCRT group (88.89% vs 50.00%, p = 0.004). NCT responders had significantly higher median change rates than those of NCRT responders in 11 radiomic features, especially those shape features. MRI images change differently between responders treated with NCRT and those with NCT in rectal cancer. The tumor volumetry and some radiomic features change more obviously in NCT responders, and the tumor signal changes more obviously in NCRT responders. During the evaluation of the response of the tumor to the neoadjuvant treatments, images of patients should be treated differently.

Resolving the tissue response to neoadjuvant chemotherapy in rectal cancer

In this issue of Cell Reports Medicine, Qin etal.1 present a comprehensive single-cell transcriptomics analysis of the tumor microenvironment of rectal cancer tumors before and after neoadjuvant chemotherapy.

Treatment response prediction of neoadjuvant chemotherapy for rectal cancer by deep learning of colonoscopy images.

In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy.

Total Neoadjuvant Chemotherapy in Rectal Cancer: Current Facts and Future Strategies.

Despite preoperative chemoradiotherapy (CRT) and total mesorectal excision improving the local control for locally advanced rectal cancer (LARC), oncologic outcomes and survival were not significantly improved because the main prognostic factor is distant metastasis. Thus, total neoadjuvant chemotherapy (TNT) as a novel approach has been proposed to improve chemotolerance. Since the first randomized phase II trial of TNT versus standard CRT demonstrated in 2012, many prospective and retrospective studies have been published. The initial consensus from TNT studies was that pathological complete response, pathological response of the main tumor, and local control are more favorable at TNT than at CRT. Furthermore, recent studies such as the PAPIDO trial and PRODIGE 23 trial made a major breakthrough of the treatment of TNT, showing that TNT improves the disease-free survival compared to standard treatment with long-course CRT. In addition, several innovative findings of TNT were clarified by prospective phase II trial. In this review, we summarize the most recent advances in TNT based on the findings of pivotal clinical trials for patients with LARC.

INNOVA: Interval or neoadjuvant chemotherapy in rectal cancer—A phase II randomized study comparing interval versus neoadjuvant chemotherapy in magnetic resonance imaging-defined high-risk rectal cancer.

91 Background: Total neoadjuvant treatment is a promising option in rectal cancer. We aim to compare neoadjuvant versus interval chemotherapy in high risk rectal cancer to identify the optimal sequencing of treatment. Methods: Using a Simon two-stage design, newly diagnosed MRI defined high risk rectal cancer patients were randomly assigned in a 1:1 ratio to receive three 21 day cycles of chemotherapy with Capecitabine 1000 mg/m2 and Oxaliplatin 130 mg/m2 either before (Arm A-neoadjuvant) or after (Arm B-interval) chemoradiation followed by surgery. Primary end point was the pathological complete response (pCR) following surgery. A heirarchial model was used to assess the primary and secondary end points (toxicity and compliance) and compare the two regimens. (Clinical Trial Registry of India No. CTRI/2015/01/005385). Results: In this single centre study conducted between November 2015 and February 2020, 42 patients were randomised in the first stage. A pCR was seen in 4 patients in Arm A and 6 in Arm B. Hence another 52 patients were randomised in the second stage of which an additional 3 and 2 patients had a pCR leading to an overall pCR of 7 and 8 patients (15.5% vs 17% and 18.4% vs 19.5% in the intent-to-treat and per-protocol populations in Arm A and B respectively. This exceeded the minimum predetermined number of 5 pCR needed to qualify for further evaluation for each arm. Grade ≥3 toxicity was observed in 2.2% of 132 cycles and 4.6% of 129 cycles of chemotherapy delivered in 45 and 43 patients in Arm A and B respectively while 11/43 (25.5%) and 10/47 (21.2%) patients experienced grade ≥3 toxicity during chemoradiation. Treatment break of > 7 days was seen in 23.2% and 29.7% of patients in Arm A and B respectively while 93.3% in Arm A and 100% of patients in Arm B completed all 3 planned cycles of pre-operative chemotherapy. A non-significant trend towards greater pathological downstaging was seen in Arm B than in Arm A (ypT1-2 39% vs 26.3%; p = 0.1 and ypN0 68.3% vs 57.9%; p = 0.5 respectively). Conclusions: In this phase two study, both neoadjuvant and interval chemotherapy emerged eligible for further evaluation against the standard of care in a future phase III study. Although we could not pick one winner based on pCR, toxicity or compliance, the greater downstaging observed with interval chemotherapy suggests it could play a greater role in an organ preservation approach. Clinical trial information:CTRI/2015/01/005385, UTN no: U111111650578.

Review and Updates on Approaches to Neoadjuvant Chemotherapy in Rectal Cancer

The currently established standard of care treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant fluorouracil and oxaliplatin. The body of evidence that supports this treatment has grown over the last 20 years. However, recent advances and ongoing studies seek to further evaluate the role of neoadjuvant chemotherapy with and without radiation and total neoadjuvant therapy (TNT). In this article, we review the current literature as well as investigate the emerging role of TNT for patients with LARC and comment on updates utilizing combination neoadjuvant chemotherapy in early-stage rectal cancer. Evidence for the current standard of neoadjuvant CRT comes from well-established randomized phase III trials as well as emerging evidence on merits of TNT. There is a growing body of literature including retrospective analysis and ongoing clinical trials that look at upfront induction chemotherapy in addition to CRT prior to surgical resection leading to more effective delivery of systemic therapy and increases in response to treatment. Neoadjuvant combination chemotherapy is also being investigated in early-stage low rectal tumors to see if rates of local excision will increase compared to radical excision. Current evidence continues to support neoadjuvant CRT as the standard treatment for LARC. There is an increasing body of evidence to support TNT in LARC as an effective treatment strategy that better ensures delivery of systemic therapy leading to higher rates of complete response (CR) and is encouraging for the development of non-operative protocols. There is ongoing evaluation looking at the benefit of novel sensitizers added to neoadjuvant therapy and ongoing investigation into upfront combination chemotherapy with selective use of radiation in upper rectal cancers.

Complete Clinical Response after Short-course Radiation and Sequential Multi-agent Chemotherapy for Non-operative Treatment of Rectal Adenocarcinoma

Recent data show promise of short-course radiation (SCR) plus total neoadjuvant chemotherapy for rectal cancer. We evaluated the complete clinical response (cCR) rate and toxicity in patients who were treated with SCR followed by multi-agent chemotherapy (CH) and non-operative intent. From January 2018 to May 2019, 90 patients with newly diagnosed, non-metastatic rectal adenocarcinoma were treated with SCR-CH and non-operative intent at our institution. Patients received 25 Gy/5 fx to the pelvis with an optional primary boost to 30 Gy. Involved extra-mesorectal pelvic lymph nodes were boosted to 35 Gy. CH was initiated after RT. CR was assessed after CH by digital rectal examination, MRI pelvis, and endoscopy. Patients with a cCR were followed with these assessments every 3 months. Patients with a partial CR received surgery. Follow-up was calculated from CH completion. GI toxicity was graded per CTCAE v5. Of the 90 patients [median age 61 (range 25-91)], 86 (96%) had locally advanced disease (T3/4 or node positive) and median tumor size 4.6 cm (range 1.5-11 cm). The median distance from anal verge was 7 cm (range 0-13 cm). All patients completed prescribed RT. Five patients received CH ≤5 cycles due to poor tolerance. Among patients who completed CH ≥6 cycles, the initial cCR rate was 51% (43/85) overall and 49% (40/81) for patients with locally advanced disease. Median follow-up was 9.7 mos (range 0.7-21 mos) for living patients, and 44% (37/85) patients had continued cCR at last follow up. For patients with primaries ≤2 cm from anal verge, 6 (6/20, 30%) patients had an initial cCR and 5 (25%) patients had a continued cCR at last follow up. Among non-operative patients, 18 (49%) had no late GI toxicities and 0 had late G3/4 GI toxicities. In the 42 patients with a partial CR, 60% underwent low anterior resection, 29% underwent abdominoperineal resection, and 9.5% underwent transanal excision or proctectomy. Seven of 85 patients had local regrowth at a median of 8.5 mos (range 2.3-12 mos) after SCR-CH. Six cases occurred in non-operative patients requiring salvage surgery at a median of 6.0 (range 4.8-15) mos after completion of SCR-CH. Four (4/90, 4.4%) patients developed metastatic disease, all of whom had an initial partial CR and had undergone surgery. Our preliminary data show that SCR-CH can result in cCR and organ preservation in patients with locally advanced and/or low-lying rectal cancer with acceptable GI toxicity. Further follow-up is required to evaluate the durability of response and toxicity.Abstract 96; TablecT StageT212 (13%)T360 (67%)T418 (20%)cN StageN022 (24%)N127 (30%)N241 (46%)Group StageI5 (6%)II17 (19%)IIIA5 (6%)IIIB41 (45%)IIIC22 (24%)RT (Gy/fx)25/574 (82%)30/56 (7%)35/510 (11%)CH Cycles5 or fewer5 (6%)6-851 (56%)9-129 (10%)12 or more25 (28%)CH AgentsFOLFOX/mFOLFOX79 (88%)CAPOX7 (8%)Other4 (4%) Open table in a new tab

Invitro and invivo studies on the association of long non‑coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5‑fluorouracil in rectal cancer.

There is no predictive biomarker for response to 5‑fluorouracil (5FU)‑based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non‑coding RNAs (lncRNAs) linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU‑susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17cases, whereas the ratios were high in 14cases; 11 of the 17cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU‑based NAC in rectal cancer.

Novel Description of Nash's Rectal Funnel for Drainage of Pelvic Collections Following Colorectal Surgery

A 50-year-old gentleman whilst undergoing neoadjuvant chemotherapy for rectal cancer underwent an emergency Hartman’s procedure for a stercoral perforated rectosigmoid colon. One week post-operatively the patient became persistently pyrexial with rising inflammatory markers, two days after the withdrawal of an abdominal 20 F drain. A CT abdomen and pelvis with contrast showed a 6 × 7.5 × 6 cm presacral fluid collection.

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

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.

Short-course radiotherapy followed by neo-adjuvant chemotherapy in rectal cancer with synchronous liver metastases: A single institution experience

Short-course radiotherapy followed by neo-adjuvant chemotherapy in rectal cancer with synchronous liver metastases: A single institution experience

Pathological complete response after neoadjuvant chemotherapy for rectal cancer with synchronous multiple liver metastases: a report of an unusual case.

BackgroundSystemic chemotherapy for stage IV colorectal cancer has advanced markedly in the recent years. We report an unusual case of 13 synchronous liver metastases for which a pathological complete response was achieved with neoadjuvant chemotherapy (NAC) consisting of a combination of 5-fluorouracil (5-FU), oxaliplatin, leucovorin (mFOLFOX6), and bevacizumab.Case presentationA 44-year-old man was diagnosed with colorectal cancer with synchronous liver metastases. We resected the primary rectal tumor first. Further, after providing NAC for hepatic metastases, lateral segmentectomy and partial resection of the liver were performed. The subsequent result was compatible with a complete pathological response. The postoperative course was uneventful, and the patient is currently alive 5 years after the first surgery without evidence of recurrence and without adjuvant chemotherapy.ConclusionsFor patients with initially resectable colorectal liver metastases, the survival benefits of NAC are still unclear. We report a rare case of 13 synchronous liver metastatic lesions from rectal cancer with a complete pathological response after neoadjuvant bevacizumab-containing chemotherapy.

Extending neoadjuvant chemotherapy in rectal cancer

Lancet Oncology, The - In Press.Proof corrected by the author Available online since jeudi 16 juillet 2015

Surgical management of patients with pathologic complete response in the primary tumor after neoadjuvant chemotherapy for rectal cancer

To summarize and analyze the clinicopathological features and surgical management of patients with pathologic complete response (pCR) in the primary tumor after neoadjuvant chemotherapy for rectal cancer, and to explore the rational treatment of this entity. Clinical data of fifty-two patients with locally advanced mid-low rectal cancer admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Sciences from January 1994 to December 2013 were retrospectively analyzed. They were treated with neoadjuvant chemotherapy and achieved pathological complete response in the primary tumor. The preoperative clinical staging were stage II (cT3~4N0) in 10 cases and stage III (cT3~4N+) in 42 cases. After the neoadjuvant therapy, 10 cases achieved clinical complete response (cCR) (19.2%). Radical surgery was performed in 51 patients. Among them, five patients (9.8%) had pathological lymph node metastasis. One cCR patient underwent transanal local excision. The postoperative complication rate was 21.2%. During a median follow-up of 23.6 months, only one patient developed bone metastasis and another one had enlarged mesenteric and retroperitoneal lymph nodes detected by imaging. All the patients were alive by the last follow-up. The 2-year disease-free survival rate was 96.2% and overall survival rate was 100%. Radical surgery remains the standard therapy for cCR patients with rectal cancer after neoadjuvant chemotherapy. Local excision and "wait and see" should be recommended with great caution and limited to patients who cannot tolerate or refuse radical surgery with a strong demanding for sphincter saving, or applied in clinical trials.

Role of bevacizumab in neoadjuvant chemotherapy and its influence on microvessel density in rectal cancer.

The role of bevacizumab (Bev) in neoadjuvant chemotherapy (NAC) without radiotherapy for rectal cancer has not been fully discussed. The purpose of this study is to assess the clinicopathological benefit of Bev in NAC for rectal cancer and to investigate its influence on microvessel status in cancerous tissue. Data on 47 patients with rectal cancer, who received NAC with or without Bev between August 2008 and November 2012, were analyzed retrospectively. The objective response was evaluated using the maximum tumor diameter. Tumor regression grade 3/4 was classified as a pathological response. Thirty-one patients (66 %) received NAC that included Bev and the other 16 patients were treated without Bev. The objective response rate was significantly higher in the Bev group than in the non-Bev group (64.5 vs. 25.0 %, p = 0.015). The rate of pathological response was much higher in the Bev group (41.9 %) than in the non-Bev group (12.5 %), but did not reach significant difference (p = 0.052). Microvessel density (MVD) in the resected cancerous tissue was significantly lower in the Bev group than in the non-Bev group. We have confirmed that objective and pathological responses were better in patients treated with NAC that included Bev than in those who received NAC without Bev. Additionally, MVD in tumor tissues was inhibited in the patients treated with Bev. To investigate the impact of Bev in NAC on long-term survival, further follow-up is required.

A clinical parameters-based predictive model to predict early efficacy for rectal cancer patients with neoadjuvant chemotherapy alone: Subgroup efficacy analysis of a phase II study.

716 Background: To avoid the damage of radiotherapy for a part of patients, we have an ongoing phase II study comparing Neoadjuvant FOLFOX6 chemotherapy with or without radiation in Rectal Cancer. To define the population who could obtain benefit from neoadjuvant chemotherapy alone, we aimed to develop a model in which clinical parameters are used to predict early efficacy of neoadjuvant chemotherapy for rectal cancer, including tumor regression grade (TRG) and ypTNM down-staging. Methods: Until now, 116 patients were enrolled into FOLFOX6 chemotherapy alone group. All the clinical parameters were collected, including gender, age, tumor location and size by MRI imaging, blood routine test, blood biochemistry and serum tumor markers, TRG and ypTNM staging. 96 patients were used to be training set and another 20 patients was the validation set. Binary logistic regression was used to analyze the effect of all clinical factors on TRG and ypTNM stage. Clinical variables were incorporated into the Cox models for multivariate analysis. Results: Among the 116 patients, 9 patients had TRG 0 (complete regression), 26 patients with TRG 1 and 81 patients with TRG 2 to 3 (poor regression). 47 (40.5%) patients had good down-staging with ypTNM stage 0 and stage I. The optimal multivariable predictive model for TRG (0-1 vs. 2-3) was a four-variable model consisting of age, ApoA1, tumor length and tumor encircle size (AUC=0.732, 95% CI, 0.614–0.849). The model for ypTNM (stage 0-I vs. II-III) was also the four parameters (AUC=0.725, 95% CI, 0.615–0.835). Patients with younger age, shorter tumor length, smaller encircle size and higher ApoA1 had better outcome with chemotherapy. Applying the four clinical parameters model to the validation cohort, a good performance (AUC=0.792, 95% CI, 50.54–0.95) was obtained. Conclusions: With this predictive model, the patients who might obtain good efficacy from neoadjuvant FOLFOX6 chemotherapy could avoid radiotherapy damage. And better suggestion would be provided for patients who might be high risk with chemotherapy alone.

The emerging role of neoadjuvant chemotherapy for rectal cancer.

Locally advanced rectal cancer remains a substantial public health problem. Historically, the disease has been plagued by high rates of both distant and local recurrences. The standardization of pre-operative chemoradiation and transmesorectal excision (TME) have greatly lowered the rates of local recurrence. Efforts to improve treatment through use of more effective radiosensitizing therapies have proven unsuccessful in rectal cancer. Presently, due to improved local therapies, distal recurrences represent the dominant problem in this disease. Adjuvant chemotherapy is currently of established benefit in colorectal cancer. As such, adjuvant chemotherapy, consisting of fluoropyrimidine and oxaliplatin, represent the standard of care for many patients. However, after pre-operative chemoradiotherapy and rectal surgery, the administration of highly effective chemotherapy regimens has proven difficult. For this reason, novel neoadjuvant approaches represent appealing avenues for investigation. Strategies of neoadjuvant chemotherapy alone, neoadjuvant chemotherapy followed by chemoradiation and neoadjuvant chemoradiation followed by chemotherapy are under investigation. Initial encouraging results have been noted, though definitive phase III data is lacking.

Predictors of treatment interruption/dose reduction of neoadjuvant chemotherapy for rectal cancer: A multicenter study.

580 Background: Neoadjuvant chemoradiation (CRT) is the standard of care for patients with locally advanced rectal cancer. Many patients require dose reduction or chemotherapy interruption due to significant toxicities. To assess the predictors of neoadjuvant chemotherapy treatment (tx) adjustments, we performed a retrospective study in four Canadian provinces. Methods: Cancer Registries identified consecutive patients with clinical stage I-III rectal cancer from the Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and the Dr. H. Bliss Murphy Cancer Centre who received CRT and had curative intent surgery (Sx) from 2005 to 2012. Patient, tumor and tx characteristics were correlated with treatment completion. Results: Of the 891 patients included, 886 patients had tx dose adjustments data available. 738 (83.2%) completed the planned neoadjuvant chemotherapy, while 148 (16.7%) failed to complete planned chemotherapy. Patients who required tx interruption/cessation or dose reduction were more likely to be female, elderly, had higher ECOG PS and were treated with fluorouracil (FU) chemotherapy in univariate analysis (see Table). On multivariable analysis, female gender (OR 1.807, 95% CI 1.02-3.2, p=0.042) and tx with FU (vs capecitabine) (OR 2.7, 95% CI 1.52-4.77, p=0.0007) were associated with dose reduction and tx interruption/cessation. Conclusions: Gender and type of chemotherapy are predictors of neoadjuvant chemotherapy interruption or dose reduction in rectal cancer. Careful monitoring of these patients is warranted during neoadjuvant CRT. [Table: see text]