Recurrence In Rectal Cancer Patients Research Articles

Outcomes of chemotherapy/chemoradiation vs. R2 surgical debulking vs. palliative care in nonresectable locally recurrent rectal cancer.

Locally recurrent rectal cancer is resected with clear margins in only 50% of cases, and these patients achieve a three-year survival rate of 50%. Outcomes and therapeutic strategies for nonresectable locally recurrent rectal cancer have been much less explored. The aim of the study was to assess the three-year progression-free survival and the three-year overall survival in locally recurrent rectal cancer patients treated by chemotherapy/chemoradiation only vs. chemotherapy/chemoradiation and R2 surgical debulking vs. palliative care. A total of 86 patients affected by nonresectable locally recurrent rectal cancer were included: three-year progression-free survival was 15.8% with chemotherapy/chemoradiation vs. 20.3% with R2 surgical debulking (Log-rank p=0.567), but both rates were higher than best palliative care (0.0%, Log-rank p=0.0004). Three-year overall survival rates were respectively 62.0%, 70.8% and 0.0% (Log-rank p<0.0001). Chemotherapy/chemoradiation (HR 0.33, p=0.028) and R2 surgical debulking with or without chemotherapy/chemoradiation (HR 0.23, p=0.005) were independent predictors of improved progression-free survival on multivariate analysis. In conclusion, both chemotherapy/chemoradiation alone and R2 surgery with or without chemotherapy/chemoradiation provide a survival benefit over palliative care in nonresectable locally recurrent rectal cancer. However, considering that pelvic debulking is burdened by a high rate of complications, and considering its negligible impact on progression-free survival and overall survival when associated to medical therapy, surgery should be avoided in this setting.

Proton beam reirradiation for locally recurrent rectal cancer patients with prior pelvic irradiation.

The aim of the present study was to report the feasibility of proton beam reirradiation for patients with locally recurrent rectal cancer (LRRC) with prior pelvic irradiation. The study population included patients who were treated with proton beam therapy (PBT) for LRRC between 2008 and December 2019 in our institution. Those who had a history of distant metastases of LRRC, with or without treatment, before reirradiation, were excluded. Overall survival (OS), progression-free survival (PFS) and local control (LC) were estimated using the Kaplan-Meier method. Ten patients were included in the present study. The median follow-up period was 28.7months, and the median total dose of prior radiotherapy (RT) was 50Gy (range, 30Gy-74.8Gy). The median time from prior RT to reirradiation was 31.5months (range, 8.1-96.6months), and the median reirradiation dose was 72Gy (relative biological effectiveness) (range, 56-77Gy). The 1-year/2-year OS, PFS and LC rates were 100%/60.0%, 20.0%/10.0% and 70.0%/58.3%, respectively, with a median survival time of 26.0months. Seven patients developed a Grade 1 acute radiation dermatitis, and no Grade≥2 acute toxicity was recorded. Grade≥3 late toxicity was recorded in only one patient, who had developed a colostomy due to radiation-related intestinal bleeding. Reirradiation using PBT for LRRC patients who had previously undergone pelvic irradiation was feasible. However, the indications for PBT reirradiation for LRRC patients need to be considered carefully due to the risk of severe late GI toxicity.

Machine Learning Based Prediction of Distant Metastasis in Rectal Cancer Patients with Complete Response following Neoadjuvant Chemoradiotherapy

Distant metastasis (DM) is the leading cause of disease recurrence in rectal cancer patients with clinical or pathological complete response (CR) following neoadjuvant chemoradiotherapy (nCRT). Identifying these patients may help to tailor the treatment approach. The aim of this study was to predict the rectal cancer patients with high risk of DM following CR with nCRT, using machine learning (ML), based on patient, disease and treatment related clinical factors. Data of the rectal cancer patients treated with nCRT at three academic centers between 2010-2022 were collected. Patients with secondary malignancies were excluded. 157 patients with CR were included in the analysis. Median age was 63 (31-85). Female/male ratio was 59/98. Tumor location was proximal-, mid- and distal-rectum in 9, 65 and 83 patients, respectively. cT stage was T2, T3 and T4 in 14, 120 and 23 patients, respectively. 122 patients had cN (+). Median tumor and regional lymph nodes doses were 50.4 (45-56) Gy and 45 (45-50.4) Gy, respectively, in 25-28 fractions, concurrently with capecitabine. 63 patients had clinical CR and were followed up without surgery, and 94 had pathological CR. Median RT-surgery interval was 11 (3.4-59) weeks. 41 patients were managed with total neoadjuvant treatment and 52 received adjuvant systemic treatment. Median follow up time was 37 (3-143) months. DM was detected in 18 patients at median 14 (2-87) months and local tumor recurrence/progression was seen in 9. A ML model was used to predict DM based on patient, disease and treatment related 37 clinical factors. Statistical analysis was conducted using Python (v.3.7). P<0.05 was accepted as statistically significant. Multiple Linear Regression was used to analyze the relationship between DM and independent continuous variables. Chi-square test was used to analyze the difference between the observed frequency distribution of a categorical variable and the expected frequency distribution. Confusion matrix algorithm was used to evaluate the performance of the model. Logistic regression algorithm (LRA) was selected as the best performing algorithm for the ML model that used 37 variables from 157 patients. The model was trained using 75% of the data and the remaining 25% was used for testing. CEA, ratio of post- to pre-RT tumor SUVmax, tumor dose, RT-surgery interval, pre-RT weight loss, smoking history, cN status, and gender were significant parameters to predict DM, based on the LRA of the ML model. Accuracy score of the model was 92% and AUC of the ROC was 74%. Precision (positive predictive value) and recall (sensitivity) of the model were 67% and 50%, respectively. Machine learning has a high rate of correctly classifying patients and good performance in predicting those with DM. Further studies with larger patient numbers are needed.

A Deep Learning Framework with Explainability for the Prediction of Lateral Locoregional Recurrences in Rectal Cancer Patients with Suspicious Lateral Lymph Nodes.

Malignant lateral lymph nodes (LLNs) in low, locally advanced rectal cancer can cause (ipsi-lateral) local recurrences ((L)LR). Accurate identification is, therefore, essential. This study explored LLN features to create an artificial intelligence prediction model, estimating the risk of (L)LR. This retrospective multicentre cohort study examined 196 patients diagnosed with rectal cancer between 2008 and 2020 from three tertiary centres in the Netherlands. Primary and restaging T2W magnetic resonance imaging and clinical features were used. Visible LLNs were segmented and used for a multi-channel convolutional neural network. A deep learning model was developed and trained for the prediction of (L)LR according to malignant LLNs. Combined imaging and clinical features resulted in AUCs of 0.78 and 0.80 for LR and LLR, respectively. The sensitivity and specificity were 85.7% and 67.6%, respectively. Class activation map explainability methods were applied and consistently identified the same high-risk regions with structural similarity indices ranging from 0.772-0.930. This model resulted in good predictive value for (L)LR rates and can form the basis of future auto-segmentation programs to assist in the identification of high-risk patients and the development of risk stratification models.

Implementation of an Enhanced Recovery after Surgery Protocol in Advanced and Recurrent Rectal Cancer Patients after beyond Total Mesorectal Excision Surgery: A Feasibility Study.

The implementation of an Enhanced Recovery After Surgery (ERAS) protocol in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) has been deemed unfeasible until now because of the heterogeneity of this disease and low caseloads. Since evidence and experience with ERAS principles in colorectal cancer care are increasing, a modified ERAS protocol for this specific group has been developed. The aim of this study is to evaluate the implementation of a tailored ERAS protocol for patients with LARC or LRRC, requiring beyond total mesorectal excision (bTME) surgery. Patients who underwent a bTME for LARC or LRRC between October 2021 and December 2022 were prospectively studied. All patients were treated in accordance with the ERAS LARRC protocol, which consisted of 39 ERAS care elements specifically developed for patients with LARC and LRRC. One of the most important adaptations of this protocol was the anaesthesia procedure, which involved the use of total intravenous anaesthesia with intravenous (iv) lidocaine, iv methadone, and iv ketamine instead of epidural anaesthesia. The outcomes showed compliance with ERAS care elements, complications, length of stay, and functional recovery. A follow-up was performed at 30 and 90 days post-surgery. Seventy-two patients were selected, all of whom underwent bTME for either LARC (54.2%) or LRRC (45.8%). Total compliance with the adjusted ERAS protocol was 73.6%. Major complications were present in 12 patients (16.7%), and the median length of hospital stay was 9 days (IQR 6.0-14.0). Patients who received multimodal anaesthesia (75.0%) stayed in the hospital for a median of 7.0 days (IQR 6.8-15.5). These patients received fewer opioids on the first three postoperative days than patients who received epidural analgesia (p < 0.001). The implementation of the ERAS LARRC protocol seemed successful according to its compliance rate of >70%. Its complication rate was substantially reduced in comparison with the literature. Multimodal anaesthesia is feasible in beyond TME surgery with promising effects on recovery after surgery.

Prognostic Impact of Ras Mutation on Surgical Strategy in Rectal Cancer Patients Undergoing Neoadjuvant Treatment.

Complete clinical response in rectal cancer after neoadjuvant chemo-radiotherapy is challenging. Indeed, indication to surgery vs. "watch and wait" is a debate due the poor predictive value of restaging exams in order to identify a pathological complete response (pCR). Improving the knowledge on mutational pathways such as MAPK/ERK could be helpful in assessing the real impact of disease on prognosis and in choosing the best therapeutic target. This study aimed to evaluate the significance of biomolecular parameters as prognostic factors in patients undergoing radical surgery after chemo-radiotherapy. A retrospective analysis was performed including 39 patients who had undergone radical surgery after neoadjuvant chemo-radiotherapy for rectal adenocarcinoma stage II-III through additional evaluation of the following biomolecular markers on surgical specimens: exons 2, 3 and 4 of the KRAS and NRAS genes and exon 15 of BRAF by pyrosequencing. Kaplan-Meier survival curves were plotted to evaluate the association of pathologic response and RAS status with progression-free survival (PFS) and overall survival (OS). The log-rank test was used to assess statistical differences among the survival curves. Data analysis showed RAS mutation in 15 patients (38.46%). pCR was achieved in seven patients (18%), including only two RAS mutation cases. The distribution of evaluated variables was homogeneous in the two groups based on pathological response. The Kaplan-Meier curve showed poor outcomes in OS and PFS in patients with RAS mutation (p=0.0022 and p=0.000392, respectively), but no significant differences based on pathological response for both OS and PFS. RAS mutation seems to be related to poor prognosis and increased risk of recurrence in rectal cancer patients undergoing radical surgery after chemo-radiotherapy.

Bayesian network structure for predicting local tumor recurrence in rectal cancer patients treated with neoadjuvant chemoradiation followed by surgery.

Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assist caregivers with patient management. However, some concerns are associated with the standard approaches to developing these structures in medicine. Therefore, this study aims to compare Bayesian network structures that stem from these two techniques. A retrospective analysis was performed on 6754 locally advanced rectal cancer (LARC) patients enrolled in 14 international clinical trials. Local tumor recurrence at 2, 3, and 5-years was defined as the endpoints of interest. Five rectal cancer treating physicians from three countries elicited the expert structure. The algorithmic structure was inferred from the data with the hill-climbing algorithm. Structural performance was assessed with calibration plots and area under the curve values. The area under the curve for the expert structure on the training and validation data was above 0.9 and 0.8, respectively, for all the time points. However, the algorithmic structure had superior predictive performance over the expert structure for all time points of interest. We have developed and internally validated a Bayesian networks structure from experts' opinions, which can predict the risk of a LARC patient developing a tumor recurrence at 2, 3, and 5years. Our result shows that the algorithmic-based structures are more performant and less interpretable than expert-based structures.

Oncological outcomes and Quality of life in Locally Advanced and Recurrent Rectal cancer patients following Pelvic Exenteration

Background: Pelvic exenteration remains the standard treatment option for locally advanced and recurrent rectal cancer, although it is a complex surgical procedure associated with morbidity. This review aims to look at short term and long term surgical outcomes, oncological outcomes, and quality of life after pelvic exenteration

Cost-Effectiveness of TME Alone vs. Neoadjuvant Chemoradiotherapy for Stage II and III Rectal Cancer

<h3>Purpose/Objective(s)</h3> The role of neoadjuvant chemoradiotherapy in rectal cancer is rapidly evolving. Neoadjuvant chemoradiotherapy (nCRT) reduces the risk of local recurrence in rectal cancer patients, but is associated with increased adverse events, costs, and prolonged treatment time. Pre-operative risk stratification of patients into low- and high-risk categories for local recurrence may identify populations that benefit from nCRT, despite these additional costs. Although total mesorectal excision (TME) alone and nCRT with TME (nCRT/TME) are both in clinical practice, no cost-effectiveness analysis comparing these two treatment approaches in rectal cancer has been published. We sought to determine the cost-effectiveness of primary TME versus nCRT with TME for patients with rectal cancer. <h3>Materials/Methods</h3> We developed a Markov model to simulate the 3-year outcomes of 1 million hypothetical patients as treated on the OCUM trial (NCT 325649) with histologically confirmed invasive carcinoma of the rectum (cT2 to cT4, mC0) with distal tumor margin less than 16 cm from the anal verge undergoing either primary TME or nCRT followed by TME. To calculate the incremental cost-effectiveness ratios, we used utilities and probabilities from the literature and costs from Medicare fee schedules and the Healthcare Bluebook. We discounted utilities and costs at 3% annually. Willingness to pay (WTP) was defined at ICER of $100 000 or less per quality-adjusted life-year (QALY). 1-way sensitivity analyses were performed varying selective model inputs to account for uncertainty. Probabilistic sensitivity analysis (PSA) was conducted. <h3>Results</h3> TME was the dominant strategy compared with nCRT and TME (incremental cost-effectiveness ratio, -$158,201.86/QALY). TME and nCRT/TME were associated with costs of $32,518 and $70,583 and QALYs of 1.91 and 1.67, respectively. TME remained the dominant strategy across all 1-way sensitivity analyses in cost, utility states, and probabilities with the exception of the utilities of the health states post-TME and post-nCRT/TME. When the utility of TME treatment fell below 0.4, nCRT/TME became the dominant strategy. Conversely, when the utility of nCRT/TME treatment rose above 0.69 (.1 above the baseline TME utility), nCRT/TME became the dominant strategy. PSA with 1,000,000 samples revealed TME was the cost-effective strategy in 67.4% of trials. <h3>Conclusion</h3> In patients with rectal cancer, TME was the cost-effective strategy compared with nCRT/TME. TME remained the cost-effective strategy across a range of tested variations in cost, probabilities, and utilities but was sensitive to the utility of TME and nCRT/TME. The results of this study contribute to the growing body of literature decreasing usage of nCRT/TME for patients with rectal cancer, particularly if they have low risk of local recurrence.

Predictive factors for distant recurrence of colorectal cancer in patients after curative resection for stage I-III colorectal cancer in Australia.

Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery. All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer. A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50years of age having the best overall 5-year survival. Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features.

Re-Irradiation in Patients with Recurrent Rectal Cancer is Safe and Feasible

BackgroundThere is no consensus yet for the best treatment regimen in patients with recurrent rectal cancer (RRC). This study aims to evaluate toxicity and oncological outcomes after re-irradiation in patients with RRC in our center. Clinical (cCR) and pathological complete response (pCR) rates and radicality were also studied.MethodsBetween January 2010 and December 2018, 61 locally advanced RRC patients were treated and analyzed retrospectively. Patients received radiotherapy at a dose of 30.0–30.6 Gy (reCRT) or 50.0–50.4 Gy chemoradiotherapy (CRT) in cases of no prior irradiation because of low-risk primary rectal cancer. In both groups, patients received capecitabine concomitantly.ResultsIn total, 60 patients received the prescribed neoadjuvant (chemo)radiotherapy followed by surgery, 35 patients (58.3%) in the reRCT group and 25 patients (41.7%) in the long-course CRT group. There were no significant differences in overall survival (p = 0.82), disease-free survival (p = 0.63), and local recurrence-free survival (p = 0.17) between the groups. Patients in the long-course CRT group reported more skin toxicity after radiotherapy (p = 0.040). No differences were observed in late toxicity. In the long-course CRT group, a significantly higher cCR rate was observed (p = 0.029); however, there was no difference in the pCR rate (p = 0.66).ConclusionsThe treatment of RRC patients with re-irradiation is comparable to treatment with long-course CRT regarding toxicity and oncological outcomes. In the reCRT group, less cCR was observed, although there was no difference in pCR. The findings in this study suggest that it is safe and feasible to re-irradiate RRC patients.

Clinical selection strategy for and evaluation of intra-operative brachytherapy in patients with locally advanced and recurrent rectal cancer

Background and purposeA radical resection of locally advanced rectal cancer (LARC) or recurrent rectal cancer (RRC) can be challenging. In case of increased risk of an R1 resection, intra-operative brachytherapy (IOBT) can be applied. We evaluated the clinical selection strategy for IOBT. Materials and methodsBetween February 2007 and May 2018, 132 LARC/RRC patients who were scheduled for surgery with IOBT standby, were evaluated. By intra-operative inspection of the resection margin and MR imaging, it was determined whether a resection was presumed to be radical. Frozen sections were taken on indication. In case of a suspected R1 resection, IOBT (1 × 10 Gy) was applied. Histopathologic evaluation, treatment and toxicity data were collected from medical records. ResultsTumour was resected in 122 patients. IOBT was given in 42 patients of whom 54.8% (n = 23) had a histopathologically proven R1 resection. Of the 76 IOBT-omitted R0 resected patients, 17.1% (n = 13) had a histopathologically proven R1 resection. In 4 IOBT-omitted patients, a clinical R1/2 resection was seen. In total, correct clinical judgement occurred in 72.6% (n = 88) of patients. In LARC, 58.3% (n = 14) of patients were overtreated (R0, with IOBT) and 10.9% (n = 5) were undertreated (R1, without IOBT). In RRC, 26.5% (n = 9) of patients were undertreated. ConclusionIn total, correct clinical judgement occurred in 72.6% (n = 88). However, in 26.5% (n = 9) RRC patients, IOBT was unjustifiedly omitted. IOBT is accompanied by comparable and acceptable toxicity. Therefore, we recommend IOBT to all RRC patients at risk of an R1 resection as their salvage treatment.

Recurrence hazard of rectal cancer compared with colon cancer by adjuvant chemotherapy status: a nationwide study in Japan.

Previous studies of stage III colon cancer using the hazard function demonstrated that the risk of recurrence in patients with adjuvant chemotherapy never exceeded that of patients without adjuvant chemotherapy. However, it is unclear whether the same can be said for rectal cancer patients and whether adjuvant chemotherapy reduces recurrence. This study aimed to compare the recurrence hazard of stage III rectal cancer with that of colon cancer by adjuvant chemotherapy status using the hazard function, a method that allows for the assessment of instantaneous risk of recurrence over time. This retrospective nationwide study consisted of 10,356 patients with stage III colorectal cancer who underwent curative resection between January 1997 and December 2012 in Japan. Recurrence hazards of rectal and colon cancers were compared between patients treated with adjuvant chemotherapy and those who were not. Analyses in which recurrence was divided into local and distant recurrence were also performed. The hazard rate of recurrence in rectal cancer patients with adjuvant chemotherapy was consistently lower throughout the follow-up period, and the peak time of recurrence later, compared to patients without adjuvant chemotherapy (peaked at 15.7 vs. 7.1months). Adjuvant chemotherapy also strongly suppressed distant recurrence but not local recurrence in rectal cancer patients. Similar results were observed in colon cancer patients. Our results using nationwide real-world data in Japan suggest that, similar to what is observed in colon cancer patients, adjuvant chemotherapy delays the peak of recurrence and suppresses distant recurrence in stage III rectal cancer patients.

OC-0100: A Bayesian network structure for predicting local recurrence in rectal cancer patients

OC-0100: A Bayesian network structure for predicting local recurrence in rectal cancer patients

The role of carbon ion radiotherapy for unresectable locally recurrent rectal cancer: a single institutional experience

BackgroundTreatment for locally recurrent rectal cancer after surgery is still a challenge. With the physical and biological advantages, carbon-ion radiotherapy (CIRT) could be a choice for these patients. The purpose of this study was to investigate the efficacy and safety of CIRT for unresectable locally recurrent rectal cancer in Chinese patients.MethodsDate from 25 patients with unresectable locally recurrent rectal cancer treated by CIRT from July 2015 to April 2019 were analyzed retrospectively. The endpoints of this study were overall survival (OS), local control (LC) and acute and late toxicity.ResultsWith the median follow-up of 19.6 (range 5.1–52.5) months, data of all 25 patients were collected. Median prescribed dose for tumor was 72Gy (relative biologic efficacy (RBE)) (range 48–75.6Gy (RBE)). The LC rates at 1 and 2 years were 90.4 and 71.8%. Overall LC at 1- and 2-year were 76.2 and 30.5% for 9 patients whose prescribed tumor doses of CIRT< 66 Gy (RBE), 100 and 100% for 16 patients whose prescribed doses of CIRT≥66 Gy (RBE). Patients received ≥66 Gy (RBE) had obviously better LC rates than those received < 66 Gy (RBE) (P = 0.001). The OS rates at 1 and 2 years were 82.9 and 65.1%, respectively. No acute toxicity over grade 2 was observed, grade 3 late toxicity were observed in 3 patients: gastrointestinal toxicity (n = 1), neuropathy (n = 1), pelvic infection (n = 1). No Grade 4 or higher toxicity was observed.ConclusionOur study shows that CIRT is effective for unresectable locally recurrent rectal cancer patients with acceptable toxicity.

First Clinical Results of Image-Guided Navigation in Locally Advanced Primary and Recurrent Rectal Cancer Patients

First Clinical Results of Image-Guided Navigation in Locally Advanced Primary and Recurrent Rectal Cancer Patients

545P - Feasibility of chemoradiotherapy in rectal cancer patients with peritumoral abscesses and fistulas: A case-control non-inferiority trial

BackgroundNeoadjuvant chemoradiotherapy (CRT) is a standard treatment for patients with locally advanced rectal cancer and is effective as a palliative care in patients with nonresectable tumors. Unfortunately CRT is often being withheld for patients with tumor-associated complications due to safety concerns. Literature search reveals only case reports and neither supports nor declines additional risks of CRT in this patient group. The aim of this study was to determine feasibility of CRT in rectal cancer with peritumoral abscesses and fistulas. MethodsPatients with locally advanced or recurrent rectal cancer with peritumoral abscesses and fistulas were included in the study group. The control group consisted of T4 locally advanced or recurrent rectal cancer patients without complications, both groups received long-course neoadjuvant CRT. Groups were matched by age, previous treatment, treatment year. The primary endpoint was CRT toxicity. Secondary endpoints included postoperative morbidity (Clavien-Dindo), pathologic complete response (pCR) and 2year PFS. Results30 patients were included in each group. Patients in the main group had following tumor-associated complications: perianal fistula (n=11), abdominal wall fistula (n=1), rectovaginal fistula (n=9), rectovesical fistula (n=4), peritumoral abscess (n=17). Grade 3-4 toxicity was observed in 2 (6.66%) vs 3 (10%) patients, non-inferiority was confirmed (p=0.0326). Grade 3-4 postoperative complications were observed in 2 (7.14%) patients in the main group and in 3 (10.7%) patients in the control group (p=0.639) with no cases of mortality. pCR was achieved in 2 (7.14%) and 5 (17.8%) patients accordingly (p=0.225). Median follow-up was 25.2 months in the main group and 27.4 months in the control group. Two-year OS was 69% vs 100% (p=0.11), 2-year PFS was 65% vs 78% (p=0.434). ConclusionsPeritumoral abscesses and fistulas should not be considered as contraindication to neoadjuvant chemoradiotherapy. CRT is feasible and safe in patients with tumor-associated complications. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

MRI-based EMVI positivity predicts systemic recurrence in rectal cancer patients with a good tumor response to chemoradiotherapy followed by surgery.

This study aimed to determine the prognostic value of baseline magnetic resonance imaging-based extramural vascular invasion status (EMVI) among rectal cancer patients with a good tumor response to standard chemoradiotherapy followed by surgery. A total of 359 patients with ypT0-2/N0 disease from The Yonsei Multicenter Colorectal Cancer Electronic Database were retrospectively included between January 2000 and December 2014. Magnetic resonance images and medical records were reviewed to investigate risk factors for tumor recurrence. When we compared patients without and with EMVI, significant differences were observed in the 5-year disease-free survival rate (DFS) (80.8% vs 57.8%, P = 0.005) and in the 5-year systemic recurrence-free survival rate (SRFS) (86.9% vs 64.3%, P = 0.007). In the multivariate analysis, both mrEMVI and APR independently predicted overall DFS (APR; HR 2.088, 95% CI: 1.082-4.031, P = 0.028, mrEMVI; HR: 2.729, 95% CI: 1.230-6.058, P = 0.014). mrEMVI was only independent prognostic factor for systemic recurrence with statistical significance (HR: 3.321, 95% CI: 1.185-9.309, P = 0.022). Even in rectal cancer patients with a good response to chemoradiotherapy followed by curative surgery, extramural vascular invasion and APR may predict poor disease-free survival outcomes. Intensified treatment strategy should be considered.

Effect and safety of proton beam therapy for locally recurrent rectal cancer.

743 Background: The first choice of treatment for locally recurrent rectal cancer is surgical resection. However, the operation is often difficult with high perioperative risk. For surgically unfit cases, proton beam therapy (PBT) is proposed as the treatment option. However, its efficacy for locally recurrent rectal cancer remains unclear. Therefore, this study aimed to evaluate the efficacy and safety of PBT for locally recurrent rectal cancer. Methods: A total of 23 patients with locally recurrent rectal cancer who received PBT were retrospectively evaluated, from November 2005 to July 2014. Patients with single lesion, who refuse the radical surgical therapy, or who were considered unfit for the operation were included in this study. All patients were treated with 2.8Gy relative biological effectiveness (RBE)/fraction. Twenty-five irradiations were performed, with a total irradiation of 70Gy RBE. Unfit for operation criteria include invasion to the vertebra higher than the third sacrum or lateral lymph node recurrence after a lateral lymph node dissection. To assess the safety of PBT, adverse events were evaluated by using the Common Terminology Criteria for Adverse Effects (CTCAE version4.0). To assess the efficacy, the overall and relapse-free survival rates and local control rate were evaluated. Results: Sixteen patients were unfit for operation, and seven refused surgery. Three patients experienced Grade 3 late adverse events in the CTCAE (two ileum fistula and one urinary tract obstruction). The median follow-up time was 28.9 months. The 5-year overall and relapse-free survival rates were 47.6% and 20.2%, respectively. Fifteen patients (65.2%) showed distant metastasis or regrowth at the locally recurrent site. The 5-year local control rate was 39.0%. Ten patients (43.4%) showed regrowth at the proton beam irradiation site. Conclusions: PBT was relatively effective for locally recurrent rectal cancer with manageable adverse effects. Therefore, PBT may be considered as the therapeutic option for selected locally recurrent rectal cancer patients.

CT guidance 125I seed implantation for pelvic recurrent rectal cancer assisted by 3D printing individual non-coplanar template

Objective: To analyze the difference of dosimetric parameters between pre-plan and post-plan of 125I radioactive seed implantation assisted by 3D printing individual non-coplanar template (3D printing template) for locally recurrent rectal cancer (LRRC). Methods: From February 2016 to April 2016, a total of 10 patients with locally recurrent rectal cancer received 125I seeds implantation under CT guidance assisted by 3D printing template in Department of Radiation Oncology, Peking University Third Hospital.Each patient underwent CT simulation, three-dimentional treatment planning pre-implantation, 3D printing template design, radioactive seed implantation assisted by 3D printing template and dosimetric verification post implantation. The median activity of seed was 0.63 mCi (0.58 to 0.7 mCi) (2.15- 2.59×107 Bq), and the median number of seeds was 80 (19 to 192). D90, D100, V100, V150, CI, EI, HI, D5cc, D2cc of bladder and bowel of pre-plan and post-plan were calculated, respectively.Paired t test was used to evaluate the difference of dosimetric parameters between pre-plan and post-plan. Results: The median D90 of pre-plan and post-plan were 13 761.0 and 12 798.8 cGy, respectively.The median D100 of pre-plan and post-plan were 5 293.6 and 5 397.9 cGy, respectively.The median V100 of pre-plan and post-plan were 90.0% and 90.0%, respectively.The median V150 of pre-plan and post-plan were 63.8% and 62.4%, respectively.The median CI of pre-plan and post-plan were 0.73 and 0.67.The median EI of pre-plan and post-plan were 0.22 and 0.30, respectively. The median HI of pre-plan and post-plan were 0.29 and 0.31.The median bladder D2cc of pre-plan and post-plan were 3 088.8 and 4 240.4 cGy, respectively.The median bowel D2cc of pre-plan and post-plan were 7 051.6 and 7 903.9 cGy, respectively. Conclusions: 3D printing template might be helpful for locally recurrent rectal cancer patients who received 125I radioactive seed implantation assisted by 3D printing individual template.Seed implantation might have more chances to achieve prescription dose and dose limitation of organs at risk of pre-plan, which is important for precise implantation and quality control.