Locally Recurrent Rectal Cancer Patients Research Articles

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.

Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts

BackgroundIn the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. MethodsPatients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. ResultsUse of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). ConclusionPrimary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

Factors associated with one-year mortality after curative surgery for primary clinical T4 and locally recurrent rectal cancer in elderly patients

IntroductionDespite advancements in colorectal cancer care, one-year post-operative mortality rates remain high for elderly patients who have undergone curative surgery for primary clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). This study aimed to identify factors associated with one-year mortality and to evaluate the causes of death. Materials & methodsThis retrospective cohort study included patients aged ≥70 years who underwent surgery with curative intent for cT4RC or LRRC between January 2013 and December 2020. Clinical and follow-up data were collected and analyzed to determine survival rates and investigate factors associated with mortality within one year after surgery. ResultsA total of 183 patients (94 cT4RC, 89 LRRC) were included. One-year mortality rates were 16.0% for cT4RC and 28.1% for LRRC (P = 0.064). In cT4RC patients, factors associated with one-year mortality were preoperative anemia (OR 3.83, P = 0.032), total pelvic exenteration (TPE) (OR 7.18, P = 0.018), multivisceral resections (OR 5.73, P = 0.028), pulmonary complications (OR 13.31, P < 0.001) and Clavien-Dindo grade ≥ III complications (OR 5.19, P = 0.025). In LRRC patients, factors associated with one-year mortality were TPE (OR 27.00, P = 0.008), the need for supported care after discharge (OR 3.93, P = 0.041) and Clavien-Dindo grade ≥ III complications (OR 3.95, P = 0.006). The main causes of death in cT4RC and LRRC patients were failure to recover (cT4RC 26.6%, LRRC 28.0%) and disease recurrence (cT4RC 26.6%, LRRC 60.0%). ConclusionIn order to tailor treatment in elderly with cT4RC and LRRC, factors associated with increased one-year mortality (e.g. pre-operative anemia, TPE) should be incorporated in the decision-making process. Clinical trial registrationNot applicable.

Post-operative complications following dose adaptation of intra-operative electron beam radiation therapy in locally advanced or recurrent rectal cancer.

The benefit of intra-operative radiotherapy (IORT) in the treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) lie in its ability to provide high-dose of radiation to limited at-risk volume, thereby eliminating microscopic disease and decreasing toxicity. A comparative study between high-dose-rate (HDR) brachytherapy, named intra-operative brachytherapy (IOBT), and intra-operative electron radiotherapy (IOERT) was performed showing favorable LRFS after IOBT, possibly due to a higher surface dose that is inherent in IOBT technique. The IOERT technique in Catharina Hospital Eindhoven was adapted to increase the surface dose, aiming to improve local control. Post-operative complications due to an increased radiation dose remain the matter of concern. This retrospective study was performed to compare complication rates before and after adapted IOERT dose. All patients undergoing surgery with IOERT for LARC or LRRC from September 2019 until July 2023, were considered. Patients selected until August 31, 2021 were included in control cohort (n = 108), and those chosen from September 1, 2021 onwards were included in intervention cohort (n = 92). Perioperative and (major) post-operative complications were classified retrospectively, during admission, at 30 days, and at 90 days. In LARC patients, a decrease in post-operative complications was observed (p = 0.009). 19% of LARC patients experienced major post-operative surgical complications, i.e., Clavien-Dindo grade 3b-5, regardless of treatment group. No difference in major 90-day complications was noted (p = 0.142). In LRRC patients, the use of induction chemotherapy decreased from 78% to 29% (p < 0.001), which complicated comparison. However, no difference in major post-operative complications was observed at 30 days (p = 0.222) or 90 days (p = 0.977) after surgery. Increased surface dose of IOERT does not seem to lead to an increase in post-operative complications. Further research is needed to evaluate the efficacy of dose adaptation in IOERT to improve local oncological control rates. Routine evaluation of CTCAE scores in follow-up will help uncover possible long-term radiation-induced toxicity.

Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)

IntroductionIn locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and...

Construction and validation of a prognostic nomogram for locally recurrent rectal cancer: a population-based study.

Postoperative recurrence was a life-threatening condition for patients with rectal cancer. Due to the heterogeneity of locally recurrent rectal cancer (LRRC) and controversy of the optimal treatment for patients, it was difficult to predict the prognosis of LRRC. This study aimed to develop and validate a nomogram that could accurately predict the survival probability of LRRC. Patients diagnosed with LRRC between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the analysis. Multiple imputations with chained equations were used for missing values. These patients were further randomized into training set and testing set. Cox regression was used for univariate and multivariate analysis. Potential predictors were screened by the least absolute shrinkage and selection operator (LASSO). The Cox hazards regression model was constructed and it was visualized by nomogram. C-index, calibration curve, and decision curve were used to evaluate the model's predictive ability. Then X-tile was used to calculate the optimal cut-off values for all patients and the cohort was divided into three groups. A total of 744 LRRC patients were enrolled and allocated to the training set (n=503) and the testing set (n=241). Cox regression analysis of the training set yielded meaningfully clinicopathological variables. A survival nomogram was created based on the identification of ten clinicopathological features in the LASSO regression analyses of the training set. The C-index of 3-, 5-year survival probabilities were 0.756, 0.747 in training set, and 0.719, 0.726 in testing set, respectively. The calibration curve and decision curve both demonstrated the satisfactory performance of the nomogram for prognosis prediction. Moreover, the prognosis of LRRC could be well distinguished according to the grouping of risk scores (P<0.001 in three groups). This nomogram was the first prediction model to preliminarily evaluate the survival of LRRC patients, which could provide more accurate and efficient treatment in clinical practice.

Locally recurrent rectal cancer and distant metastases: is there still a chance ofcure?

IntroductionPatients with locally recurrent rectal cancer (LRRC) generally have poor prognosis, especially those who have (a history of) distant metastases. The aim of this study was to investigate the impact of distant metastases on oncological outcomes in LRRC patients undergoing curative treatment. MethodsConsecutive patients with surgically treated LRRC between 2005 and 2019 in two tertiary referral hospitals were retrospectively analysed. Oncological survival of patients without distant metastases were compared with outcomes of patients with synchronous distant metastases with the primary tumour, patients with distant metastases in the primary-recurrence interval, and patients with synchronous LRRC distant metastases. ResultsA total of 535 LRRC patients were analysed, of whom 398 (74%) had no (history of) metastases, 22 (4%) had synchronous metastases with the primary tumour, 44 (8%) had metachronous metastases, and 71 (13%) had synchronous LRRC metastases. Patients with synchronous LRRC metastases had worse survival compared to patients without metastases (adjusted hazard ratio: 1.56 [1.15–2.12]), whilst survival of patients with synchronous primary metastases and metachronous metastases of the primary tumour was similar as those patients who had no metastases. In LRRC patients who had metastases in primary-recurrence interval, patients with early metachronous metastases had better disease-free survival as patients with late metachronous metastases (3-year disease-free survival: 48% vs 22%, p = 0.039). ConclusionLRRC patients with synchronous distant metastases undergoing curative surgery have relatively poor prognosis. However, LRRC patients with a history of distant metastases diagnosed nearby the primary tumour have comparable (oncological) survival as LRRC patients without distant metastases.

Short-term outcomes of health-related quality of life in patients with locally recurrent rectal cancer: multicentre, international, cross-sectional cohort study.

Overall survival rates for locally recurrent rectal cancer (LRRC) continue to improve but the evidence concerning health-related quality of life (HrQoL) remains limited. The aim of this study was to describe the short-term HrQoL differences between patients undergoing surgical and palliative treatments for LRRC. An international, cross-sectional, observational study was undertaken at five centres across the UK and Australia. HrQoL in LRRC patients was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CR29 and functional assessment of cancer therapy - colorectal (FACT-C) questionnaires and subgroups (curative versus palliative) were compared. Secondary analyses included the comparison of HrQoL according to the margin status, location of disease and type of treatment. Scores were interpreted using minimal clinically important differences (MCID) and Cohen effect size (ES). Out of 350 eligible patients, a total of 95 patients participated, 74.0 (78.0 per cent) treated with curative intent and 21.0 (22.0 per cent) with palliative intent. Median time between LRRC diagnosis and HrQoL assessments was 4 months. Higher overall FACT-C scores denoting better HrQoL were observed in patients undergoing curative treatment, demonstrating a MCID with a mean difference of 18.5 (P < 0.001) and an ES of 0.6. Patients undergoing surgery had higher scores denoting a higher burden of symptoms for the EORTC CR29 domains of urinary frequency (P < 0.001, ES 0.3) and frequency of defaecation (P < 0.001, ES 0.4). Higher overall FACT-C scores were observed in patients who underwent an R0 resection versus an R1 resection (P = 0.051, ES 0.6). EORTC CR29 scores identified worse body image in patients with posterior/central disease (P = 0.021). Patients undergoing palliative chemoradiation reported worse HrQoL scores with a higher symptom burden on the frequency of defaecation scale compared with palliative chemotherapy (P = 0.041). Several differences in short-term HrQoL outcomes between patients undergoing curative and palliative treatment for LRRC were documented. Patients undergoing curative surgery reported better overall HrQoL and a higher burden of pelvic symptoms.

Pathologic complete response after neoadjuvant chemotherapy/(re)chemoradiation for pelvic relapse of rectal cancer undergoing complex pelvic surgery: more frequent than expected?

To estimate the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy/(re)chemoradiation and its impact on survival in locally recurrent rectal cancer (LRRC) and to identify predictors of pCR or differences between neoadjuvant treatments. Among 394 LRRC patients treated at the National Cancer Institute of Milan (Italy), 74 (27.8%) were treated with neoadjuvant chemotherapy with or without (re)chemoradiation before surgery. The pCR rate was estimated, and its impact on 5-year survival was evaluated with the Kaplan-Meier survival method. Univariate analysis was performed to find pre-treatment predictors of pCR. After surgery, in 12 (16.2%) patients, a pCR was observed. All patients who reached pCR had R0 margins after surgery; among the 62 non-pCR patients, R0 margins were obtained in 29 (46.8%) cases only (p = 0.0004). pCR patients showed a significantly higher 5-year overall survival compared to non-pCR cases (33.3% vs. 21.0%, p = 0.045) and a trend toward better 5-year re-local recurrence-free survival. On univariate analysis, no predictor of pCR was found in the present study based on pre-treatment features. Since pCR is significantly associated to R0 resection and 5-year overall survival, pCR could be a target for LRRC cure. However, pCR is currently unpredictable based on pre-treatment features.

Low baseline neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict increased overall survival in locally recurrent rectal cancer despite R1 margins.

Prognostic features in locally recurrent rectal cancer (LRRC), beyond R0 surgery, are unknown. Aim of the present study was to evaluate the prognostic role of peripheral immune estimators, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on survival outcomes in LRRC patients. 184 LRRC patients treated at the National Cancer Institute of Milan (Italy) were included. Optimal cut-off values for NLR and PLR were determined. Kaplan-Meier curves and multivariate Cox analyses were used to assess the 5-yr overall survival (OS) according to NLR and PLR, also considering margins status. NLR >3.9 (hazard ratio [HR] 3.96, P=0.049), PLR >275 (HR 5.39, P = 0.002) and size on imaging (HR 1.36, P = 0.044) were associated to worse OS. R+ patients with NLR >3.9 showed a significantly lower 5-yr OS compared to NLR ≤3.9 (13.5% vs. 36.7%, P<0.0001). Also PLR >275 was related with a lower 5-yr OS compared to PLR ≤275 in R+ patients (6.4% vs. 36.8%, P = 0.0003). Conversely, NLR and PLR were irrelevant in case of R0 surgery. NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases.

Metabolic positron emission tomography/CT response after induction chemotherapy and chemo(re)irradiation is associated with higher negative resection margin rate in patients with locally recurrent rectal cancer.

Positron emission tomography (PET)/CT can be used to monitor the metabolic changes that occur after intensified treatment with induction chemotherapy and chemo(re)irradiation for locally recurrent rectal cancer (LRRC). This study aimed to analyse the correlation between the PET/CT response and final histopathological outcomes. All LRRC patients who underwent induction chemotherapy prior to surgery between January 2010 and July 2020 and were monitored with pretreatment and post-treatment PET/CT were included. Visual qualitative analysis was performed, and patients were scored as having achieved a complete metabolic response (CMR), partial metabolic response (PMR) or no response (NR). The histopathological response was assessed according to the Mandard tumour regression (TRG) score and categorized as major (TRG 1-2), partial (TRG 3) or poor (TRG 4-5). The PET/CT and TRG categories were compared, and possible confounders were analysed. A total of 106 patients were eligible for analysis; 24 (23%) had a CMR, 54 (51%) had a PMR and 28 (26%) had NR. PET/CT response was a significant predictor of the negative resection margin rate, achieving 96% for CMR, 69% for PMR and 50% for NR. The overall accuracy between PET score and pathological TRG was 45%, and the positive predictive value for CMR was 63%. A longer interval between post-treatment PET/CT and surgery negatively influenced the predictive value. Metabolic PET/CT response evaluation after neoadjuvant treatment proves to be a complementary diagnostic tool to standard MRI in assessing tumour response, and may play a role for treatment planning in LRRC patients.

Surgical treatment of locally recurrent rectal cancer: a narrative review.

ObjectiveTo summarize the recent literature on surgical treatment of locally recurrent rectal cancer (LRRC).BackgroundLRRC is a heterogeneous disease that requires a multidisciplinary treatment approach. The treatment and prognosis depend on the site and type of recurrence. Radical resection remains the primary method for achieving long-term survival and improving symptom control. Preoperative chemoradiotherapy can reduce tumor volume and improve the R0 resection rate. Surgeons must clearly understand pelvic anatomy, develop a detailed preoperative plan, adopt a multidisciplinary approach for the surgical resection of the tumor as well as any invaded soft tissues, vessels, and bones, and ensure proper reconstruction. However, extended radical surgery often leads to a higher risk of postoperative complications and a low quality of life.MethodsWe searched English-language articles with keywords “locally recurrent rectal cancer”, “surgery” and “multidisciplinary team” in PubMed published between January 2000 to October 2020.ConclusionsLRRC is a complex problem. Long-term survival is not impossible following multidisciplinary treatment in appropriately selected LRRC patients. The management of LRRC relies on a specialist team that determines the biological behavior of the tumor and evaluates treatment options through multidisciplinary discussions, thereby balancing the surgical costs and benefits, alleviating postoperative complications, and improving patients’ quality of life.

Impact of surgical treatment for locally recurrent rectal cancer on the quality of life of patients

Objective: To investigate the impact of surgical treatment on quality of life in patients with locally recurrent rectal cancer (LRRC). Methods: A descriptive case series study was performed. The complete clinical data of 62 patients who met the diagnostic criteria of LRRC and treated by surgical procedures in Huashan Hospital of Fudan University from January 2012 to November 2019 were analyzed retrospectively. All the patients were followed up at least 12 months. Assessments of urinary function, sexual function, mobility function of lower limb and quality of life were documented. Patients with distant metastasis and surgical history of the urinary system were excluded. According to the criteria of Memorial Sloan Kettering Cancer Center (MSKCC), recurrence were divided into central (n=27), anterior (n=20), posterior (n=7), and lateral (n=8) subtypes. Baseline characteristics, surgical procedures and short-term complications were analyzed. International prostate symptom score (IPSS) and grade of voiding dysfunction were used to evaluate the urinary function. Higher score of IPSS and higher grade of voiding dysfunction indicated worse voiding function. Sexual function for both genders was assessed preoperatively and postoperatively. International index of erectile function-5 (IIEF-5) was used for assessment of male patients and higher score indicated better function. Female sexual function index (FSFI) was used in females and higher score indicated better function. Short-form health survey with 36 items (SF-36), yielding an 8-scale profile of functional health (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, emotional health and mental health) was used to evaluate the quality of life. The higher score indicated the better quality of life. Results: All the operations of 62 patients completed successfully and R0 resection rate was 88.7% (55/62). Postoperative surgical complications occurred in 16 cases (25.8%), including 3 patients of Clavien-Dindo classification III. At postoperative 3-month, 42 patients without ileum cystectomy or ureterostomy suffered from different grade of voiding dysfunction. IPSS increased significantly after the surgery (before surgery: 12.36±4.75, after surgery: 18.40±4.77, t=-9.128, P<0.001). There was no significant difference among the subtypes (P>0.05). At postoperative 12-month, IIEF-5 decreased from 14 (0~25) to 9 (0~19) in males (Z=-5.174, P<0.001) and FSFI deceased from 8.4 (2.0-27.0) to 2.0 (2.0-18.4) in females (Z=-3.522, P<0.001). Scores of physical functioning and role-physical decreased significantly [physical functioning: before surgery 70 (35-85), after surgery 65 (30-80), Z=-3.685, P<0.001; role-physical: before surgery 50 (0-50), after surgery 25(0-75), Z=-4.065, P<0.001], while those of social functioning role-emotional and mental health increased significantly after the surgery [social functioning: before surgery 44 (22-78), after surgery 56 (0-89), Z=-3.509, P<0.001; role-emotional: before surgery 17 (0-100), after surgery 33 (0-100), Z=-2.439, P=0.015; mental health: before surgery 40 (36-76), after surgery 52 (24-80), Z=-3.395, P<0.001]. All surgical procedures decreased the voiding function of LRRC patients and the sexual function of male patients (all P<0.01). However, only total pelvic exenteration and posterior pelvic exenteration decreased FSFI in female patients [before surgery: 8.4 (2.0-27.0) after surgery: 2.0 (2.0-18.4), Z=-2.810, P=0.005]. Conclusions: Multi-visceral resection in LRRC patients may damage voiding and sexual function. However, successful and effective surgical treatment can improve the psychosocial health of LRRC patients.

The dosimetry evaluation of 3D printing non-coplanar template-assisted CT-guided 125I seed stereotactic ablation brachytherapy for pelvic recurrent rectal cancer after external beam radiotherapy.

ABSTRACTThe aim of this study was to investigate the safety and accuracy of computed tomography (CT)-guided 125I seed implantation assisted by a three-dimensional printing non-coplanar template (3D-PNCT) for treating pelvic locally recurrent rectal cancer (LRRC) patients. A total of 13 patients with 18 masses received 125I seed implantation. The dosimetric parameters of pre-implantation and post-implantation were calculated to evaluate the quality of 125I seed implantation. Doses delivered to the organs at risk (OAR) were also calculated. Differences between pre-implantation and post-implantation were compared by the paired t-test. The mean number of 125I seeds pre-implantation and post-implantation was 67.1 and 68.8, respectively. The mean values of D90 (dose that was delivered to 90% of the target volume), D100 (dose that was delivered to 100% of the target volume), V100 (the target volume receiving 100% of the prescription dose) and V150 (the target volume receiving 150% of the prescription dose) pre-implantation and post-implantation were 136.6 and 135.2 Gy, 63.5 and 71.0 Gy, 90.3% and 90.3% and 62.1% and 62.2%, respectively. Dosimetric outcomes were evaluated quantitatively using the dose volume indices, i.e. coverage index (CI), external volume index (EI) and relative dose homogeneity index (HI). The mean values of those indices pre-implantation and post-implantation were 0.62 and 0.61, 0.31 and 0.33, and 0.31 and 0.31, respectively. The mean doses delivered to OAR pre-implantation and post-implantation for the bladder (D2cc) and bowel (D2cc) were 33.4 and 34.4 Gy, and 58.6 and 61.8 Gy, respectively. The parameters mentioned above fitted well, and no significant difference was found among them. It is concluded that CT-guided 125I seed implantation assisted by 3D-PNCT could be a safe and accurate salvage modality for treating LRRC patients; the ideal pre-prescription dose could be achieved. Also, addition of 3D-PNCT could minimize radiation damage to the surrounding normal tissues.

Impact of a history of metastases or synchronous metastases on survival in patients with locally recurrent rectal cancer.

Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases. All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis. Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3-year metastasis-free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P<0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98-2.11). LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis-free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.

Age-related differences in morbidity and mortality after surgery for primary clinical T4 and locally recurrent rectal cancer.

Outcomes in elderly patients (≥75years) with non-advanced colorectal cancer have improved. It is unclear whether this is also true for elderly patients with clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). We aimed to compare age-related differences in morbidity and mortality after curative treatment for cT4RC and LRRC. All cT4RC and LRRC patients without distant metastasis who underwent curative surgery between 2005 and 2017 in the Catharina Hospital (Eindhoven, The Netherlands) were included. Morbidity and mortality were evaluated based on age (<75 and ≥75years) and date of surgery (2005-2011 and 2012-2017). Overall, 72 of 474 (15.2%) cT4RC and 53 of 293 (18.1%) LRRC patients were ≥75years. Nosignificantdifferences in the incidence of Clavien-Dindo I-IV complications were observed between age groups. However, in elderly cT4RC patients, cerebrovascular accidents occurred more frequently (4.2% vs. 0.5%, P=0.03). Between 2005-2011 and 2012-2017, 30-day mortality improved from 7.5% to 3.1% and from 10.0% to 0.0% in elderly cT4RC and LRRC patients, respectively. The 1-year mortality during 2012-2017 was worse in elderly than in younger patients (28.1% vs. 6.2%, P=0.001 for cT4RC and 27.3% vs. 13.8%, P=0.06 for LRRC). In elderly cT4RC and LRRC patients, 44.4% and 46.2% died due to non-cancer-related causes, while only 27.8% and 23.1% died due to disease recurrence, respectively. Although the 30-day mortality in elderly cT4RC and LRRC patients improved after curative treatment, the 1-year mortality in elderly patients continued to be high, which requires more awareness for the elderly after hospitalization.

Prediction of R0/R+ surgery by different classifications for locally recurrent rectal cancer.

A widely adopted classification system for locally recurrent rectal cancer (LRRC) is currently missing, and the indication for surgery is not standardized. To evaluate all the published classification systems in a large monocentric cohort of LRRC patients, assessing their capability to predict a radical (R0) resection. A total of 152 consecutive LRRC patients treated at the National Cancer Institute of Milan (NCIM) from 2009 to 2017 were classified according to Pilipshen, Mayo Clinic, Memorial Sloan-Kettering Cancer Center (MSKCC), Wanebo, Yamada, Boyle, Dutch TME Trial, Royal Marsden and National Cancer Institute of Milan (NCIM) classification systems. Central location of LRRC was significantly predictive of R0 resection across all classification systems. R + resection was predicted by the "anterior" category of MSKCC (OR 2.66, p = 0.007), the "S2b" (OR 3.50, p = 0.04) and the "S3" (OR 2.70, p = 0.01) categories of NCIM, "pelvic disease through anastomosis" of Pilipshen (OR 2.89, p = 0.002), "fixed at 2 sites" of Mayo Clinic (OR 2.68, p = 0.019), and "TR4" of Wanebo (OR 3.39, p = 0.002). The NCIM was the most predictive classification for R0 surgery. The NCIM classification seems to be superior among the others in predicting R0 surgery. Generally, lateral invasive and high sacral invasive relapses are associated with reduced probability of R0 surgery and unfavorable outcomes.

Treatment and subsequent prognosis in locally recurrent rectal cancer: a multicenter retrospective study of 498 patients.

Locally recurrent rectal cancer (LRRC) has a tremendous impact on prognosis as well as the quality of life. Because of the low incidence and various recurrence patterns, the treatment outcome of LRRC is not fully elucidated. The current study aimed to evaluate the prognosis and identify the prognosticators in patients with LRRC. We conducted a multicenter study at 24 hospitals in Japan. Patients with primary rectal cancer who underwent curative resection between 1997 and 2012 and developed local recurrence only as a first recurrent event were recruited. The primary outcome of our study was overall survival (OS) after a diagnosis of LRRC. Four hundred and ninety-eight patients were included in the study. Of these, 213 (42.8%) underwent surgical resection; this was associated with the best 5-year OS rate of 52%, followed by carbon ion/proton therapy (44%). Among LRRC patients, undifferentiated type, T4, high CEA level, and high CA19-9 level were independent prognosticators of OS (hazard ratio (HR) = 1.83, P = 0.008, HR = 1.54, P = 0.004, HR = 1.35, P = 0.03, and HR = 1.58, P = 0.003, respectively). This large-scale cohort study showed that surgical resection led to a favorable prognosis compared to other treatments for LRRC. Therefore, surgical resection should be considered whenever feasible for LRRC patients. In addition, undifferentiated type, T4, and tumor marker (CEA and CA19-9) elevation were identified as independent prognostic factors for OS among patients with LRRC.

Long-Term Outcomes and Prognostic Analysis of Computed Tomography-Guided Radioactive 125I Seed Implantation for Locally Recurrent Rectal Cancer After External Beam Radiotherapy or Surgery

BackgroundManagement of locally recurrent rectal cancer (LRRC) after surgery or external beam radiotherapy (EBRT) remains a clinical challenge, given the limited treatment options and unsatisfactory outcomes. This study aimed to assess long-term outcomes of computed tomography (CT)-guided radioactive 125I seed implantation in patients with LRRC and associated prognostic factors.MethodsA total of 101 patients with LRRC treated with CT-guided 125I seed implantation from October 2003 to April 2019 were retrospectively studied. Treatment procedures involved preoperative planning design, 125I seed implantation, and postoperative dose evaluation. We evaluated the therapeutic efficacy, adverse effects, local control (LC) time, and overall survival (OS) time.ResultsAll the patients had previously undergone surgery or EBRT. The median age of patients was 59 (range, 31–81) years old. The median follow-up time was 20.5 (range, 0.89–125.8) months. The median LC and OS time were 10 (95% confidence interval (CI): 8.5–11.5) and 20.8 (95% CI: 18.7–22.9) months, respectively. The 1-, 2-, and 5-year LC rates were 44.2%, 20.7%, and 18.4%, respectively. The 1-, 2-, and 5-year OS rates were 73%, 31.4%, and 5%, respectively. Univariate analysis of LC suggested that when short-time tumor response achieved partial response (PR) or complete response (CR), or D90>129 Gy, or GTV ≤ 50 cm3, the LC significantly prolonged (P=0.044, 0.041, and <0.001, respectively). The multivariate analysis of LC indicated that the short-time tumor response was an independent factor influencing LC time (P<0.001). Besides, 8.9% (9/101) of the patients had adverse effects (≥grade 3): radiation-induced skin reaction (4/101), radiation-induced urinary reaction (1/101), fistula (2/101), and intestinal obstruction (2/101). The cumulative irradiation dose and the activity of a single seed were significantly correlated with adverse effects ≥grade 3 (P=0.047 and 0.035, respectively).ConclusionCT-guided 125I seed implantation is a safe and effective salvage treatment for LRRC patients who previously underwent EBRT or surgery. D90 and GTV significantly influenced prognosis of such patients.

Dosimetric comparison of computed tomography-guided iodine-125 seed implantation assisted with and without three-dimensional printing non-coplanar template in locally recurrent rectal cancer: a propensity score matching study.

PurposeTo compare post-implant dosimetric parameters of computed tomography (CT)-guided radioactive iodine-125 (125I) seed (RIS) implantation assisted with and without three-dimensional printing non-coplanar template (3D-PNCT) in locally recurrent rectal cancer (LRRC).Material and methodsOne hundred and fifty-five LRRC patients treated by CT-guided RIS implantation assisted with or without 3D-PNCT from October 2003 to May 2019 were included in this study. Propensity score matching (PSM) method (1 : 1) was used to adjust for differences between the 3D-group (with 3D-PNCT) and the CT-group (without 3D-PNCT). After PSM, dosimetric parameters [D90 (dose that covered 90% of target volume), D100 (dose that covered 100% of target volume), V100 (percentage of gross tumor volume (GTV) receiving 100% of prescription dose), V150 (percentage of GTV receiving 150% of prescription dose), HI (homogeneity index), CI (conformity index), and EI (external index)] of the two groups were compared.ResultsAfter PSM, 45 pairs of matched cases were selected for analysis and differences in variables between the two groups were balanced. For the 3D-group, median values of D90, D100, V100, V150, EI, and HI were 142.6 Gy (73.7-218.2 Gy), 73.7 Gy (26.2-169.3 Gy), 94.1% (74.3-100%), 71.8% (35.4-98.3%), 0.7 (0.1-30.7), and 0.20 (0-0.60), respectively, and corresponding values were 119.9 Gy (39.8-159.3 Gy), 47.0 Gy (13.0-200.9 Gy), 89.9% (38.6-100%), 62.8% (14.8-100%), 0.39 (0-11.01), and 0.30 (0-0.95), respectively, for the CT-group. Parameters including D90, D100, V100, V150, and EI in the 3D-group were significantly higher than those in the CT-group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p = 0.006, respectively).Conclusions3D-PNCT can improve the accuracy of radioactive seed implantation by increasing the dose delivered to the tumor and reducing the number of “cold” spots of dose.