Advanced Rectal Cancer Patients Research Articles

The efficacy and safety of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer patients: a systematic review

BackgroundSeveral studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer.MethodsThe PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs).ResultsFourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively.ConclusionIn cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023465380.

PTEN and P-4E-BP1 might be associated with postoperative recurrence of rectal cancer patients undergoing concurrent radiochemotherapy

BackgroundLocal recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment.AimTo find potential biomarkers of tumors for predicting postoperative recurrence.MethodsIn this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence.ResultsThe expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy.ConclusionsThis study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.

Analysis of risk characteristics for early progression and late progression in locally advanced rectal cancer patients: a large population-based and validated study.

The current study aimed to explore the factors influencing early progression (EP) and late progression (LP) in locally advanced rectal cancer (LARC) patients. The patients were classified into EP and LP groups using one year as a cutoff. The random survival forest model was utilized to calculate the probability of time-to-progression. Besides, inverse probability of treatment weighting (IPTW) analysis and the Surveillance, Epidemiology, and End Results (SEER) were conducted to validate our results. Our study revealed that PNI, CEA level, and pathological stage were independent prognostic factors for PFS both in EP group and LP group. For EP group patients, Group 1 had the highest probability of progression at the 9th month of follow-up, while Group 2 exhibited the highest probability at the 6th month. Group 3, on the other hand, showed two peaks of progression at the 4th and 8th months of follow-up. As for LP group patients, Groups 4, 5, and 6 all exhibited peaks of progression between the 18th and 24th months of follow-up. Furthermore, our results suggested that PNI was also an independent prognostic factor affecting OS in both EP group and LP group. Finally, the analysis of IPTW and SEER database further confirmed our findings. Our results indicated a significant correlation between immune and nutritional status with PFS and OS in both EP and LP groups. These insights can aid healthcare professionals in effectively identifying and evaluating patients' nutritional status, enabling them to develop tailored nutrition plans and interventions.

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-neutrophil (PN) index in locally advanced rectal cancer patients: a retrospective cohort study.

In locally advanced rectal cancers (LARC), tumour node metastasis (TNM) staging is far from optimal. The authors aimed to investigate the value of previously described circulating biomarkers as predictors of prognosis. Retrospective analysis of 245 LARC patients diagnosed between January 2010 and December 2022, who underwent neoadjuvant chemoradiotherapy and surgery at two centres. A Cox regression and Kaplan-Meier analysis were performed. Post-treatment platelet-to-lymphocyte ratio (PLR) predicted pathological complete response. The neutrophil-to-lymphocyte ratio (NLR) in two timepoints of the treatment significantly predicted overall survival, whereas the platelet-neutrophil (PN) index significantly predicted disease-free survival. In pathological stage II, the PN index predicted patients with a higher risk of disease-free survival. Blood parameters might allow the definition of subgroups of risk beyond TNM for the application of different therapeutic strategies.

Predicting survival in locally advanced rectal cancer with effective chemoradiotherapy response

BackgroundLocally advanced rectal cancer patients often display favorable responses and favorable oncologic outcomes. Due to the low recurrence rate, there is scarcity of studies investigating the prognostic factors influencing their survival. Therefore, our study sought to assess the prognostic factors associated with survival in rectal cancer patients who achieved either a pathologic complete response or a pathologic stage I after neoadjuvant chemoradiotherapy combined with radical resection. MethodsIn this retrospective study, we analyzed data from cohort of 1394 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy combined with total mesorectal excision from January 2008 to April 2017. Finally, we selected 474 (34.2 %) who exhibited either a pathologic complete response or attained pathologic stage I following the treatment. Subsequently, we analyzed the prognostic factors influencing disease-free and overall survival. ResultsA total of 161 (34 %) achieved a pathologic complete response. Our analysis revealed that circumferential resection margin and the administration of adjuvant chemotherapy were prognostic factors for disease-free survival (p = 0.011, p = 0.022). Furthermore, factors influencing overall survival included the clinical N stage and administration of adjuvant chemotherapy (p = 0.035, p = 0.015). ConclusionIn conclusion, the circumferential resection margin, clinical N stage, and administration of adjuvant chemotherapy were prognostic factors for survival in patients showing good response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. For patients with a positive circumferential resection margin and clinical N (+) stage, intensive follow-up might be needed to achieve favorable oncologic outcomes. Also, we recommend considering adjuvant chemotherapy as a beneficial treatment approach for these patients.

The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer

BackgroundThis study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. MethodsThe EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. ResultsA higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. ConclusionHerein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35T MRI-guided radiotherapy study.

The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. Patients from three international sites were included and divided into training and validation sets. 0.35T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35T MRIgRT treatments of LARC patients.

Rectal Cancer Survival for Residual Carcinoma In Situ Vs. Pathologic Complete Response After Neoadjuvant Therapy.

Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. To compare survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. Retrospective cohort study. National public database. A total of 4,594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative, ypTis or ypT0 on final pathology were included. 4,321 (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. Overall survival. Median age was 60 years. 1,822 patients (39.7%) were female. 54.5% (n = 2,503) had stage II disease and 45.5% (n = 2,091) had stage III disease on initial staging. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42, 95% CI 1.04-1.95, p = 0.028). Other factors associated with decreased overall survival were an older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage 2 versus stage 3. Standard therapy versus total neoadjuvant therapy were unable to be abstracted. Overall survival was defined as time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. ypTis is associated with worse overall survival than ypT0 for locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract.

Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT3-4aN0M0 and cT1-4aN1-2M0) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850–1000 mg/m2, bid, po, day1–14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6–12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61–53.82%], while 15 (30.0%, 95% CI: 19.1–43.75%), 9 (18.0%, 95% CI: 9.77–30.8%), 2 (4.0%, 95% CI: 1.10–13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

Prediction of pathologic complete response to neoadjuvant chemoradiation in locally advanced rectal cancer.

To investigate the predictive factors of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) patients who had been treated with neoadjuvant chemoradiation (nCRT). For this retrospective study, 53 LARC patients (37 males and 16 females; age range 25 to 79 years) were selected. Clinical characteristics, baseline mrTNM staging, MR gross tumor volumes (GTV), and pCR were evaluated. The diagnostic accuracy of GTV for predicting pCR was calculated. Among 53 LARC patients, 15 patients achieved pCR (28.3%), while 38 patients achieved non-pCR. Only three (5.7%) out of 53 patients did not downstage after nCRT. GTV and tumor differentiation were the significant prognostic parameters for predicting pCR. A tumor volume threshold of 21.1 cm3 was determined as a predictor for pCR, with a sensitivity of 84% and specificity of 47%. In addition, GTV was associated with mrN stage, circumferential resection margin (CRM) status, extramural vascular invasion (EMVI) status, and pretreatment serum CEA level. Tumor volume and tumor differentiation have significant predictive values in preoperative assessment of pCR among LARC patients. These findings aid clinicians to discriminate those patients who may likely benefit from preoperative regimens and to make optimal treatment plans.

Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer

Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894–0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489–0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.

The Impact on Survival of Neoadjuvant Treatment Interruptions in Locally Advanced Rectal Cancer Patients.

The standard oncologic treatment of locally advanced rectal cancer is long-course radio-chemotherapy followed by surgery and adjuvant chemotherapy. This can result in a lengthy total treatment duration, sometimes up to one year from the diagnosis. Interruptions to neoadjuvant treatment can occur for a variety of reasons, forced or unforced. The main purpose of this study is to analyze the survival data of locally advanced rectal cancer patients who received neoadjuvant treatment and to find a cut-off point showing exactly how many days of interruption of neoadjuvant treatment the risk of death or disease relapse increases. We conducted a retrospective study on 299 patients with locally advanced rectal cancer using survival analysis (Kaplan-Meier curve and Cox regression) to determine survival probabilities for overall survival, local control, and disease-free survival. Patients with 0 to 3 days of neoadjuvant therapy interruption had a higher overall survival probability compared to patients with 4 or more days (90.2% compared to 57.9%, p-value < 0.001), hazard ratio 5.89 (p < 0.001). Local control and disease-free survival had a higher probability in patients with 0-2 days of interruption compared to people with 3 or more days (94% vs. 75.4%, and 82.2% vs. 50.5%, respectively, both p-values < 0.001). Patients with tumoral or nodal downstaging experienced fewer days of interruption than patients with no downstage. These findings reinforce the need for radiation oncologists to be well-organized when starting neoadjuvant treatment for rectal cancer, in order to anticipate and prevent potential treatment interruptions and achieve the best therapeutic results.

Expression of Mitochondrial Long Non-Coding RNAs, MDL1 and MDL1AS, Are Good Prognostic and/or Diagnostic Biomarkers for Several Cancers, Including Colorectal Cancer.

Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases. In addition, a cohort of 69 locally advanced rectal cancer (LARC) patients with a follow-up of more than 5 years was used to determine the prognostic value of these markers. Furthermore, cell lines of colorectal (HCT116) and breast (MDA-MB-231) carcinoma were employed to study the effects of downregulating MDL1AS in vitro. Expression of MDL1AS (but not MDL1) was significantly different in tumor cells than in the surrounding tissue in a tumor-type-specific context. Both MDL1 and MDL1AS were accurate biomarkers for the 5-year survival of LARC patients (p = 0.040 and p = 0.007, respectively) with promising areas under the curve in the ROC analyses (0.820 and 0.930, respectively). MDL1AS downregulation reduced mitochondrial respiration in both cell lines. Furthermore, this downregulation produced a decrease in growth and migration on colorectal cells, but the reverse effects on breast cancer cells. In summary, MDL1 and MDL1AS can be used as reliable prognostic biomarkers of LARC, and MDL1AS expression provides relevant information on the diagnosis of different cancers.

Prediction of liver metastasis and recommended optimal follow-up nursing in rectal cancer.

We aimed to analyze and investigate the clinical factors that influence the occurrence of liver metastasis in locally advanced rectal cancer patients, with an attempt to assist patients in devising the optimal imaging-based follow-up nursing. Between June 2011 and May 2021, patients with rectal cancer at our hospital were retrospectively analyzed. A random survival forest model was developed to predict the probability of liver metastasis and provide a practical risk-based approach to surveillance. The results indicated that age, perineural invasion, and tumor deposit were significant factors associated with the liver metastasis and survival. The liver metastasis risk of the low-risk group was higher at 6-21 months, with a peak occurrence time in the 15th month. The liver metastasis risk of the high-risk group was higher at 0-24 months, with a peak occurrence time in the 8th month. In general, our clinical model could predict liver metastasis in rectal cancer patients. It provides a visualization tool that can aid physicians and nurses in making clinical decisions, by detecting the probability of liver metastasis.

The clinical relevance of adjuvant chemotherapy in locally advanced rectal cancer patients achieving near pathological complete response following neoadjuvant chemoradiotherapy: Insights from ypT stage

BackgroundNear-pathological complete response (Near-pCR) patients constitute a distinct subgroup with limited research attention. The clinical relevance of adjuvant chemotherapy (ACT) in this patient cohort remains uncertain. MethodsWe conducted a retrospective analysis of 245 patients with locally advanced rectal cancer (LARC) who achieved near-pCR following neoadjuvant chemoradiotherapy (NCRT) between 2011 and 2018. Based on their receipt of ACT or not (non-ACT), patients were divided into two groups. We examined their characteristics, treatment modalities, and survival outcomes, particularly focusing on 5-year disease-free survival (DFS) and 5-year overall survival (OS). ResultsAmong the 245 near-pCR patients, 191 (77.96%) received ACT, and 42 (17.14%) experienced disease recurrence. All 54 (22.04%) Patients in the non-ACT group exhibited a lower 5-year DFS rate (72.2% vs. 85.9%, P = 0.014) and a similar 5-year OS rate (87.0% vs. 91.1%, P = 0.351). Interestingly, those with ypT3-T4 stage tumors demonstrated a worse DFS (76.8% vs. 89.9%, P = 0.010) and OS (87.5% vs. 97.0%, P = 0.004) compared to their counterparts with ypT1-T2 stage tumors. Patients with Non-Downstage tumors showed inferior DFS (76.9% vs. 88.3%, P = 0.025) and OS (87.2% vs. 93.0%, P = 0.166) in comparison to patients with Downstage tumors. The ACT subgroup in patients with Downstage demonstrated statistically better 5-year DFS (93.0% vs. 71.4%, P = 0.001) but analogous survival rates for 5-year OS (OS: 94.0% vs. 89.3%, P = 0.402). Pathological T stage 3–4, perineural invasion (PNI) (positive) and ACT were independent factors influencing 5-year DFS in multivariate analysis. Both univariate and multivariate analysis demonstrated a link between serum carcinoembryonic antigen (CEA) before treatment ≥5 ng/ml and shorter 5-year OS. Notably, near-pCR patients with positive lymph nodes experienced notably diminished 5-year DFS in the absence of ACT post-surgery (61.1% vs. 93.2%, P < 0.001). ConclusionsACT demonstrated a significant positive impact on the prognosis of select near-pCR patients, particularly those with ypT1-T2 stage tumors and positive lymph nodes. ypT staging may emerge as a valuable criterion for precise post-surgical ACT guidance in near-pCR patients.

Effect of adjuvant chemotherapy on the oncological outcome of rectal cancer patients with pathological complete response

BackgroundLocally advanced rectal cancer is typically treated using a combination of neoadjuvant chemoradiotherapy and total mesorectal resection. While achieving pathological complete response following neoadjuvant chemoradiotherapy has been recognized as a positive prognostic factor in oncology, the necessity of adjuvant chemotherapy for locally advanced rectal cancer patients with pathological complete response after surgery remains uncertain. The objective of this meta-analysis was to examine the impact of adjuvant chemotherapy on the oncological outcomes of rectal cancer patients who attain pathological complete response after neoadjuvant chemoradiotherapy.MethodsThis meta-analysis followed the guidelines outlined in the preferred reporting items for systematic review and meta-analysis (PRISMA). The Web of Science, PubMed, and Cochrane Library databases were systematically searched to identify relevant literature.ResultsA total of 34 retrospective studies, including 9 studies from the NCBD database, involving 31,558 patients with pathological complete response rectal cancer, were included in the meta-analysis. The included studies were published between 2008 and 2023. The pooled analysis demonstrated that adjuvant chemotherapy significantly improved overall survival (HR = 0.803, 95% CI 0.678–0.952, P = 0.011), and no heterogeneity was observed (I2 = 0%). Locally advanced rectal cancer patients with pathological complete response who underwent adjuvant chemotherapy exhibited a higher 5-year overall survival rate compared to those who did not receive adjuvant chemotherapy (OR = 1.605, 95% CI 1.183–2.177, P = 0.002). However, the analysis also revealed that postoperative ACT did not lead to improvements in disease-free survival and recurrence-free survival within the same patient population. Subgroup analysis indicated that pathological complete response patients with clinical stage T3/T4, lymph node positivity, and younger than 70 years of age may benefit from adjuvant chemotherapy in terms of overall survival.ConclusionsThe findings of this meta-analysis suggest that adjuvant chemotherapy has a beneficial effect on improving overall survival among rectal cancer patients with pathological complete response. However, no such association was observed in terms of disease-free survival and recurrence-free survival.

The impact of multidisciplinary care for locally advanced rectal cancer referrals: A systems perspective.

85 Background: Locally advanced rectal cancer patients require multidisciplinary care for treatment planning. We sought to determine whether the order of surgical and radiation oncology consultation in relation to medical oncology consultation affects the time from cancer diagnosis to treatment initiation and the requirement for additional pre-treatment visits with medical oncology. Methods: We conducted a retrospective chart review of adult patients referred to The Ottawa Hospital with locally advanced rectal adenocarcinoma, seen in consultation by a surgical, radiation, and medical oncologist between January 2018 and December 2022. Results: Of 195 patients, the median time from diagnosis to treatment was 55 days (IQR: 45-68). Both surgical and radiation oncology consultation preceded medical oncology consultation in a minority of patients (72; 37%), and 48 (25%) patients required multidisciplinary cancer conference (MCC) discussion. However, the time from cancer diagnosis to treatment initiation was not significantly different between patients who were and were not seen by the surgeon and radiation oncologist prior to the medical oncologist (56 vs. 55 days respectively), nor if MCC discussions were or were not required (55 vs. 55 days). However, almost half of all patients (93; 48%) required an additional pre-treatment visit with their medical oncologist, and patients who saw both surgical and radiation oncology prior were significantly less likely to require additional pre-treatment visits with medical oncology (25% vs. 61%; p&lt;0.0001). Conclusions: The time from cancer diagnosis to treatment initiation was not significantly impacted by the order of specialist consultations with the multidisciplinary team, nor if patients required MCC discussion or additional pre-treatment visits with medical oncology. However additional pre-treatment visits with medical oncology were significantly more likely to occur when patients were seen by medical oncology prior to surgical and/or radiation oncology, representing a logistical and financial inefficiency in the system, and a potential area for process improvement. [Table: see text]

Is radiotherapy necessary for upper rectal cancer underwent curative resection? A retrospective study of 363 patients

BackgroundTo investigate the impact of radiotherapy (RT) on recurrence and survival in patients with locally advanced upper rectal cancer underwent curative resection.Methods363 locally advanced upper rectal cancer cases were identified from the database of our hospital from 2010 to 2018. All patients underwent curative resection and had the lower margin of the tumor located 10–15 cm from the anal verge, among them, 69 patients received pre- or post-operative radiotherapy and 294 patients without. Local control and survivals were compared, and stratification grouping based on European Society for Medical Oncology risk factors were further compared. 1:2 propensity score matching analysis was used to reduce the impact of confounding factors.ResultsThere were 207 patients after 1:2 matching (RT group:non-RT group = 69:138). The 5-year overall survival (OS) of the RT group and non-RT group after matching was 84.1% and 80.9%, respectively(P = 0.440); the 5-year local recurrence-free survival (LRFS) was 96.5% and 94.7%, respectively(P = 0.364); the 5-year distant metastasis-free survival (DMFS) was 76.8% and 76.9%, respectively(P = 0.531). Subgroup analysis showed that radiotherapy could not significantly improve the overall survival, local recurrence, and distant metastasis with or without poor prognostic features. In the high-risk subgroup, the 5-year OS was 76.9% and 79.6% for patients treated with radiotherapy and without (P = 0.798), LRFS was 94.8% and 94.2%, respectively (P = 0.605), DMFS 68.7% and 74.7%, respectively (P = 0.233).ConclusionsOur results suggest that radiotherapy could not improve local control and survival for locally advanced upper rectal cancer patients underwent curative resection, even in the cases with poor prognostic features.

Clinical and pathological parameters predicting pathologic complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective The aim of this study is to identify possible clinical predictors of complete response after neoadjuvant treatment in locally advanced rectal cancer (LARC) patients. Background Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision and postoperative adjuvant chemotherapy for LARC is the standard of care with a local recurrence rate of only 5–10%. On the other hand, various people react differently to neoadjuvant CRT. Neoadjuvant CRT is well received by the majority of patients, with a pathologic complete response (pCR) occurring in 10–30% of cases. Predicting the response to neoadjuvant CRT is crucial from a clinical standpoint, since patients with pCR have a better prognosis and may require a different treatment plan than patients without pCR. As a result, predicting pCR following neoadjuvant CRT for rectal cancer continues to be extremely useful for treating physicians. To identify the clinical and pathological variables linked to a full response to preoperative CRT for rectal cancer, we assessed a group of patients with pCR in this study. Patients and methods The study included 153 patients with LARC that were enrolled in the study based on specific inclusion and exclusion criteria. Patients were treated by standard neoadjuvant therapy. Surgical resection was planned for 6–8 weeks after the completion of neoadjuvant CRT, irrespective of the response to CRT. Pathological examination was performed to assess pathological response in the resected specimen. pCR was defined as the absence of viable tumor cells in the surgical specimen, including lymph nodes. Results After neoadjuvant chemoradiation, the pCR rate for rectal cancer patients was 20.8%; patients were split into pCR and non-pCR groups. Age, sex, BMI, performance score, tumor stage, tumor differentiation, tumor location, and surgical method were all evenly distributed across the two groups. The results of the multivariate analysis showed that pretreatment lymph node status, tumor size, and a carcinoembryonic antigen level of less than or equal to 5 ng/ml were independent risk factors of an elevated likelihood of pCR, as was an interval of more than or equal to 8 weeks between the completion of chemoradiation and treatment. Conclusion The pCR in rectal cancer following neoadjuvant chemoradiation is predicted by pretreatment carcinoembryonic antigen level of less than or equal to 5 ng/ml, an interval of more than or equal to 8 weeks between the end of chemoradiation and surgical resection, tumor size greater than 5 cm, and pretreatment lymph node status. By utilizing these predictive variables, we are able to forecast patients’ outcomes and create flexible treatment plans. In certain, very specific situations, a wait-and-see policy might be appropriate.

Machine Learning-Based Prediction of Responsiveness to Neoadjuvant Chemoradiotheapy in Locally Advanced Rectal Cancer Patients from Endomicroscopy.

The protocol for treating locally advanced rectal cancer consists of the application of chemoradiotherapy (neoCRT) followed by surgical intervention. One issue for clinical oncologists is predicting the efficacy of neoCRT in order to adjust the dosage and avoid treatment toxicity in cases when surgery should be conducted promptly. Biomarkers may be used for this purpose along with in vivo cell-level images of the colorectal mucosa obtained by probe-based confocal laser endomicroscopy (pCLE) during colonoscopy. The aim of this article is to report our experience with Motiro, a computational framework that we developed for machine learning (ML) based analysis of pCLE videos for predicting neoCRT response in locally advanced rectal cancer patients. pCLE videos were collected from 47 patients who were diagnosed with locally advanced rectal cancer (T3/T4, or N+). The patients received neoCRT. Response to treatment by all patients was assessed by endoscopy along with biopsy and magnetic resonance imaging (MRI). Thirty-seven patients were classified as non-responsive to neoCRT because they presented a visible macroscopic neoplastic lesion, as confirmed by pCLE examination. Ten remaining patients were considered responsive to neoCRT because they presented lesions as a scar or small ulcer with negative biopsy, at post-treatment follow-up. Motiro was used for batch mode analysis of pCLE videos. It automatically characterized the tumoral region and its surroundings. That enabled classifying a patient as responsive or non-responsive to neoCRT based on pre-neoCRT pCLE videos. Motiro classified patients as responsive or non-responsive to neoCRT with an accuracy of ~ 0.62 when using images of the tumor. When using images of regions surrounding the tumor, it reached an accuracy of ~ 0.70. Feature analysis showed that spatial heterogeneity in fluorescence distribution within regions surrounding the tumor was the main contributor to predicting response to neoCRT. We developed a computational framework to predict response to neoCRT by locally advanced rectal cancer patients based on pCLE images acquired pre-neoCRT. We demonstrate that the analysis of the mucosa of the region surrounding the tumor provides stronger predictive power.