High-risk Rectal Cancer Research Articles

Diagnostic Certainty in Characterizing Liver Lesions in Rectal Cancer: Abbreviated Liver MRI versus CT.

Early diagnosis of metastases is crucial but routine staging with contrast-enhanced multidetector computed tomography (ceMDCT) is suboptimal. A total of 20% will have indeterminate or too small to characterize (TSTC) liver lesions on CT, requiring formal characterization by magnetic resonance imaging (MRI). This UK cross-sectional study reports our experience undertaking routine abbreviated liver MRI (MRI). A total of 99 patients with rectal cancer had ceMDCT, abbreviated liver MRI, and rectal MRI at diagnosis. Liver imaging was scored for liver metastases, benign or indeterminate/TSTC lesions on a per patient basis. Primary rectal cancer was risk scored on MRI. A total of 42/99 (42%) had liver lesion(s) on ceMDCT versus 55/99 (56%) by MRI, and 46/99 (46%) had high-risk rectal cancer. ceMDCT showed 5 patients with liver metastases, 14 with benign lesions, and 23 with indeterminate/TSTC lesions. MRI showed 6 with liver metastases, 45 with benign lesions, and 4 with indeterminate/TSTC lesions. All liver metastases were in high-risk rectal cancer, OR 17.18 (p = 0.06), with 12.5% conversion rate of TSTC lesions to metastases in high-risk rectal cancer and 0% in low-risk rectal cancer. Diagnostic certainty of the liver findings was achieved in 93% of patients by MRI compared with 45% by ceMDCT (p < 0.0001). Abbreviated liver MRI diagnosed fewer indeterminate/TSTC lesions and provided greater diagnostic certainty than ceMDCT, p < 0.0001. High-risk rectal cancer is associated with a higher conversation rate of TSTC lesions to metastases than low-risk rectal cancers. Risk stratified; routine abbreviated liver MRI sequences should be investigated as part of the patient pathway for high-risk rectal cancer.

Simultaneous integrated boost to lateral pelvic lymph nodes during chemoradiotherapy in high-risk rectal cancer.

Preoperative chemoradiotherapy combined with total mesorectal excision (TME) is astandard treatment for locally advanced rectal cancer (LARC). However, lateral pelvic lymph nodes (LPLNs) are often inadequately treated with standard regimens. This study examines the treatment and postoperative outcomes in LARC patients receiving asimultaneous integrated boost (SIB) for LPLNs during long-course chemoradiotherapy. This retrospective study included high-risk LARC patients (UICC, "Union Internationale Contre le Cancer", stageIII) treated with preoperative chemoradiotherapy and SIB to LPLNs. Radiotherapy was delivered to the primary tumor and elective volumes with 50.4 Gy in 28fractions, and anSIB with amedian dose of 60.2 Gy was administered to clinically positive LPLNs. TME quality and postoperative complications were assessed using MERCURY and Clavien-Dindo, respectively. Time-to-event data were analyzed according to Kaplan-Meier. Between 2019 and 2023, 27patients with high-risk LARC and LPLN metastases were treated with chemoradiotherapy. After amedian follow-up of 19months, 2‑year overall survival was 80%, disease-free survival 80%, and local control of dose-escalated lymph nodes 100%. Three patients were managed nonoperatively after aclinical complete response on endoscopy and imaging. Of the 22patients who had surgery, only one had complications higher than Clavien-DindogradeI; TME was graded as MERCURYI in 73%. The SIB approach for LPLNs in LARC is feasible, does not increase postoperative morbidity, and achieves excellent local control. This study supports the consideration of dose-escalated radiotherapy for LPLNs to address high local recurrence risks.

Contact X-ray Brachytherapy (CXB) as a boost therapy after neoadjuvant (chemo)radiation in high-risk locally advanced rectal cancer.

Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A Contact X-ray Brachytherapy (CXB) boost can alternatively be used to treat residual disease post neoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low to intermediate-risk patients. We have now evaluated the utility of CXB-boost in high-risk rectal cancers after their tumours have been significantly downstaged by neoadjuvant (chemo)radiation. Oncological outcomes and treatment tolerability were evaluated in 328 patients based on rectal cancer treatment risk stratification: low/intermediate risk (cT1-3ab, N0-1, M0, no extramural invasion (EMVI), mesorectal fascia (MRF) involvement >1mm) and high-risk (cT3cd-4/N2, M0, MRF≤1mm and/or EMVI positive). With median follow-up of 33(IQR:15-54) months and median age of 73(IQR:62-80) years, no significant differences were found between low/intermediate and high-risk groups in clinical complete response (78% vs 73%, p=0.32), local regrowth (16.6% vs 22.4%, p=0.41), nodal (1.8% vs 5.8%, p=0.051) or regional (1.3% vs 2.9%, p=0.33) relapse, or post-radiation toxicities (p=0.16). However, the high-risk group had a higher distant relapse rate (21.2% vs 10.7%, p=0.01), with no significant differences in 3-year organ preservation (80% vs 87%, p=0.25), 5-year disease-free (DFS) (62% vs 64%, p=0.46), or overall (OS) survivals (67% vs 64%, p=0.88). Longer treatment time, treatment gap >24 weeks between therapies, and administration of a higher than standard CXB dose were newly identified factors that negatively impacted outcomes. High-risk rectal cancer patients treated with CXB-boost had more distant relapses, but comparable locoregional tumour control, organ preservation, DFS and OS to lower-risk patients, with acceptable toxicities. CXB-boost is therefore a viable option for selected high-risk rectal cancer patients. Timely reassessment, prompt referral, and CXB dose optimisation are crucial for improving outcomes.

Is an Electronic Nose Able to Predict Clinical Response following Neoadjuvant Treatment of Rectal Cancer? A Prospective Pilot Study.

Introduction: A watch-and-wait strategy for patients with rectal cancer who achieve a clinical complete response after neoadjuvant (chemo) radiotherapy is a valuable alternative to rectal resection. In this pilot study, we explored the use of an electronic nose to predict response to neoadjuvant therapy by analyzing breath-derived volatile organic compounds. Materials and Methods: A pilot study was performed between 2020 and 2022 on patients diagnosed with intermediate- or high-risk rectal cancer who were scheduled for neoadjuvant therapy. Breath samples were collected before and after (chemo) radiotherapy. A machine-learning model was developed to predict clinical response using curatively treated rectal cancer patients as controls. Results: For developing the machine-learning model, a total of 99 patients were included: 45 patients with rectal cancer and 54 controls. In the training set, the model successfully discriminated between patients with and without rectal cancer, with a sensitivity and specificity of 0.80 and 0.65, respectively, and an accuracy of 0.72. In the test set, the model predicted partial or (near) complete response with a sensitivity and specificity of 0.64 and 0.47, respectively, and an accuracy of 0.58. The AUC of the ROC curve was 0.63. Conclusions: The prediction model developed in this pilot study lacks the ability to accurately differentiate between partial and (near) complete responders with an electronic nose. Machine-learning studies demand a substantial number of patients and operate in a rapidly evolving field. Therefore, the prevalence of disease and duration of a study are crucial considerations for future research.

Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: How to Select the Most Suitable?

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6-7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.

Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer

Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. The primary end point was pathologic complete response rate. Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy. This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

Total neoadjuvant therapy: A new standard of care for locally advanced rectal cancer?

Delivering chemotherapy before surgery is a newer treatment approach called total neoadjuvant therapy (TNT), and the National Comprehensive Cancer Network guidelines recommend it for locally advanced rectal cancer (LARC) with cT3 / cN+ / cT4, in contrast with the European Society for Medical Oncology guidelines, in which most rectal cancers can be treated with surgery alone if good quality mesorectal resection is assured. Neoadjuvant or adjuvant treatments are reserved for patients with high-risk tumours, including cT3c/d or cT4, or that threaten the mesorectal fascia. The favourable outcomes in the RAPIDO trial for high-risk rectal cancers with a lower incidence of distant metastasis in the TNT group were observed but with an unexpected increase in the local recurrence with more extended follow-up. This suggests early surgery for nonresponding tumours. The TNT approach was also evaluated in the OPRA trial with long-course chemoradiotherapy and induction versus consolidation chemotherapy. Half the patients presented complete clinical responses and were enrolled in the watch-and-wait (WW) approach. Given the high number of trials and guidelines in this subject, the multidisciplinary team's decision-making process in rectal cancer management is complex. Looking at the actual data, it was concluded that TNT is not for all patients with LARC and is an option if organ preservation is a priority, although with a high regrowth rate in a WW strategy and increasing risk of distant metastasis, questioning the deleterious effect of deferral of surgery.

Real-world outcomes using total neoadjuvant therapy for high-risk rectal cancer

Real-world outcomes using total neoadjuvant therapy for high-risk rectal cancer

634P The ave-rec phase II trial of PD-L1/PD-1 blockade with avelumab plus chemoradiotherapy for resectable ESMO high risk rectal cancers

634P The ave-rec phase II trial of PD-L1/PD-1 blockade with avelumab plus chemoradiotherapy for resectable ESMO high risk rectal cancers

The RAPIDO trial-Reduction in disease-related treatment failure does not translate into improved overall survival: a mystery solved!

The initial publication of the RAPIDO trial resulted in widespread adoption of short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer. The impressive reduction in disease-related treatment failure did not, however, translate into any overall survival benefit. The recent update of the RAPIDO trial with its 5-year results provides much insight into the actual effect that this approach has on patient outcomes and the detriment in local control leads to the question as to whether this approach can still be considered as standard of care in high-risk rectal cancer.

Adjuvant chemotherapy for prevention of recurrence in patients with detectable ctDNA after surgery in high-risk rectal cancer

Adjuvant chemotherapy for prevention of recurrence in patients with detectable ctDNA after surgery in high-risk rectal cancer

Short-Term Outcomes and Cost-Effectiveness between Long-Course Chemoradiation and Short-Course Radiotherapy for Locally Advanced Rectal Cancer.

Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m² and oxaliplatin 130 mg/m² every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02).

Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

Preoperative short-course radiation therapy with PROtons compared to photons in high-risk RECTal cancer (PRORECT): Initial dosimetric experience

Background and purposeNeoadjuvant short-course radiotherapy(SCRT) followed by full-dose systemic chemotherapy is an established treatment modality in locally advanced rectal cancer (LARC). Until recently, SCRT has been exclusively delivered with photons. Proton beam therapy (PBT) may minimize acute toxicity, which in turn likely impacts favorably on the tolerability to subsequent chemotherapy. The aim of this study is a dosimetric comparison between SCRT with photons and protons in the randomized phase II trial PRORECT (NCT04525989). Materials and methodsFrom June 2021 to June 2022, twenty consecutive patients with LARC have been treated according to study protocol. For each patient, both a VMAT and a PBT treatment plans have been generated and compared pairwise. ResultsDose-volume histogram (DVH) analysis revealed that SCRT with protons significantly reduced radiation dose to pelvic organs at risk including bladder, bones, and bowel in comparison to SCRT with photons. Photon and proton treatment plans had equivalent conformity and homogeneity indexes. ConclusionPreoperative SCRT with protons offers a significant reduction of radiation dose to normal tissues compared with current photon-based radiotherapy technique. Demonstrated dosimetric advantages may translate into measurable clinical benefits in patients with LARC. Clinical implications of the dosimetric superiority of SCRT with protons will be presented in the coming reports from the PRORECT trial.

Short-course radiotherapy as part of total neoadjuvant therapy for locally advanced rectal cancer – a new standard?

Selection of optimal perioperative treatment for rectal cancer remains a subject of controversy. Recently established new rationales for the use of short-course preoperative radiotherapy (SCRT – 25 Gy in 5 fractions), instead of standard long-course preoperative radio-chemotherapy (LCRT-CT), are presented and discussed in the present review. New data suggest that short-course radiotherapy combined with 6 cycles of CAPOX, or 9 of FOLFOX4, at present may be considered the best option for perioperative treatment of high-risk rectal cancer. However, there is a clear need to further optimize preoperative treatment using rapidly evolving markers of treatment response, including microsatellite instability and targetable or predictive tumour mutations.

Laparoscopic extralevator abdominoperineal excision in distal rectal cancer patients: a retrospective comparative study

At present, abdominoperineal excision with neoadjuvant chemoradiotherapy (nCRT) is one of the treatment modalities of distal rectal cancer. Our study analyzed the effects of laparoscopic extralevator abdominoperineal resection (ELAPE) compared with laparoscopic conventional abdominoperineal resection(cAPR) in the treatment of distal rectal cancer. Retrospective analysis was conducted on the clinicopathological data of 177 distal rectal cancer patients treated with a laparoscopic abdominoperineal resection between 2011 and 2018. The patients were divided into four groups as follows: ELAPE without nCRT (group A), cAPR without nCRT (group B), ELAPE with long-course nCRT (group C) and cAPR with long-course nCRT (group D). Positive circumferential resection margin (CRM), local recurrence rate, 3-year disease-free survival (DFS) and 3-year overall survival (OS) did not differ between group A and group B. The rate of positive CRM in group C was lower than group D (4.4% vs. 11.9%, respectively), although the difference was not significant (P = 0.377). The 3-year local recurrence rate in group C was lower compared with group D (6.6% vs. 16.7%, respectively), although the difference was not significant (P = 0.135). Three-year DFS and 3-year OS were not different between groups C and D. This study showed that the effect of laparoscopic ELAPE in patients with low-risk rectal cancer is similar to laparoscopic cAPR, revealing that laparoscopic cAPR can be routinely selected for patients with low-risk rectal cancer. Furthermore, laparoscopic ELAPE has a tendency to reduce the rate of positive CRM and local recurrence in patients with high-risk rectal cancer. Laparoscopic ELAPE can be routinely considered for patients with high-risk rectal cancer.

Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial

PurposeTo evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT).MethodsThe primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration.ResultsEighteen patients (13 males, 5 females; median age 55 years [range, 41–77 years]) were enrolled in the trial. Patients underwent surgical resection at 8–9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal–Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT.ConclusionsOur results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.

Updated analysis of a prospective, randomized, controlled trial on the impact on clinical outcomes of fish oil supplementation during neoadjuvant chemoradiation for rectal cancer.

e15594 Background: The intake of nutritional supplements, such as fish oil, can modulate the inflammatory response and thus interfere with therapeutic results. Methods: Patients clinically staged as T3,4 and / or N + rectal adenocarcinoma were randomized 1:1 to receive oral ingestion four capsules, totaling 4g of concentrated fish oil (each gram of fish oil concentrate contained 1448 mg of Eicosapentaenoic acid (EPA) + 964 mg of docosahexaenoic acid (DHA)) throughout neoadjuvant conventional chemoradiation (intervention group – IG) or chemoradiation without supplement (control group – CG). All patients were operated about 8 weeks after chemoradiation. Correlation of inflammatory response - Glasgow Prognostic Score (GPS) with disease-free survival (DFS) was the primary outcome; measurements were collected at 4 moments: M1: at diagnosis; M2: at the end of chemoradiation; M3: at 4 weeks after end of chemoradiotherapy; and M4: preoperatively. Results: From January, 2015 and July, 2017, a total of 111 patients with cT3, 4 and / or N (+) rectal adenocarcinoma were accrued and randomized; 105 were randomized (IG: 51 and CG: 54). Mean age were 60 years, ranging from 30-86 years. There was no difference between groups in M1. In M2 and M3 there were differences between the IG and the CG in systemic inflammatory response measured by GPS (M2: p = 0.001; M3: p = 0.027). After neoadjuvant therapy, 49 patients in the CG and 46 patients in the IG were submitted to surgery; complete pathological response (pCR) was present in 15 patients in the CG and in 10 patients in the IG; there was no association of pCR and fish oil supplementation (P = 0.34). Median follow-up time was 45 months (range: 2-72). With a median follow up time of 24 months, DFS was shorter in patients with KPS &lt; 90% (47.0% vs 80.1%, P = 0.01), high risk (T4 or N+) rectal cancer (67.4% vs 89.7%, P = 0.01) and patients who did not achieve pCR after neoadjuvant CRT (65.5% vs 95.8%, P = 0.003). Also, shorter DFS was observed in patients with GPS 1 or 2 in M2 (69.1% vs 76.7%, p = 0.01) and M4 (38.9% vs 75.3%, p = 0.04) compared to patients with GPS 0 (reduced inflammatory response). In multivariate analysis, patients with high risk rectal cancer and GPS 1 or 2 in M2 had 3.07 and 2.11-fold greater risk of disease relapse; patients who achieved pCR had 84% reduction risk of DFS. KPS and GPS in M4 were not independent prognostic biomarkers for DFS. Conclusions: The oil fish supplementation during neoadjuvant chemoradiotherapy for rectal cancer was able to reduce the systemic inflammation syndrome (GPS = 0) associated with cancer. This reduction during treatment, especially in the preoperative moment was associated with better DFS. Thus, this intervention proposed in our study, as it is easily accessible and low cost, may be a viable strategy in this population and this finding should be better evaluate in future trials. Clinical trial information: NCT02534389.

Personalised care for high-risk rectal cancer: does one size fit all?

Since 2020, the National Institute for Health and Care Excellence (NICE) guidelines have been used in the UK, recommending neoadjuvant radiotherapy for all patients with rectal cancer, except for those with radiologically staged T1–2, N0 tumours. Assessment of the 2020 NICE criteria for preoperative radiotherapy in patients with rectal cancer treated by surgery alone in comparison with proven MRI prognostic factors: a retrospective cohort studyCompared to previous guidelines, implementation of the 2020 NICE guidelines will result in significantly more patients receiving preoperative radiotherapy. High-quality MRI selects patients with good outcomes (particularly low local recurrence) without radiotherapy, with little margin for improvement. Overuse of radiotherapy could occur with this unselective approach. The high-risk group, with the most chance of benefiting from preoperative radiotherapy, is not well selected on the basis of NICE 2020 criteria and is better identified with proven MRI prognostic factors (extramural venous invasion, tumour deposits, and circumferential resection margin). Full-Text PDF Open Access

Induction Chemotherapy and Chemoradiotherapy Combined to ASA vs. Placebo for High-Risk Rectal Cancer: Results of a Randomized Trial

Inductionchemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response. MethodsSingle-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS. ResultsBetween January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%. ConclusionThere was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.