Long-course Chemoradiotherapy Research Articles

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.

Neoadjuvant treatment of colorectal cancer: comprehensive review.

Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery. A narrative review of the most recent relevant literature was conducted. Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients. Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, distant tumor recurrence remains a concern, prompting the exploration of total neoadjuvant therapy (TNT) as a comprehensive treatment strategy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Nonoperative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving complete clinical response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for the assessment of treatment response. This review synthesizes current evidence on TNT, ICIs, NOM, and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

Image-based consensus molecular subtyping in rectal cancer biopsies and response to neoadjuvant chemoradiotherapy

The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine. DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n = 1057 WSIs) with paired transcriptional data. Classifiers were tested on a held out RC biopsy cohort (ARISTOTLE) and correlated with pCR to LCRT in an independent dataset merging two RC cohorts (ARISTOTLE, n = 114 and SALZBURG, n = 55 patients). DL models predicted CMS with high classification performance in multiple comparative analyses. In the independent cohorts (ARISTOTLE, SALZBURG), cases with WSIs classified as imCMS1 had a significantly higher likelihood of achieving pCR (OR = 2.69, 95% CI 1.01–7.17, p = 0.048). Conversely, imCMS4 was associated with lack of pCR (OR = 0.25, 95% CI 0.07–0.88, p = 0.031). Classification maps demonstrated pathologist-interpretable associations with high stromal content in imCMS4 cases, associated with poor outcome. No significant association was found in imCMS2 or imCMS3. imCMS classification of pre-treatment biopsies is a fast and inexpensive solution to identify patient groups that could benefit from neoadjuvant LCRT. The significant associations between imCMS1/imCMS4 with pCR suggest the existence of predictive morphological features that could enhance standard pathological assessment.

Total neoadjuvant therapy for locally advanced rectal cancer: a three-group propensity score matched study

PurposeTotal neoadjuvant therapy (TNT) has emerged as a therapeutic approach for locally advanced rectal cancer (LARC). However, the optimal chemotherapy cycles within TNT remain uncertain. This study aimed to evaluate and compare the prognostic efficacy of varying cycles of chemotherapy during TNT for LARC.MethodsPatients diagnosed with LARC (T3-4N0M0/T1-4N1-2M0), who underwent TNT or chemoradiotherapy followed by total mesorectal excision (TME) between 2015 and 2020, were retrospective included. Patients were categorized into three groups based on their neoadjuvant strategy: CRT (long-course chemoradiotherapy), STNT (long-course CRT with one to three cycles of chemotherapy), and LTNT (long-course CRT with four or more cycles of chemotherapy). Propensity score matching (PSM) based on gender, age, body mass index, tumor distance from the anal verge, clinical T stage, clinical N stage, and mesorectal fascia status was employed to reduce confounding bias. Primary endpoints were disease-free survival (DFS) and metastasis-free survival (MFS).ResultsThe study comprised 372 patients, with 73 patients in each group after PSM. Compared with CRT, both STNT and LTNT demonstrated improved DFS (5-year rate: 59.7% vs. 77.8% vs. 76.5%, p = 0.027) and MFS (5-year rate: 65.1% vs. 81.3% vs. 81.4%, p = 0.030). There was no difference in DFS or MFS between STNT and LTNT. These favorable outcomes were consistent among subgroups defined by tumor distance from the anal verge ≥ 5 cm, clinical T3 stage, clinical N positive status, or involved mesorectal fascia.ConclusionCompared to CRT, both STNT and LTNT demonstrated improved DFS and MFS outcomes. Notably, survival outcomes were similar between STNT and LTNT, suggesting that chemotherapy cycles in TNT may not significantly impact survival.

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.

Patterns of care and survival in patients with multifocal glioblastoma: A Danish cohort study

Abstract Background This Danish cohort study aims to (1) compare patterns of care (POC) and survival of patients with multifocal glioblastoma (mGBM) to those with unifocal glioblastoma (uGBM), and (2) explore the association of patient-related factors with treatment assignment and prognosis, respectively, in the subgroup of mGBM patients. Methods Data on all adults with newly diagnosed, pathology-confirmed GBM between 2015 and 2019 were extracted from the Danish Neuro-Oncology Registry. To compare POC and survival of mGBM to uGBM, we applied multivariable logistic and Cox regression analysis, respectively. To analyze the association of patient-related factors with treatment assignment and prognosis, we established multivariable logistic and Cox regression models, respectively. Results In this cohort of 1343 patients, 231 had mGBM. Of those, 42% underwent tumor resection and 41% were assigned to long-course chemoradiotherapy. Compared to uGBM, mGBM patients less often underwent a partial (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2–0.6), near-total (OR 0.1, 95% CI 0.07–0.2), and complete resection (OR 0.1, 95% CI 0.07–0.2) versus biopsy. mGBM patients were furthermore less often assigned to long-course chemoradiotherapy (OR 0.6, 95% CI 0.4–0.97). Median overall survival was 7.0 (95% CI 5.7–8.3) months for mGBM patients, and multifocality was an independent poor prognostic factor for survival (hazard ratio 1.3, 95% CI 1.1–1.5). In mGBM patients, initial performance, O[6]-methylguanine-DNA methyltransferase promotor methylation status, and extent of resection were significantly associated with survival. Conclusions Patients with mGBM were treated with an overall less intensive approach. Multifocality was a poor prognostic factor for survival with a moderate effect. Prognostic factors for patients with mGBM were identified.

Timing of Surgery and Social Determinants of Health Related to Pathologic Complete Response after Total Neoadjuvant Therapy for Rectal Adenocarcinoma: Retrospective Study of National Cancer Database.

Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to evaluate the relationship between the rest period and pCR. This study utilized the National Cancer Database (NCDB) to retrospectively analyze 5997 stage-appropriate RAC cases treated with TNT from 2016 to 2020. The overall pCR rate was 18.6%, with most patients undergoing induction chemotherapy followed by long-course chemoradiation (81.5%). Multivariable logistic regression models revealed a significant non-linear relationship between the rest period and pCR (p = 0.033), with optimal odds at 14.7-15.9 weeks post radiation (odds ratio: 1.49, 95% confidence interval: 1.13-1.98) when compared to 4.0 weeks. Medicaid, distance to the treatment facility, and community education were associated with decreased odds of pCR. Findings highlight the importance of a 15-16-week post-radiation surgery window for achieving pCR in RAC treated with TNT and socioeconomic factors influencing pCR rates. Findings also emphasize the need for clinical trials to incorporate detailed analyses of the rest period and social determinant of health to better guide clinical practice.

Neoadjuvant Short- Vs. Long-Course Radiation for Locally Advanced Rectal Cancer: How to Choose.

Over the past decades, the treatment of locally advanced rectal cancer has evolved dramatically due to improvements in diagnostic imaging, surgical technique, and the addition of radiotherapy and/or chemotherapy. Fractionation of neoadjuvant radiotherapy with or without concurrent chemotherapy remains the subject of discussion and the question multiple recent trials have aimed to answer. In light of recent data and concern for locoregional recurrence, our institution favors long-course chemoradiation in most cases, especially in low-lying primaries, threatened circumferential resection margin, consideration of non-operative management, or if the surgeon has concerns for resectability. Exceptions would include cases of oligometastatic disease planned for metastasectomy in which curative-intent treatment was pursued or if additional factors required a reduction in treatment time.

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.

Findings in magnetic resonance imaging for restaging locally advanced rectal cancer

PurposeWe aimed to assess the prognostic value of restaging magnetic resonance imaging (MRI) in rectal cancer after neoadjuvant therapy and compare long-course chemoradiotherapy (LC-CRT) to short-course radiotherapy with delayed surgery (SCRT-delay).MethodsThis retrospective study included 267 patients with locally advanced rectal cancer (LARC) operated on between January 2016 and April 2019, all of whom received either LC-CRT or SCRT-delay in the neoadjuvant setting. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS) based on radiological response assessed using the magnetic resonance tumor regression grade (mrTRG).ResultsIn the LC-CRT group, cumulative 1-, 3-, and 5-year OS rates were 94.8%, 86.4%, and 79.0%, while in the SCRT-delay group, they were 83.3%, 68.9%, and 68.9% (P = 0.017). For CSS in the LC-CRT group, cumulative rates were 96.9%, 90.3%, and 85.0%, and in the SCRT-delay group, they were 88.6%, 81.4%, and 81.4% (P = 0.222). There were no significant differences in total histological response rates or local recurrence rates between the treatment groups. The good and moderate response group (mrTRG 1–3) had significantly better cumulative 1-, 3-, and 5-year OS and CSS compared to the poorer response group (mrTRG 4–5) (P = 0.023 for OS and P = 0.048 for CSS).ConclusionUnfavorable MRI response is a sign of poor prognosis in LARC. SCRT-delay is comparable to LC-CRT concerning the oncological outcome.

Neoadjuvant short-course radiotherapy or chemoradiation plus consolidative chemotherapy followed by radical operation for locally advanced rectal cancer.

Limited evidence compares short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCCRT), both of which are followed by consolidative chemotherapy before radical rectal surgery. We conducted a retrospective cohort study to assess treatment response, survival outcomes, and toxicity in patients with locally advanced rectal cancer. Patients (cT3-4 and/or N+) treated with SCRT or LCCRT, consolidative chemotherapy, or total mesorectal excision between 2013 and 2021 were identified. the cause-specific cumulative incidence of disease-related treatment failure, locoregional recurrence, distant metastases, and overall survival were evaluated using flexible parametric competing risk analysis and Kaplan-Meier methods, adjusted for treatment regimens and clinicopathological factors. A pathological complete response (pCR), tumor downstaging, and toxicity have been reported. Among the 144 patients, 115 (80%) underwent curative rectal surgery. The LCCRT and SCRT groups achieved pCR in 10 (18%) and seven (12%) patients, respectively (odds ratio, 1.68; 95% confidence interval [CI], 0.59-4.78). The adjusted cause-specific hazard ratio for disease-related treatment failure with LCCRT versus SCRT was 0.26 (95% CI, 0.08-0.87). Three-year cumulative probability of disease-related treatment failure was 10.0% and 25.6% for LCCRT and SCRT, respectively. No significant differences in T-downstaging, N-downstaging, significant pathologic downstaging (ypT0-2N0), locoregional failure, distant metastasis, or overall survival were found. Late rectal toxicity occurred in 10 (15%) LCCRT and two (3%) SCRT patients, respectively. LCCRT with consolidative chemotherapy demonstrated improved disease-related treatment failure compared with SCRT, despite higher late rectal toxicity. Further research is needed to assess the long-term oncologic outcomes and toxicity.

Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC): Real-world experience from a tertiary Asian cancer center.

39 Background: Multiple studies of TNT for LARC have shown improved pathological complete response (pCR) rate and disease-free survival (DFS). However, real-world data in Asia is limited. Methods: Patients (pts) diagnosed with LARC at National University Cancer Institute, Singapore were discussed at a multidisciplinary tumor board. Patients were eligible for TNT if they had cT2/3N+ or cT4Nany, threatened circumferential resection margin (CRM) and adequate organ function. TNT protocol was systemic chemotherapy with 5-6 cycles of mFOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) or 3-4 cycles of XELOX (capecitabine, oxaliplatin) followed by short- or long-course chemoradiation (CRT), then 3 cycles of mFOLFOX6 or 2 cycles of XELOX. Clinical outcomes included rates of clinical complete response (cCR), pCR, surgery type, R0 resection and DFS. Baseline pt demographics, laboratory results and tumor characteristics were analyzed against these outcomes. Results: 173/205 pts who were diagnosed with rectal cancer between February 2020 and November 2022 had LARC and 47 received TNT. Median age was 65 (range: 33-79), 68.1% male, 78.7% were Chinese, 19.2% had cT4 tumors, 87.2% node positive and 80.9% had CRM involvement. Median tumor distance from anal verge was 6cm (range: 1-15cm) on colonoscopy and 5cm (range: 2-12cm) on magnetic resonance imaging. 95.7% received XELOX, 87.0% had long-course CRT and 83.0% completed all cycles of systemic chemotherapy and CRT. 44.7% had dose reduction of systemic therapy and 4.3% required emergent surgery due to local complications during TNT. After TNT completion, 7 pts did not pursue surgery – 3 achieved cCR (6.4%) and adopted a watch-and-wait approach, 2 had disease progression (PD), and 2 declined. Of those who underwent surgery, 75.0% had sphincter-preserving surgery and 85.0% achieved R0 resection. 2.1% (n =1) achieved pCR. Rates of tumour regression grade (TRG) 0, 1, 2, 3 were 7.5%, 15.0%, 67.5% and 10.0%, respectively. After a median follow up of 21.7 months (range: 9.3 – 41.6 months), 21.3% (n = 10) had disease recurrence and 14.9% (n=7; 5 from PD, 1 from surgery-related complication, 1 unrelated to treatment) passed away. 1-year DFS rate was 88.7% (95% CI 75.0% - 95.2%). Conclusions: This is the first Asian study reporting real-world data of TNT for LARC since its wide-scale adoption. pCR rates appear lower than reported studies. Understanding the limitation of retrospective studies, further analysis is ongoing to determine if factors other than sequence of modality can contribute to the observed findings.

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.

MRI-detected extramural venous invasion (EMVI) response to long-course chemoradiation (LCRT) versus short-course radiotherapy with systemic chemotherapy (SCRT) in patients with locally advanced rectal cancer (LARC)

MRI-detected extramural venous invasion (EMVI) response to long-course chemoradiation (LCRT) versus short-course radiotherapy with systemic chemotherapy (SCRT) in patients with locally advanced rectal cancer (LARC)

The role of total neoadjuvant therapy in locally advanced rectal cancer: a survey of specialists attending the All-Ireland Colorectal Cancer Conference 2022 including lead investigators of OPRA, PRODIGE-23 and RAPIDO

BackgroundThe treatment of locally advanced rectal cancer (LARC) has evolved following recent landmark trials of total neoadjuvant therapy (TNT)—the delivery of preoperative chemotherapy sequenced with radiation.AimTo assess the preferences of colorectal surgery (CRS), radiation oncology (RO) and medical oncology (MO) specialists attending the All-Ireland Colorectal Cancer Conference (AICCC) 2022 regarding the neoadjuvant management of LARC.MethodsA live electronic survey explored the preferred treatment approach and TNT regimen for early-, intermediate-, bad-, and advanced-risk categories of rectal cancer according to the European Society of Medical Oncology (ESMO) guidelines. The survey was preceded by an update from lead investigators of TNT trials (OPRA, PRODIGE-23 and RAPIDO), who then participated in a multidisciplinary panel discussion.ResultsTen CRS, 7 RO and 15 MO (32 of 45 specialists) participated fully in the survey resulting in a response rate of 71%. Ninety-four percent, 76% and 53% of specialists preferred a TNT approach for patients with advanced, bad, and intermediate-risk rectal cancer, respectively. A consolidation TNT regimen of long-course chemoradiotherapy followed by chemotherapy was the most preferred regimen. Upfront surgery was preferred by 77% for early-risk disease.ConclusionThis survey illustrated the general acceptance of TNT by rectal cancer specialists attending the AICCC as a valuable treatment strategy for higher-risk category LARC. Whilst the treatment of LARC changes, it remains best practice to individualize care, incorporating the selective use of TNT as discussed by an MDT and in keeping with the patient’s goals of care.

Protocol for a national audit of the watch-and-wait approach in patients with rectal cancer in Aotearoa New Zealand: The ACCORD study.

The watch-and-wait approach is increasingly being used in the management of rectal cancer as many patients achieve a clinical complete response after neoadjuvant treatment This national, multicentre, retrospective cohort study aims to understand the use of the watch-and-wait approach in the management of rectal cancer in Aotearoa New Zealand and its associated outcomes. This retrospective cohort study will include patients aged 18 years and over with biopsy proven rectal adenocarcinoma diagnosed between January 2015 and December 2022 who have a clinical complete response following neoadjuvant treatment (including short-course radiotherapy, long-course chemoradiotherapy or total neoadjuvant treatment) and have been managed with a watch-and-wait approach. Data will be collected from centres that manage rectal cancer in Aotearoa New Zealand with the eligible population being identified using data linkage with the National Cancer Registry. This multicentre, national cohort study will investigate the use of the watch-and-wait strategy for rectal cancer in Aotearoa New Zealand. Through novel data linkage approaches, these data and methods will lay the foundation for a future prospective registry and outcome-tracking initiative.

A paradigm shift in the neoadjuvant treatment of rectal cancer: a single-institution real-world cohort study using the COVID-19 pandemic to compare clinical outcomes between long-course chemoradiotherapy and RAPIDO-style total neoadjuvant therapy

A paradigm shift in the neoadjuvant treatment of rectal cancer: a single-institution real-world cohort study using the COVID-19 pandemic to compare clinical outcomes between long-course chemoradiotherapy and RAPIDO-style total neoadjuvant therapy

PP246 Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: A multicenter, randomized controlled trial (SOLAR trial)

PP246 Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: A multicenter, randomized controlled trial (SOLAR trial)

Surgical Outcomes in Total Neoadjuvant Therapy for Rectal Cancer Versus Standard Long-course Chemoradiation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This systematic review and meta-analysis seeks to evaluate the impact of total neoadjuvant therapy (TNT) for rectal cancers on surgical complications and surgical pathology when compared with standard long-course chemoradiotherapy (LCRT). The oncological benefits of TNT are well published in previous meta-analyses, but there is little synthesized information on how it affects surgical outcomes. A recent study has suggested an increase in local recurrence and higher rates of breached total mesorectal excision (TME) plane in TNT patients. This study conformed to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search was performed in Medline (via PubMed), Cochrane databases, EMBASE and CINAHL to identify relevant randomized controlled trials (RCTs) comparing outcomes between TNT and LCRT. Meta-analyses of pooled proportions between TNT and LCRT were performed, comparing primary outcomes of surgical mortality, morbidity and all reported complications; surgical-pathology differences, namely mesorectal quality, R0 resection rates, circumferential resection margin positive rates, and sphincter preservation rates. Death and progression of disease during neoadjuvant treatment period was also compared. Risk of bias of RCTs was performed using the Cochrane risk-of-bias tool by 2 independent reviewers. A total of 3185 patients with rectal cancer from 11 RCTs were included in the analysis: 1607 received TNT and 1578 received LCRT, of which 1422 (TNT arm) and 1391 (LCRT arm) underwent surgical resection with curative intent. There was no significant difference in mortality [risk ratio (RR)=0.86, 95% CI: 0.13-5.52, P =0.88, I2 =52%] or major complications (RR=1.04, 95% CI: 0.86-1.26, P =0.70, I2 =0%) between TNT and LCRT. There was a significantly higher risk of breached TME in TNT group on pooled analysis (RR=1.49, 95% CI: 1.03-12.16, P =0.03, I2 =0%), and on subgroup analysis there is higher risk of breached TME in those receiving extended duration of neoadjuvant treatment (>17 weeks from start of treatment to surgery) when compared with LCRT (RR=1.61, 95% CI: 1.06-2.44, P =0.03). No difference in R0 resection rates (RR=0.85, 95% CI: 0.66-1.10, P =0.21, I2 =15%), circumferential resection margin positive rates (RR=0.87, 95% CI: 0.65-1.16, P =0.35, I2 =10%) or sphincter preservation rates (RR=1.02, 95% CI: 0.83-1.25, P =0.88, I2 =57%) were observed. There was a significantly lower risk of progression of disease to an unresectable stage during the neoadjuvant treatment period in TNT patients (RR=0.60, 95% CI: 0.39-0.92, P =0.03, I2 =18%). On subgroup analysis, it appears to favor those receiving extended duration of neoadjuvant treatment (RR=0.44, 95% CI: 0.26-0.80, P =0.002), and those receiving induction-type chemotherapy in TNT (RR=0.25, 95% CI: 0.07-0.88, P =0.03). TNT increases rates of breached TME which can contribute to higher local recurrence rates. TNT, however, improves systemic control by reducing early progression of disease during neoadjuvant treatment period. Further research is warranted to identify patients that will benefit from this strategy.