This study aims to develop a fully automated VMAT planning program for short-course radiotherapy (SCRT) in Locally Advanced Rectal Cancer (LARC) and assess its plan quality, feasibility, and efficiency.

Thirty LARC patients who underwent short-course VMAT treatment were retrospectively selected from our institution for this study. An auto-planning program for neoadjuvant short-course radiotherapy (SCRT) in LARC was developed using the RayStation scripting platform integrated with the Python environment. The patients were re-planned using this auto-planning program. Subsequently, the differences between the automatic plans (APs) and existing manual plans (MPs) were compared in terms of plan quality, monitor units (MU), plan complexity, and other dosimetric parameters. Plan quality assurance (QA) was performed using the ArcCHECK dosimetric verification system.

Compared to MPs, the APs achieved similar target coverage and conformity, while providing more rapid dose fall-off. Except for the V5Gy dose level, other dosimetric metrics (V25 Gy, V23 Gy, V15 Gy, Dmean, etc.) for the small bowel were significantly lower in the AP compared to the MP (p < 0.001). Additionally, the dosimetric parameters for the bladder, pelvic marrow, and femoral head were also lower in the AP, except for the V25Gy for the bladder. The MUs of the AP were approximately 4% lower than those of the MP. The AP showed high consistency in dosimetric parameters across five organs at risk (OARs).

We developed a fully automated, feasible SCRT VMAT planning program for LARC. This program significantly enhanced plan quality and efficiency while substantially reducing the dose to OARs.

As patients with rectal cancer with clinical complete response (cCR) after neoadjuvant therapy may be safely spared Total Mesorectal Excision (TME), strategies to maximize cCR are needed.

We conducted a single-arm phase II study to determine whether dose-escalated short-course radiotherapy (25 Gy/5 fractions + 5 Gy/1 fraction boost) followed by eight cycles of FOLFOXIRI increased cCR rates among adult patients with > T2N0M0 or low T2N0 rectal cancer.

Between 2020 and 2023, we enrolled 37 patients, of whom 27 (73 %) had at least one high-risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin, positive lateral node). At primary endpoint assessment, nine (24 %) patients had cCR on both endoscopy and MRI, and pursued organ preservation (OP). Fourteen (38 %) patients had cCR only on endoscopy, nine of whom pursued OP. Of the 18 patients who pursued OP, nine had local regrowth at two years from radiotherapy start, with two-year TME-free survival of 26 %. Baseline factors significantly associated with not achieving OP included age < 50 years and T4 disease. At mid-treatment restaging, patients who achieved OP were significantly less likely to have persistent node positivity, EMVI, and endoscopically visible tumor. Grade 3+ adverse events at least possibly attributed to chemotherapy and radiotherapy occured in 51% and 43% of patients, respectively.

Short-course radiotherapy with a boost followed by FOLFIXIRI results in OP in one-quarter of patients with high-risk rectal cancer, with poorer response among younger patients and T4 disease. Mid-treatment response may help guide timely decision-making regarding treatment.

Chemoradiotherapy plus total mesorectal excision has been established as the standard treatment for locally advanced rectal cancer (LARC) and can achieve satisfactory local control. However, systemic control of LARC, especially in patients with risk factors for poor prognosis, is still of concern. As application of total neoadjuvant therapy (TNT) has been proposed as a potential solution, a clearer risk stratification of LARC to guide individual treatment is needed. Combination therapy such as targeted therapy or immunotherapy can be used to increase treatment intensity for high-risk LARC. In this review, we evaluate recent trials of several treatment modalities, specifically focusing on intensified TNT regimens for high-risk LARC with the goal of summarizing optimal clinical strategies and future study designs.

Soft tissue sarcoma is a rare heterogeneous group of tumors made up of over 100 histologic types and subtypes. Expert pathology review is crucial to confirm the correct diagnosis prior to treatment. Multidisciplinary discussion and management at an expert center is strongly recommended given the many nuances of treatment. Wide resection +/- preoperative radiotherapy is recommended in most extremity and trunk wall STS patients, while a minority may also require perioperative medical therapy. Macroscopic complete resection remains the standard of care for retroperitoneal sarcoma patients, with preoperative radiotherapy recommended in selected histologic types.

The individual chemotherapy- and radiotherapy-related toxicities between induction (iTNT) and consolidation total neoadjuvant therapy (cTNT) remain unclear. This network meta-analysis (NMA) comparing iTNT, cTNT, and traditional neoadjuvant chemoradiation (nCRT) evaluated the comparative treatment-related toxicities and compliance of the TNT schemas.

A systematic review of randomized clinical trials and nonrandomized studies of interventions was performed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. A Bayesian NMA was conducted, and odds ratios (OR) with 95% credible intervals (CrI) are reported for all outcomes.

Eighteen studies including 5730 patients were identified. iTNT ranked highest on rate of rectal bleeding (cTNT: OR 0.23 95% CrI 0.05-0.93; nCRT: OR 0.33, 95% CrI 0.09-0.96), proctitis (cTNT: OR 0.2, 95% CrI 0.06-0.55; nCRT: OR 0.2, 95% CrI 0.06-0.51), and postoperative diarrhea (cTNT: OR 0.37, 95% CrI 0.18-0.73; nCRT: OR 0.33, 95% CrI 0.15-0.71); cTNT ranked highest on rate of vomiting (iTNT: OR 0.24, 95% CrI 0.05-0.96; nCRT: OR 0.29, 95% CrI 0.06-0.89) and a higher rate of lymphopenia than iTNT (iTNT: OR 0.56, 95% CrI 0.34-0.99). Radiotherapy compliance was highest in cTNT (iTNT: OR 0.23, 95% CrI 0.05-0.72; nCRT: OR 0.18, 95% CrI 0.04-0.58). There was no difference in overall toxicity and mortality, chemotherapy compliance, and remaining individual system-based toxicities and postoperative complications.

Across all treatment strategies, iTNT had higher radiation-related gastrointestinal toxicities and postoperative diarrhea; cTNT had higher vomiting and lymphopenia rates. While no treatment strategy was superior in chemotherapy compliance, radiotherapy compliance was ranked highest in cTNT.

Rectal cancer management has changed significantly in the last decade with the introduction of total neoadjuvant therapy (TNT), minimally invasive surgery, brachytherapy, and organ preservation. A national survey of intensity modulated radiotherapy (IMRT) was carried out in 2020 to support the development of national Royal College of Radiologists (RCR) guidance, published in 2021. We performed a repeat survey in collaboration with the RCR, to inform iterations of the RCR Guidance and establish treatment patterns across the UK to facilitate future research and development.

A web-based survey was developed and tested by the authors prior to dissemination by the RCR to all UK radiotherapy centres. The repeat survey requested details and strategies of current radiotherapy techniques, including details on setup, doses, organs at risk, peer review, and verification, and asked for the standard management of 5 clinical cases within each multidisciplinary team (MDT) serving that radiotherapy centre. Descriptive statistical analysis was carried out.

In total, 42 of 60 (70%) of the NHS centres across the UK answered the repeat IMRT rectal survey, which reflected 70 MDTs answering the clinical scenarios questions. 100% of centres that responded are routinely using IMRT, with 95% of centres using it in all patients. Variation in treatment delivery has reduced since the previous survey. The greatest difference is still in the use of simultaneous integrated boost and definition of organs at risk. The management for the clinical cases was widely different, with answers generally equally distributed between 2-4 options. The highest-scoring treatment strategies ranged from 24% to 57%.

RCR guidance has helped standardise the delivery of radiotherapy to treat rectal cancer in the UK. The variation in neoadjuvant treatment represents an exciting, evolving time in rectal cancer management. Clinical trials are needed to further homogenise treatment, but a degree of national variation is likely to continue.

The primary objective of this study was to determine the clinical impact of using sigmoid take-off (STO) in the management of rectal cancer. We also evaluated the inter-observer reliability in the identification of STO.

This retrospective study reviewed staging MRI of patients with mid and high-rectal cancers performed between January 2019 and December 2022. The location of the tumour was reclassified based on STO as defined by D'Souza et al. (2018) and compared with the location determined based on distance from the anal verge. The proportions of cases that show a change in tumour location from rectal cancer to sigmoid cancer and the potential change in treatment were noted. The interobserver agreement for the location of STO and the location of tumours from STO was studied among four subspecialised abdominal radiologists.

Out of 134 rectal cancer patients included, STO-based assessment resulted in the reclassification of 13.4% (n=18) cases into sigmoid cancer. There was, however, no change in the stage of cancer. Among these 18 patients, there would have been a change in management in 5 patients had the initial assessment been a sigmoid cancer. There was excellent agreement among the radiologists for measuring the distance of STO from the anal verge (ICC = 0.883, p<0.001) and determining the location of the tumour based on STO (K = 0.82, p<0.001).

Using STO changed the location of tumours in 13.4% of high- and mid-rectal cancers. There was excellent agreement among radiologists regarding determining STO and identifying tumour locations using STO.

Complete resection of advanced rectal cancer is challenging, with local recurrence rates ranging from 4% to 12%. Local recurrence is often categorized as central, anastomotic, or lateral, with lateral lymph node (LLN) metastasis being the primary driver of lateral recurrence. Although preoperative radiotherapy effectively manages nonlateral recurrences, it is less effective for lateral recurrences, and LLN dissection significantly reduces lateral recurrence rates. This study aimed to clarify the clinicopathological characteristics associated with lateral and nonlateral recurrences.

We retrospectively analyzed 232 patients (156 males and 76 females; median age, 64 years) who underwent preoperative radiotherapy followed by curative-intent surgery for clinical T3/4 rectal adenocarcinoma located below the peritoneal reflection between April 2010 and December 2017. In total, 40% of the patients underwent LLN dissection. Univariate and multivariate analyses of clinicopathological data were performed to identify the independent risk factors for lateral and nonlateral recurrences.

Local recurrence occurred in 19 (8%) patients: 7 had lateral recurrence, 13 had nonlateral recurrence, and 1 had both. Multivariate analysis identified mesorectal lymph node metastasis as a significant risk factor for lateral recurrence, whereas positive circumferential resection margin was a significant risk factor for nonlateral recurrence.

The identification of different risk factors for lateral and nonlateral recurrence suggests that lateral recurrence is more strongly associated with lymphatic permeation than nonlateral recurrence. These findings highlight the importance of LLN dissection in minimizing the risk of lateral recurrence.

This network meta-analysis examined the efficacy of different types of neoadjuvant therapy (NAT) for rectal cancer in improving clinical and pathologic outcomes.

PRISMA-compliant systematic review of PubMed and Scopus including only randomized clinical trials comparing two or more NAT regimens for rectal cancer. A network meta-analysis was undertaken for the main outcomes, including pathological complete response (pCR), disease downstaging, R0 resection, permanent stoma, and major adverse effects. Risk of bias was assessed using the ROB-2 tool.

19 randomized controlled trials incorporating 7037 patients (62 % males) were included in the analysis. Compared to standard neoadjuvant chemoradiation (NCRT), consolidation total neoadjuvant therapy (TNT) (OR: 1.82, 95 % CI: 1.46-2.27; p < 0.001) and induction TNT (OR: 1.72, 95 % CI: 1.31-2.26; p < 0.001) had higher odds of achieving pCR. Induction TNT was also significantly associated with higher odds of major adverse effects than was NCRT (OR: 3.14, 95 % CI: 2.50-3.94; p < 0.0001). Compared to NCRT, long course chemotherapy significantly increased the odds of R0 resection (OR: 1.42, 95 % CI: 1.13-1.78; p = 0.002), while consolidation TNT significantly increased organ preservation rates (OR: 2.82, 95 % CI: 1.58-5.05; p < 0.001). Short course radiotherapy doubled the odds of positive circumferential resection margins (CRM) compared to NCRT (OR: 1.99, 95 % CI: 1.11-3.55; p = 0.02).

Consolidation and induction TNT were superior in achieving better pathological outcomes in rectal cancer, offering significant benefits over standard NCRT. However, they were associated with a higher risk of adverse effects. Conversely, short course radiotherapy was linked to higher rates of positive CRM.

Radioresistance is a major clinical challenge and the underlying mechanism has not been thoroughly elucidated. In this study, a radioresistant (RR) cell line is established to explore the transcriptomic signatures of radioresistance in colorectal cancer (CRC). KEGG enriched pathway analysis demonstrated that ferroptosis is inactivated in RR cells. Further detection confirmed that radiotherapy can promote ferroptosis, and ferroptosis inactivation is one of the hallmarks of radioresistance in CRC. What's more, induction of ferroptosis can restore the radiosensitivity of CRC cells. Then, we performed RNA sequencing to compare gene expression between parental and RR cells, and cells pretreated with or without RSL3. Via high-throughput screening, NUPR1 was identified as a potential candidate for ferroptosis-mediated radioresistance in CRC. CRC cells can acquire radiation resistance by NUPR1-mediated ferroptosis suppression in the NUPR1-overexpressing cell line. More importantly, ZZW-115, an NUPR1 inhibitor, can sensitise RR cells to radiotherapy. Overall, our findings identify ferroptosis inactivation linked with resistance to radiotherapy. Besides, NUPR1 can promote radiation resistance by inhibiting ferroptosis, and targeting NUPR1 may be a potential strategy to relieve radioresistance associated with ferroptosis in CRC.

Organ preservation through a watch-and-wait (W&W) strategy has become a viable option for select rectal cancer patients with clinical complete responses (cCR) to total neoadjuvant therapy (TNT). This approach limits the morbidity associated with multimodal treatment. However, the optimal treatment strategy and predictors of treatment response are still unresolved. Rectal cancer incidence is rising, particularly in developing countries, and the disease is a major public health concern in Chile. Prior to the no operation after short-course radiotherapy followed by consolidation chemotherapy in locally advanced rectal cancer (NOAHS-ARC) trial, TNT-based treatments and W&W programs had not been implemented in Chile.

This single-arm, multicenter, phase II prospective trial, conducted in Santiago, Chile, will enroll patients with stage II/III rectal adenocarcinoma. Treatment involves induction short-course radiotherapy (25 Gy in 5 fractions) followed by consolidation chemotherapy (FOLFOX × 9 or CAPOX × 6 cycles). The response will be assessed 4-8 weeks after chemotherapy completion. Patients achieving cCR will be offered W&W, while those with incomplete responses will undergo total mesorectal excision. The primary endpoint is the rate of complete tumor response, combining pathologic complete responses (pCR) and sustained cCR (> 1 year), compared to a matched cohort treated with neoadjuvant chemoradiation alone. The trial aims to recruit 48 patients, assuming a combined pCR/sustained cCR rate of 12%. Quality of life measures will be assessed, and a biorepository of tissue and plasma samples will be established for future research, alongside serial endoscopic and MRI images.

NOAHS-ARC seeks to advance organ preservation strategies in rectal cancer while pioneering TNT and W&W protocols in Chile. The study will also focus on functional outcomes and provide valuable data for improving patient care both locally and globally.

ClinicalTrials.gov identifier NCT04864067. Registered on April 28, 2021.

This article summarizes the French intergroup guidelines regarding rectal adenocarcinoma (RA) management published in September 2023, available on the French Society of Gastroenterology website.

This work was supervised by French medical and surgical societies involved in RA management. Recommendations were rated from A to C according to the literature until September 2023.

Based on the pretreatment work-up, RA treatment was divided into four groups. T1N0 can be treated by endoscopic or surgical excision alone if there is no risk factor for lymph node involvement. For T2N0, radical surgery with total mesorectal excision is recommended, but rectal conservation is possible for small tumors (<4cm) after complete/subcomplete response following chemoradiotherapy. For T12N+ or T3+any N, total neoadjuvant treatment (TNT) followed by radical surgery is the gold standard, but rectal conservation is possible for small tumors after complete/subcomplete response following TNT. T3N2 or T+any N are an indication for TNT followed by radical surgery. Immunotherapy shows promise for dMMR/MSI RA. For metastatic tumors, recommendations are based on less robust evidence and chemotherapy plays a major role.

These guidelines aim at providing a personalized therapeutic strategy and are constantly being optimized. Each case should be discussed by a multidisciplinary team.

With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy (RT), optimal sequencing of RT and systemic therapy in the context of total neoadjuvant therapy (TNT), and considerations for selective omission of RT and surgery for rectal cancer.

The American Society for Radiation Oncology convened a multidisciplinary task force to update 3 key questions that focused on the role of RT for patients with operable rectal cancer. The key questions addressed (1) indications for neoadjuvant RT, (2) selection of neoadjuvant regimens, and (3) indications for consideration of a nonoperative management (NOM) or local excision approach after definitive/preoperative chemoradiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.

For patients with stage II-III rectal cancer, neoadjuvant RT was strongly recommended; however, among patients deemed at lower risk of locoregional recurrence, consideration of omission of neoadjuvant RT was conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery. For patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT, a TNT approach was strongly recommended. Among patients with higher risk of locoregional recurrence, TNT with chemotherapy before or after long-course chemoradiation was strongly recommended, whereas TNT with short-course RT followed by chemotherapy was conditionally recommended. For patients with rectal cancer for whom NOM is a priority, concurrent chemoradiation followed by consolidation chemotherapy was strongly recommended. Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of NOM should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations.

The task force proposed recommendations to inform best clinical practices on the use of RT for rectal cancer with strong emphasis on multidisciplinary care. Future studies should focus on further addressing optimal treatment regimens to allow for more personalized recommendations based on individual risk stratification and patient priorities regarding quality of life.

The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.

Purpose To evaluate the outcomes of patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy (CRT) at a community cancer center.  Methods A retrospective chart review was conducted for patients with biopsy-proven rectal adenocarcinoma treated with CRT between January 2017 and June 2020. Patients were excluded if there was metastatic disease (stage IV) at presentation, if curative resection was not planned, or if they received additional preoperative chemotherapy. Preoperative radiotherapy was typically 50.4 Gy in 28 fractions with concurrent capecitabine chemotherapy, followed by surgery six to eight weeks later. Postoperative adjuvant FOLFOX chemotherapy was typically recommended in suitable patients. Outcomes measured included surgical margin status, pathological complete response (pCR), local recurrence rate, distant metastases, cancer-specific survival, and overall survival. Results A total of 120 patients underwent preoperative CRT during this period. Seven patients did not undergo subsequent surgical resection. The pCR rate was 14%, and R0 resection (negative margins) was achieved in 93% of cases. The cumulative incidence of local recurrence was 6%, and distant metastases developed in 23% of patients. The most common metastatic sites were the liver and lungs. With a median follow-up of 28 months, Kaplan-Meier analyses demonstrated a 78% cancer-specific survival (CSS) and 75% overall survival (OS). Conclusion Preoperative CRT resulted in a 14% pCR rate, which was associated with high R0 (93%) and low local recurrence rates (6%). Distant metastatic recurrence rate remains a concern (23%).

The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both.

The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response.

Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS.

SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.

Total Neoadjuvant Therapy (TNT) is a promising strategy for treating locally advanced rectal cancer (LARC) and has started to replace the traditional neoadjuvant chemoradiotherapy (CRT). This review combines findings from pivotal studies that helped TNT to integrate into clinical practice. It emphasizes the efficacy of TNT in improving the disease-free and metastasis-free survival, pathologic complete response and, according to recent studies, a potential improvement in overall survival when compared to standard CRT. In addition, the review analyzes increased organ preservation by TNT and explores the trend towards personalized medicine with the use of TNT. Additionally, it investigates the possibility of excluding radiotherapy in some subgroups. Future directions include integration of immunotherapy, use of TNT in early-stage disease and determining optimal components of TNT, such as type of chemotherapy and type of radiotherapy.

Adenosquamous Gallbladder Cancers (ASGBC) are rare variety of GBCs. Relative paucity of data with regards to the management of ASGBC exists.

Patients with diagnosis of ASGBC from January 2012 to March 2022 were categorised into 'Early', 'Locally advanced (LA)' and 'Metastatic (M)' ASGBC as per the predefined 'TMH Criteria'.

A total of 196 patients included were categorised into early ASGBC (n = 19,9.7%), LA - ASGBC (n = 53,27%) and M - ASGBC (n = 124,63.3%) with median overall survival (OS) being worst for M - ASGBC (3.9 months) and best for early ASGBC (not reached). The 1-year and 3-year OS of LA-ASGBC patients who underwent surgery was significantly higher than those with non-surgical treatment (72.6%, 35.6% vs 25.1%, 0%, p <0.001). Although, the median OS of resected ASGBC was less as compared to resected gallbladder adenocarcinomas (GBACs) (40.8 vs. 56.1 months), it did not reach statistical significance (p=0.06). However, at higher stages of resected LA - ASGBC (Stage III), the median OS was significantly lower as compared to stage-matched resected GBACs (14.5 vs. 30.1 months, p= 0.006).

Multimodality treatment consisting of margin negative surgical resection with perioperative chemotherapy offers the best chance of long-term survival in ASGBC.

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2-3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences.

To investigate the prognostic value of the pretreatment serum carcinoembryonic antigen (CEA) level in patients with rectal cancer treated by preoperative short-course radiotherapy (SCRT) followed by chemotherapy and delayed surgery.

Two hundred and sixty-six consecutive patients with locally advanced rectal adenocarcinoma without distant metastasis receiving preoperative radiotherapy were enrolled. Group 1 patients (n=144) received long-course radiotherapy (LCRT) with 50.4 Gy in 28 fractions using photon radiotherapy (XRT). Group 2 patients (n=122) received SCRT with 25 Gy in 5 fractions using XRT or proton beam therapy (PBT) followed by chemotherapy and delayed surgery. Pathological complete response (pCR), near pathological complete response (npCR), locoregional recurrence (LRR), distant metastasis (DM), disease-specific survival (DSS) and overall survival (OS) rates were estimated and compared to scrutinize the prognostic significance of factors including CEA level.

In group 1, higher CEA level (≥ 7 ng/mL) was a significant negative prognostic factor of pCR (p = 0.003, OR: 0.133), OS (p = 0.011, HR: 2.999), DM (p = 0.008, HR: 2.569), LRR (p = 0.044, HR: 3.160), and DSS (p = 0.015, HR: 3.273). In group 2, higher CEA level (≥ 7 ng/mL) was a significant negative prognostic factor of pCR (p = 0.002, OR: 0.038), OS (p < 0.001, HR: 44.658), DM (p < 0.001, HR: 8.926), LRR (p = 0.028, HR: 8.570), and DSS (p = 0.001, HR: 43.918). The npCR rates for clinical T4 patients were 6.5% and 22.0% (p = 0.032), in group 1 and group 2, respectively.

This study elucidates the prognostic merit of the pretreatment serum CEA level in patients with rectal cancer treated by either preoperative LCRT or SCRT followed by chemotherapy and delayed surgery.

Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC.

The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate.

From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months.

In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

Recently, neoadjuvant short-course radiation therapy (SCRT) has emerged as a valid treatment option for patients with locally advanced rectal cancer (LARC). We assessed SCRT plans using volumetric-modulated arc therapy (VMAT) with Halcyon and Infinity medical linear accelerators (Linacs) and compared the plan quality and delivery efficiency across all cases. Thirty patients who underwent preoperative SCRT for LARC at the hospital were randomly selected. Treatment plans were designed using the Halcyon and Infinity linac platforms, generating Halcyon VMAT plans (Group H) and Infinity VMAT plans (Group I). The target coverage, organ at risk (OAR) dose distribution, number of monitor units, treatment delivery time, and planning complexity of the two groups were compared and analyzed. Plan quality assurance was performed on the ArcCheck phantom. The overall plan quality regarding target volume and OARs was comparable for plans delivered on Halcyon and Infinity Agility machines, with each platform having advantages. Therefore, both radiotherapy platforms are very good options when selecting which technique to use in the clinic.

We conducted the meta-analysis to compare the therapeutic effects of total neoadjuvant therapy (TNT) based on short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) and long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) according to certain significant randomized controlled trials (RCTs).

The researchers retrieved several databases, including PubMed, Embase, Web of Science, and the Cochrane Library, to collect all the relevant literature published since the establishment of the databases until July 30, 2024, and then screened to determine the qualified literature and extracted the relevant information. Finally, RevMan 5.4 software was utilized to conduct the meta-analysis for determining the 95% confidence interval (CI) and pooled risk ratio (RR). There were 9 study indicators, including the pathologic complete remission (pCR) rate, tumor downstaging rate, R0 resection rate, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), acute ≥3 grade toxicity rate, surgery complication rate, and distant recurrence rate. When moderate, even severe, heterogeneity was found, a random-effect model was applied; otherwise, a fixed-effect model was used for the analysis.

A total of 6 eligible RCTs and 2259 participants were included in this meta-analysis. Compared with the standard LCCRT, TNT treatment on the basis of SCRT/CCT increased the pCR rate significantly [RR = 1.67, 95% CI (1.36, 2.04), P < 0.00001], especially in ≥ 4 cycles of the CCT arm [RR = 1.77, 95% CI: (1.41-2.23), p < 0.00001], and led to a similar tumor downstaging rate [RR = 0.99, 95% CI (0.85, 1.15), P = 0.92]. Moreover, survival outcomes, distant recurrence rate, and surgical indicators were comparable between the two groups.

For LARC patients, the SCRT/CCT regimen not only has a higher pCR rate, equivalent OS, and comparable additional indicators versus standard LCCRT but also shortens the treatment time, costs less, and improves patients' adherence to the innovative anti-tumor therapy; hence, with the concept of acute toxicity control, it could be further widely and safely utilized, especially in resource-limited settings.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024600180.

Hypofractionated radiation therapy regimens should not be used as standard of care for localized soft tissue sarcoma.

The management of locally advanced rectal cancer has changed drastically in the last few decades due to improved surgical techniques, development of multimodal treatment approaches and the introduction of a watch and wait (WW) strategy. For patients with a complete response to neoadjuvant treatment, WW offers an opportunity to avoid the morbidity associated with total mesorectal excision in favor of organ preservation. Despite growing interest in WW, prospective data on the safety and efficacy of nonoperative management are limited. Challenges remain in optimizing multimodal treatment regimens to maximize tumor regression and in improving the accuracy of patient selection for WW. This review summarizes the history of treatment for rectal cancer and the development of a WW strategy. It also provides an overview of clinical considerations for patients interested in nonoperative management, including restaging strategies, WW selection criteria, surveillance protocols and long-term oncologic outcomes.

TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.

While the treatment of locally advanced lower and middle rectal cancer with total mesorectal excision (TME) after neoadjuvant therapy is now well defined, the treatment of locally advanced upper rectal cancer (LAURC) remains controversial. Although most teams and academic societies recommend upfront surgery (US) with partial mesorectal excision (PME), as this appears to be sufficient for these tumors, the literature remains conflicting regarding the additional use of neoadjuvant therapy and TME. Current recommendations for the treatment of LAURC do not reflect actual clinical practice. Notably, there is a paucity of published data specific to the treatment of LAURC since most of the data are from sub-analyses of different cohorts. Another important point responsible for the inconsistent data situation is the fact that the current definition of upper rectal cancer is based on anatomical criteria that are difficult to reproduce and therefore also differ between international professional societies. The aim of this review is to provide a deeper insight into the issues surrounding the treatment of LAURC based on an analysis of the current literature, including anatomic and embryologic data.

For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values.

To study dosimetric effects of leaf positioning errors (LPEs) of the Halcyon(2.0) dual-layer MLC on the long-course chemoradiotherapy (LCCRT) with 45∼50.4 Gy in 25∼28 fractions for rectal cancer. Nine Halcyon(2.0)-based LCCRT plans of rectal cancer were retrospectively involved. Four types of LPEs were introduced: (1) Uniformly distributed dual-layer random LPEs (Dual-R); (2) Proximal-layer systemic LPEs (P-S); (3) Distal-layer systemic LPEs (D-S); (4) Dual-layer systemic LPEs (Dual-S). The sensitivities of D98%, D2% and the Equivalent Uniform Dose (EUD) of PTV to various LPEs were investigated as well as varying ranges of EUDs of OARs. The sensitivities of D98% and EUD of PTV to Dual-R was -0.65%/mm and -0.38%/mm; the sensitivities of both indices to the P-S and D-S were similar to each other, ranging from 1.92%/mm to 2.87%/mm; both indices were more sensitive to the Dual-S and values were 4.97%/mm and 3.84%/mm respectively. The EUD changes of the bladder, and left and right femoral heads were from -13.23% to 14.82%. Single-side systemic LPEs lower than 0.7 mm are acceptable for Halcyon(2.0)-based LCCRT, while dual-layer systemic LPEs lower than 0.4 mm are acceptable, considering relative changes of 2% for D98% of PTV as threshold.

To evaluate efficacy and tolerance of short-course radiotherapy (SCRT) prior to possible chemotherapy (CHT) and surgery in 64 patients with locally advanced rectal cancer, in terms of acute and early late toxicity and survival outcomes with prognostic factors.

Sixty-four patients affected by rectal tumor were treated from 2008 to 2023 radiation therapy, with a total dose of 25 Gy in 5 fractions. The Kaplan-Meier method was used to estimate the rates of overall survival (OS), cancer specific survival (CSS), local control (LC), disease free survival (DFS) and metastasis free survival (MFS). Univariate analysis for prognostic factors was performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios. Toxicity assessment has been considered in acute and in early late for gastrointestinal (GI), genitourinary (GU) districts.

Median follow-up was 49.6 months. The median OS was 65 months with 1-year, 2-year and 5-year OS at 90.6%, 77.7% and 60% respectively. CSS at the 1-year, 2-year and 5-year was 98.3%, 96.2% and 86.2% respectively. LC at 1-year, 2-year and 5-year was 93.4%, 89.4% and 87.2% respectively. DFS at the 1-year, 2-year and 5-year was 93.4%, 89% and 87% respectively. The status of lymph nodes at diagnosis was a prognostic factor in term of LC and DFS. Acute GI toxicity was G1 in 10 (15.6%) patients. Five (7.8%) patients had a G1 acute GU toxicity. Fifteen (23.4%) patients developed chronic GI toxicities.

SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined.

This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS).

Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively.

While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.