Radiotherapy For Rectal Cancer Research Articles

Necessity of external iliac lymph nodes and inguinal nodes radiation in rectal cancer with anal canal involvement

Background and purposeWe aimed to explore the necessity of the external iliac lymph nodes (EIN) along with inguinal nodes (IN) region in clinical target volume (CTV) for rectal carcinomas covering the anal canal region.Materials and methodsThis research premise enrolled 399 patients who had primary low rectal cancer detected below the peritoneal reflection via magnetic resonance imaging (MRI) and were treated with neoadjuvant radiotherapy (NRT), without elective EIN along with IN irradiation. We stratified the patients into two groups based on whether the lower edge of the rectal tumor extended to the anal canal (P group, n = 109) or not (Rb group, n = 290). Comparison of overall survival (OS), locoregional recurrence-free survival (LRFS), disease-free survival (DFS), as well as distant metastasis-free survival (DMFS) were performed via inverse probability of treatment weighting (IPTW) along with multivariable analyses. We compared the EIN and IN failure rates between the two groups via the Fisher and Gray’s test.ResultsP group showed a similar adjusted proportion along with five-year cumulative rate of EIN failure compared with the Rb group. The adjusted proportion and five-year cumulative rate of IN failure in the P group was higher in comparison to the Rb group. There were no remarkable differences in the adjusted five-year OS, DFS, DMFS or LRFS between the two groups. Anal canal involvement (ACI) exhibited no effect on OS, LRFS, DFS, or DMFS.ConclusionsDuring NRT for rectal cancer with ACI, it may be possible to exclude the EIN and IN from the CTV.

The in-silico feasibility of dose escalated, hypofractionated radiotherapy for rectal cancer

Background and purposeShort course radiotherapy (SCRT) has a low biological prescription dose. Rectal cancer has a dose response relationship and moderate α/β ratio (∼5). We hypothesise hypofractionated dose escalation has radiobiological advantages. We assessed in-silico dose escalation to the primary tumour using a simultaneous integrated boost (SIB) technique. Materials and methodsPatients who had received 25 Gy/5# were enrolled. GTV was macroscopic tumour including lumen. CTVA was GTV + 10 mm. CTVB included elective nodes. PTV_Low was created from CTVF (CTVA + CTVB) + 7 mm. PTV_High (SIB) was GTV + 5 mm margin. OAR were as per RTOG guidelines. Each patient had 4 plans created at increasing dose levels (27.5 Gy, 30 Gy, 32.5 Gy and 35 Gy) to PTV_High. PTV_Low was 25 Gy/5#.5 test plans were created for each patient in Eclipse™ v15.5 and consisted of 2 VMAT full arcs (6 MV), Varian Truebeam (2.7). Planning objectives were set in the Photon optimiser (PO) and recalculated using Acuros v15.5. A priori feasibility was defined as 90% of plans achieving the planning objectives at 32.5 Gy dose level (EqD2 53.4 Gy). Results20 SCRT patients median age 70, F (n = 5), M (n = 15). Rectum level; low (n = 12), mid (n = 3) and upper (n = 5). 100 plans were analysed. Mean volume of PTV_High was 130 cm3 (SD 81.5) and PTV_Low 769.6 cm3 (SD 241.1). 100% plans complied with mandatory planning dose metrics for each structure at the 25 Gy/5# plan and each dose level. ConclusionHypofractionated dose escalation to the primary tumour up to 35 Gy/5# is technically feasible in rectal cancer radiotherapy.

Curative chemoradiation for low rectal cancer: Primary clinical outcomes from a multicenter phase II trial.

LBA3514 Background: Organ preserving treatment strategies based on chemoradiotherapy may spare rectal cancer patients of major surgery and stoma. We suggest substantially improved tumor control by increasing the radiotherapy dose, without significant increase in the rate of late effects. We designed a prospective phase II trial to test high-dose radiotherapy of low rectal cancer for organ preservation in a multicenter setting. Methods: We enrolled patients with localized T1-3 N0-1 M0 rectal cancer within 6 cm from the anal verge and in performance status 0-2. Any N1-nodes had to be at the level of the tumor and included in the primary tumor-volume. Radiotherapy consisted of 62 Gy to the tumor and 50.4 Gy to the regional lymph nodes, delivered in 28 fractions using intensity modulated radiation therapy and daily image guidance. Capecitabine 825 mg/m2 BID. Patients with clinical complete response (cCR) 6–12 weeks after end of treatment were allocated to follow-up. Surgery was offered only in case of residual cancer or later re-growth. The primary endpoint was the proportion of patients with locoregional tumor control after two years by chemoradiation alone. Secondary endpoints included long-term side effects (CTCAE grading), cCR, rate of distant metastases, and overall survival. Results: Three Danish centers enrolled 107 patients between 2015 and 2019. Baseline classifications were T1/T2/T3 and N1 in 15%/54%/31% and 29%, respectively. The median age was 71 years and 64% were male. 92 (86.0%) had cCR and were allocated to observation. Four patients drew consent or died leaving 103 observed for at least 2 years. 23 had regrowth after cCR, five of whom had organ preserving transanal endoscopic microsurgery, 15 other curative surgery, and three palliation. 63 had no locoregional regrowth. Thus 61% (63/103) of patients with 2 years of follow-up had locoregional tumor control with chemoradiation alone. The actuarial estimate of locoregional control at 2 years from start of observation was 73.8% (95%CI 63.2-81.8). Calculated from time of enrollment, metastasis-free and overall survival at 30 months was 85.4% (95%CI 76.5-91.1) and 94.8% (95%CI 87.8-97.8). In the 63 patients with complete response at 2 years, ‘Low Anterior Resection Syndrome-score’ was None=37%, Minor=28%, and Major=35%. The most severe toxicity was erectile dysfunction grade 3 (n=3), grade 2 (n=4), grade 1 (n=6), and grade 0 (n=26). Grade 2 diarrhea, constipation, fecal incontinence, rectal bleeding and decreased libido were each reported in one case, while urinary frequency grade 2 was seen in four patients. Conclusions: The vast majority of patients with low rectal cancer can be cured by modern radiotherapy 62 Gy in 28 fractions with excellent patient-reported outcomes, toxicity, tumor control, and survival. The treatment is feasible in a multicenter setting. We suggest this approach as a standard of care option. Clinical trial information: NCT02438839.

STAR-TREC phase II: Can we save the rectum by watchful waiting or transanal surgery following (chemo)radiotherapy versus total mesorectal excision for early rectal cancer?

3502 Background: No randomised trials have compared non-operative organ preservation (OP) therapy for early-stage rectal cancer versus standard of care (SoC) using total mesorectal excision (TME) alone. STAR-TREC evaluated the feasibility of recruiting to a study comparing contrasting OP therapies, optimised for treatment of early tumours, versus SoC. Methods: STAR-TREC was a prospective, randomised, open-label, feasibility study in the UK, Netherlands and Denmark. Patients with biopsy proven adenocarcinoma of the rectum, staged ≤mrT3b N0 M0, ≤40mm diameter, ECOG 0-1 were randomised in a 1:1:1 ratio to TME, OP via mesorectal short-course radiotherapy (5x5 Gy), or OP via mesorectal chemo-radiotherapy (25x2 Gy + capecitabine) (Peters FP et al. Mesorectal radiotherapy for early stage rectal cancer: A novel target volume. Clin Transl Radiat Oncol 2020; 21: 104-11). Standardised response assessment classified OP cases as complete response for no further treatment, partial response for transanal endoscopic microsurgery or poor response for TME by 20 weeks. Surveillance following OP consisted of 3-monthly endoscopy/MRI. All cases had CT thorax/abdomen/pelvis at 24 months (m). The primary outcome was recruitment rate over 2 years, with randomisation of 120 international cases calculated as sufficient to support a phase III trial. Secondary outcomes included acute toxicity, stoma and OP rates at 12m, disease free survival (DFS) and non-regrowth DFS (NRDFS) at 24m and EORTC QLQ-C30 summary score at 12 and 24m. Phase II analysis was pre-specified, approved by the data monitoring committee conditional upon grouping of OP arms to inform phase III design, without prejudicing the outcome (STAR-TREC Phase III protocol. Colorectal Disease 2022). Results: Recruitment endpoints were met on 28 Oct 2019. Key secondary outcomes are tabulated by intention to treat. No 6-month mortality occurred. Conclusions: OP pathways optimised for early tumours reduce acute surgical morbidity without introducing substantial radiation toxicity to achieve OP in 60% with no increase in NRDFS at 24m compared to SoC. Overall quality of life was evenly matched. STAR-TREC phase III will determine the optimal strategy for achieving OP (STAR-TREC Phase III protocol. Colorectal Disease 2022). Clinical trial information: NCT02945566. [Table: see text]

Tissue-Based Markers as a Tool to Assess Response to Neoadjuvant Radiotherapy in Rectal Cancer-Systematic Review.

According to current guidelines, the current treatment for locally advanced rectal cancer is neoadjuvant therapy, followed by a total mesorectal excision. However, radiosensitivity tends to differ among patients due to tumor heterogeneity, making it difficult to predict the possible outcomes of the neoadjuvant therapy. This review aims to investigate different types of tissue-based biomarkers and their capability of predicting tumor response to neoadjuvant therapy in patients with locally advanced rectal cancer. We identified 169 abstracts in NCBI PubMed, selected 48 reports considered to meet inclusion criteria and performed this systematic review. Multiple classes of molecular biomarkers, such as proteins, DNA, micro-RNA or tumor immune microenvironment, were studied as potential predictors for rectal cancer response; nonetheless, no literature to date has provided enough sufficient evidence for any of them to be introduced into clinical practice.

Association of the tissue infiltrated and peripheral blood immune cell subsets with response to radiotherapy for rectal cancer

BackgroundTumor microenvironment plays pivotal roles in carcinogenesis, cancer development and metastasis. Composition of cancer immune cell subsets can be inferred by deconvolution of gene expression profile accurately. Compositions of the cell types in cancer microenvironment including cancer infiltrating immune and stromal cells have been reported to be associated with the cancer outcomes markers for cancer prognosis. However, rare studies have been reported on their association with the response to preoperative radiotherapy for rectal cancer.MethodsIn this paper, we deconvoluted the immune/stromal cell composition from the gene expression profiles. We compared the composition of immune/stromal cell types in the RT responsive versus nonresponsive for rectal cancer. We also compared the peripheral blood immune cell subset composition in the stable diseases versus progressive diseases of rectal cancer patients with fluorescence-activated cell sorting from our institution.ResultsCompared with the non-responsive group, the responsive group showed higher proportions of CD4+ T cell (0.1378 ± 0.0368 vs. 0.1071 ± 0.0373, p = 0.0215), adipocytes, T cells CD4 memory resting, and lower proportions of CD8+ T cell (0.1798 ± 0.0217 vs. 0.2104 ± 0.0415, p = 0.0239), macrophages M2, and preadipocytes in their cancer tissue. The responsive patients showed a higher ratio of CD4+/CD8+ T cell proportions (mean 0.7869 vs. 0.5564, p = 0.0210). Consistently, the peripheral blood dataset showed higher proportion of CD4+ T cells and higher ratio of CD4+/CD8+ T cells, and lower proportion of CD8+ T cells for favorable prognosis. We validated these results with a pooled dataset of GSE3493 and GSE35452, and more peripheral blood data, respectively. Finally, we imported these eight cell features including eosinophils and macrophage M1 to Support Vector Machines and could predict the pre-radiotherapy responsive versus non-responsive with an accuracy of 76%, ROC AUC 0.77, 95% confidential interval of 0.632–0.857, better than the gene signatures.ConclusionsOur results showed that the proportions of tumor-infiltrating subsets and peripheral blood immune cell subsets can be important immune cell markers and treatment targets for outcomes of radiotherapy for rectal cancer.

PO-1882 Impact of PTV margin reduction on organ at risk dose in short course radiotherapy of rectal cancer.

PO-1882 Impact of PTV margin reduction on organ at risk dose in short course radiotherapy of rectal cancer.

Colorectal Cancer Develops Inherent Radiosensitivity That Can Be Predicted Using Patient-Derived Organoids.

Analysis of inherent tissue radiosensitivity of patient-derived organoids may provide a readout predictive of neoadjuvant therapy response to radiation in rectal cancer, potentially allowing pretreatment stratification of patients likely to benefit from this approach.

Evaluation of an automated template-based treatment planning system for radiotherapy of anal, rectal and prostate cancer.

The Ethos system has enabled online adaptive radiotherapy (oART) by implementing an automated treatment planning system (aTPS) for both intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) plan creation. The purpose of this study is to evaluate the quality of aTPS plans in the pelvic region. Sixty patients with anal (n=20), rectal (n=20) or prostate (n=20) cancer were retrospectively re-planned with the aTPS. Three IMRT (7-, 9- and 12-field) and two VMAT (2 and 3 arc) automatically generated plans (APs) were created per patient. The duration of the automated plan generation was registered. The best IMRT-AP and VMAT-AP for each patient were selected based on target coverage and dose to organs at risk (OARs). The AP quality was analyzed and compared to corresponding clinically accepted and manually generated VMAT plans (MPs) using several clinically relevant dose metrics. Calculation-based pre-treatment plan quality assurance (QA) was performed for all plans. The median total duration to generate the five APs with the aTPS was 55min, 39min and 35min for anal, prostate and rectal plans, respectively. The target coverage and the OAR sparing were equivalent for IMRT-APs and VMAT-MPs, while VMAT-Aps.demonstrated lower target dose homogeneity and higher dose to some OARs. Both conformity and homogeneity index were equivalent (rectal) or better (anal and prostate) for IMRT-APs compared to VMAT-MPs. All plans passed the patient-specific QA tolerance limit. The aTPS generates plans comparable to MPs within a short time-frame which is highly relevant for oART treatments.

Population-level utilisation of neoadjuvant radiotherapy for the treatment of rectal cancer.

International clinical guidelines recommend long- or short-course neoadjuvant radiotherapy for locally advanced rectal cancer. This study aims to examine variation in the use of neoadjuvant radiotherapy for rectal cancer and identify patient and hospital factors that underpin this variation. We conducted a retrospective, consecutive cohort study using statewide hospitalisation and radiotherapy data from New South Wales, Australia, 2013-2018. Included participants had a primary rectal adenocarcinoma and underwent surgical resection. Factors associated with the use or not of any neoadjuvant radiotherapy, and short versus long-course were explored using multilevel logistic regression models. Of the 2912 people included in the study, 43% received neoadjuvant radiotherapy. There was significant variation in the use of neoadjuvant radiotherapy depending on geographic location. Abdominoperineal excision (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.53-2.28) and having surgery in a public hospital (OR = 2.34, 95% CI = 1.92-2.87) were both predictors of use. Among those receiving neoadjuvant radiotherapy, 17% received short-course therapy, with short-course declining over the study period. The use of neoadjuvant radiotherapy for rectal cancer is highly variable, with differences only partially explained by assessable patient-or hospital-level factors. Understanding neoadjuvant radiotherapy utilisation patterns may assist in identifying barriers and opportunities to improve adherence to clinical guidelines.

Preoperative radiotherapy for rectal cancer: A bibliometric analysis of the 100 most-cited research articles.

Preoperative long-course radio-chemotherapy (LC-RCHT) or preoperative short-course radiotherapy (SC-RT) are widely used in the treatment of locally advanced rectal cancer (LARC). This study aimed to evaluate the 100 most-cited research articles focused on preoperative radiotherapy for rectal cancer to reveal existing academic trends and the direction of therapeutic research. This was a retrospective study based on publicly accessible data. The Web of Science database was used to identify the 100 most-cited articles. The median values for total citation and average citation per year (CPY) were 240.50 (range, 150-3787) and 17.32 (5.03-222.76), respectively. Randomized (median: 24.88 vs 13.32, P = 0.001) and funded (median: 27.33 vs 14.73, P = 0.002) studies had more CPY than those with opposite characteristics. No significant difference was found between studies using SC-RT and LC-RCHT, in terms of average CPY (median: 15.27 for SC-RT vs 18.36 for LC-RCHT, P = 0.303). In terms of the primary aim of the investigation, studies investigating non-operative treatment strategies had higher CPY than those investigating other subcategories (p = 0.029). Randomized studies, funded studies, and studies investigating non-operative treatment were associated with more CPY. There remains equal interest in preoperative SC-RT and LC-RCHT for rectal cancer.

Identifying the long-term survival beneficiary of preoperative radiotherapy for rectal cancer in the TME era

This study was to verify the long-term survival efficacy of preoperative radiotherapy (preRT) for locally advanced rectal cancer (LARC) patients and identify potential long-term survival beneficiary. Using the Surveillance, Epidemiology, and End Results (SEER) database, 7582 LARC patients were eligible for this study between 2011 and 2015 including 6066 received preRT and 1516 received surgery alone. Initial results showed that preRT prolonged the median overall survival (OS) of LARC patients (HR 0.86, 95% CI 0.75–0.98, P < 0.05), and subgroup analysis revealed that patients with age > 65 years, stage III, T3, T4, N2, tumor size > 5 cm, tumor deposits, and lymph nodes dissection (LND) ≥ 12 would benefit more from preRT (all P < 0.05). A prognostic predicting nomogram was constructed using the independent risk factors of OS identified by multivariate Cox analysis (all P < 0.05), which exhibited better prediction of OS than the 8th American Joint Cancer Committee staging system on colorectal cancer. According to the current nomogram, patients in the high-risk subgroup had a shorter median OS than low-risk subgroup (HR 2.62, 95% CI 2.25–3.04, P < 0.001), and preRT could benefit more high-risk patients rather than low-risk patients. Hence, we concluded that preRT might bring long-term survival benefits to LARC patients, especially those with high risk.

Shrinkage of the non-malignant prostate gland volume after receiving incidental radiotherapy for rectal cancer.

BackgroundThe purpose of this study was to assess the impact of coincidental radiotherapy on the volume of the non-malignant prostate gland in rectal cancer patients treated with neo-adjuvant radiotherapy.Materials and methodsIn this retrospective analysis, thirty male patients with rectal cancer who had neoadjuvant radiotherapy met the inclusion criteria. These patients had pre-treatment magnetic resonance imaging (MRI) and at least one post-treatment MRI of the pelvis and the whole of their prostate volume received the full prescribed radiotherapy dose; 45 Gy in 25 fractions (n = 22), 45 Gy in 20 fractions (n = 4) and 25 Gy in 5 fractions (n = 4).ResultsThe median age of this patient cohort was 66 years (range: 30–87). With a median interval between pre-treatment MRI and first MRI post-treatment of 2 months (range: 1–11), the mean prostate volume reduced from 36.1 cm3 [standard deviation (SD) 14.2] pre-radiotherapy to 31.3 cm3 (SD 13.0) post radiotherapy and this difference was significant (p = 0.0004).ConclusionRadiotherapy may cause shrinkage in volume of normal (non-malignant) prostate. Further research is required in this field, since these results may be of some comfort to men contemplating the consequences of radiotherapy on their quality of life. The authors suggest recording flow-rate and international prostate symptom score (IPSS) during rectal radiotherapy as a next step.

Laparoscopic synchronous resection of rectal cancer and liver metastases: A case report and review of the literature.

Introduction and importanceDuring the past decade, there are several studies which showed the advantages of the laparoscopic approach for treating colorectal cancer (CRC) or colorectal cancer liver metastasis (CRCLM). However, in contrast, there are only a few reports of combined one stage synchronous laparoscopic colorectal and liver metastasis resection, cold one stage minimally invasive approach (MIA).Case presentationOur patient was 51 years old woman.Rectal adenocarcinoma was verified three centimeters from the anal verge. Magnetic resonance imaging (MRI) with rectal protocol modification indicated T1N0MO stage. We decided to do transanal local excision and achieved R0 resection. Half a year after the operation on the control MRI, lymphadenopathy was found along the rectum and possible recurrence of cancer. Also on the MRI was shown solitary, 4.7 × 2.7 × 3.8 cm big metastasis in the IVa/VIII segment of the liver. The patient was shown on a multidisciplinary team and it was decided to do laparoscopic synchronous resection of rectum and liver metastases.Clinical discussionDuring the last decades many articles with different strategies for treating CRC and liver metastasis were published. Some of them prefered two-stage surgical treatment, like liver first approach which allows initial control of liver metastases, and delivery of preoperative radiotherapy for rectal cancer without the fear that liver metastases will meanwhile progress beyond the possibility of cure. Alternatively, the colon first approach is where the adjuvant chemotherapy is combined with the resection of the primary colorectal tumour with liver resection being undertaken (if at all) as a subsequent operation. By developing surgery, anaesthesia and critical care, the one stage approach for patients with CRC and liver metastasis started to be a reasonable option.ConclusionTotally laparoscopic synchronous resection of the colorectal cancer and synchronous colorectal liver metastasis is technically feasible and safe in the hands of the experienced abdominal surgeon. This type of approach offers all the benefits of the laparoscopic minimally invasiveness associated with good oncological outcomes, and it is indicated in well-selected patients. However, the real scientific answer to this question can be given just with randomised control trial which will be a real challenge for endoscopic surgeons in the future.

Trends in Staging, Treatment, and Survival in Colorectal Cancer Between 1990 and 2014 in the Rotterdam Study.

BackgroundThis study aims to assess trends in patient-related factors and treatment strategies in Dutch colorectal cancer (CRC) patients and their effect on survival.MethodsData were obtained from the Rotterdam study, an ongoing population-based study of individuals aged ≥45 years. Between 1990 and 2014, incident, pathology-confirmed CRC cases were divided into two groups based on date of diagnosis (either before or after January 1, 2003). Patient characteristics, initial treatment, and date of mortality were collected. Analyses were performed using Kaplan–Meier and Cox proportional hazard models.ResultsOf 14,928 individuals, 272 developed colon cancer and 124 rectal cancer. Median follow-up was 13.2 years. Patients diagnosed after January 1, 2003 were treated chemotherapeutically more often than those diagnosed prior to this date in colon cancer (28.6% vs. 9.1%, p = 0.02) and treated more often with chemotherapy (38.6% vs. 12.3%, p = 0.02) and radiotherapy (41.3% vs. 10.2%, p = 0.001) in rectal cancer. Overall survival, adjusted for patient, tumor characteristics, and treatment, improved in rectal cancer (HR, 0.31; 95% CI, 0.13–0.74) but remained stable in colon cancer (HR, 1.28; 95% CI, 0.84–1.95).ConclusionChemotherapeutic agents and radiotherapy are increasingly used in CRC patients. Survival in rectal cancer improved, whereas in colon cancer this was not observed.

Serial sampling of rectal tumors during radiotherapy: A proof-of-concept study.

153 Background: Treatment response to neoadjuvant therapy in locally advanced rectal cancer (LARC) remains heterogenous. Clinicians are guided by pre-treatment clinical assessment alone in determining neoadjuvant strategy. More must be done to uncover biological mechanisms underpinning response and resistance. We have developed a biospecimen collection protocol in LARC performing serial sampling of tumors and peripheral blood samples prior to, during and after treatment to characterize the biological evolution of this heterogenous response. Here we present early proof of concept results with a focus on the intra-tumoral immune response relating to radiotherapy (RT). Methods: Patients receiving standard-of-care neoadjuvant RT were recruited to an ethically approved study between Dec 2018 - Aug 2021. The protocol consisted of a baseline biopsy and blood sample prior to RT followed by repeat sampling at 2, 6 and 12wks after Day 1 of RT. Standard immunohistochemistry (IHC) was performed for markers of immune activity. Target capture sequencing was performed using RNA baits extracted from serial biopsies to target a 276 genes panel. Paired tumor-normal sequencing was performed. Bulk 3’ RNA seq (Lexogen Illumina Quantseq) characterized immune and inflammatory gene expression. A multiplex bead array (Luminex xPONENT) of 24 cytokines and chemokines was performed using serial plasma samples. Results: 17pts were recruited, 3 with stage IV disease. 14pts received chemoradiation and 3 pts had short-course based regimens. Treatment responses were evaluable in 14pts: graded complete in 2pts; good/ near complete in 7pts and partial/ poor in 5pts. All tumors were MSS, and most frequently mutated genes were APC (75%), KRAS (38%), NRAS (25%) , NOTCH1 (25%) and PIK3CA (25%) (n = 8). Quantseq demonstrated that the immune/ inflammatory response, as measured by interferon-gamma response and IL-6/ JAK-STAT signaling, was significantly elevated up to 12wks after Day 1 RT, with a peak at around 6wks (n = 3). Correlative IHC showed an increase in innate immune cells in pts with a favorable response at 6wks (n = 8). Cytokine/ chemokine analysis suggested patients with a favorable response demonstrated strong inflammatory (MCP1 &amp; IL-17a) responses 2 and 6wks post-RT and strong CTL (Granzyme B) and Th1 (GM-CSF &amp; IP-10) responses 12wks post-RT (n = 10). Conclusions: We show acquisition of meaningful genomic and transcriptomic material from serial biopsies in rectal cancer is possible. Early data suggest that dynamic profiling of rectal tumors demonstrates transcriptomic evolution during treatment. Specifically, we show that the immune response to radiotherapy peaks at around 6wks after initiation of RT and persists to 12wks. This supports ongoing trials of immunomodulatory treatments in combination with, and following, RT in rectal cancer. Further work is required to define differences between responders and non-responders.

Total Mesorectal Excision vs. Transanal Endoscopic Microsurgery Followed by Radiotherapy for T2N0M0 Distal Rectal Cancer: A Multicenter Randomized Trial

IntroductionTransanal endoscopic microsurgery (TEM) is an organ-preserving treatment alternative for patients with early rectal cancer. However, TEM alone is associated with greater risk of local recurrence and inferior survival in comparison with total meso-rectal excision (TME). As an important adjuvant therapy, radiotherapy can effectively reduce the local recurrence rate of rectal cancer. This study aimed to investigate whether TEM followed by radiotherapy can be a valid alternative to TME in T2N0M0 distal rectal cancer treatment.MethodsWe plan to recruit 168 participants meeting established inclusion criteria. Following informed consent, participants will randomly receive treatment protocols of TEM followed by radiotherapy (a total dose of 45–50.4 Gy given in 25–28 factions) or TME. Depending on post-operative pathology, the participants will receive either long-term follow-up or further treatment. The primary endpoint of this trial is 3-year local recurrence rate. The secondary end points include 3-year disease-free survival rate, 3-year overall survival rate, 3-year mortality rate, post-operative quality of life, post-operative safety index, intraoperative evaluation index and post-operative short-term evaluation index.DiscussionThis trial is the first prospective randomized trial to investigate the rectum preserving treatment by using transanal local excision followed by radiotherapy.Clinical trial registrationThe trial was prospectively registered at ClinicalTrials.gov NCT04098471 on September 20, 2019.

Detecting the Research Trends and Hot Spots in External Irradiation Therapy for Rectal Cancer.

Purpose: The aim of this study is to visualize and analyze the research hot pots in radiation therapy for rectal cancer and provide researchers with a clear and visual reference for subsequent studies.Methods: The literature scientometric analysis about “external beam radiation therapy (EBRT) for rectal cancer” was made through the WoSCC (2010 to 2019). And the data was visualized and analyzed by the Microsoft Office Excel (2019) and CiteSpace (V. 5.7.R1).Results: 4,263 relevant articles were downloaded. The number of published articles per year has been increasing (2010-2020). The United States published the highest number of articles. The UK has the strongest partnerships with other countries/regions. Leiden University has the highest number of published articles and University Texas MD Anderson Cancer Center has extensive collaborations with other academic institutions. The number of articles published in the Diseases of the Colon Rectum is the most, and the Journal of Clinical Oncology is the most cited. 27 articles became the strongest burst citations lasting until 2020. In recent years, a lot of research has been done on “watch and wait”, “short-course radiotherapy”, “MRI”, “neoadjuvant radiotherapy, “MRI in rectal cancer”, “chemotherapy regimen improvement”, “adding adjuvant chemotherapy”, and so on.Conclusion: The current research hot pots may be the “watch and wait”, “short-course radiotherapy”, “MRI”, “neoadjuvant chemoradiotherapy”, “MRI in rectal cancer”, “chemotherapy regimen improvement”, and “adding adjuvant chemotherapy”.

A Machine Learning Model of Complete Response to Radiation in Rectal Cancer Reveals Immune Infiltrate and TGFβ Signalling as Key Predictors

A Machine Learning Model of Complete Response to Radiation in Rectal Cancer Reveals Immune Infiltrate and TGFβ Signalling as Key Predictors

A Comprehensive Evaluation of the Application of the Halcyon(2.0) IMRT Technique in Long-Course Radiotherapy for Rectal Cancer.

Objective: To evaluate if the Halcyon(2.0) Intensity Modulation Radiotherapy (IMRT) technique has an advantage in the long-course rectal cancer radiotherapy. Methods: A total of 20 clinical IMRT plans of Halcyon(2.0) for long-course (2Gy in 25 fractions) rectal cancer radiotherapy were randomly selected. Based on the parameters of these plans, 20 TrueBeam (with the Millennium 120 MLC) plans were redesigned, respectively. The dosimetry indexes, field complexity parameters, the Gamma Passing Rates (GPR), and the delivery time of the 2 groups of plans were obtained as measures of the plan quality, the modulation complexity, the delivery accuracy, and the delivery efficiency. The differences between the 2 groups of parameters were analyzed, with P < .05 means statistically significant. Results: In terms of dosimetry, there was no significant or clinical difference between the 2 groups in critical dosimetry parameters. The Monitor Unit of the Halcyon(2.0) fields is lower than the TrueBeam fields by 26.39, while the modulation complexity score (MCS), the mean aperture area variability (AAV), and the mean leaf sequence variability (LSV) of the Halcyon(2.0) fields were 23.8%, 20%, and 2.3% larger than those of the TrueBeam fields, respectively. Neither the ArcCheck-based GPRs nor the portal-dosimetry-based GPRs in both 3%/3 mm and 2%/2 mm criteria showed the difference between the Halcyon(2.0) fields and the TrueBeam fields. The Pearson correlation coefficient between GPR(2%/2 mm) and MCS of the Halcyon(2.0) fields was 0.335, while that of the TrueBeam fields was 0.502. The mean total delivery time of the TrueBeam plans was 195.55 ± 22.86 s, while that of Halcyon(2.0) was 124.25 ± 10.42 s (P < .001), which was reduced approximatively by 36%. Conclusion: For long-course rectal cancer radiotherapy, the Halcyon(2.0) IMRT plans behave almost the same in dosimetry and delivery accuracy as the TrueBeam plans. However, the lower MU and the field modulation complexity, combined with the higher delivery efficiency, make Halcyon(2.0) a feasible and reliable platform in long-course radiotherapy for the rectal cancer.