Sphincter Preservation Rate Research Articles

Effect of short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy on organ preservation in locally advanced rectal cancer.

We analyzed the effectiveness, safety, and mid-term oncological outcomes of short-course radiotherapy (SCRT) and oxaliplatin-based consolidation chemotherapy in patients with locally advanced rectal cancer (LARC). We retrospectively evaluated 64 patients with LARC who underwent SCRT and tegafox (tegafur-uracil/leucovorin plus oxaliplatin) or mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) consolidation chemotherapy before surgery between January 2015 and December 2020. Tumor response, patient compliance, toxicity, surgical outcomes, overall survival (OS), and disease-free survival (DFS) were analyzed. Sixty-four patients with a mean age of 58.67years (44 males) were included; 48 (75%) had tumors within 5cm of the anal verge. Additionally, 93.8% of the patients underwent at least 2months of chemotherapy, and three required dose reduction. Grade III toxicity occurred in 2 patients, and 10 had a clinical complete response and opted for non-operative management. One patient experienced tumor progression and underwent further treatment without surgery. Among the 53 patients who underwent surgery, 51 (96.2%) had sphincter preservation, 3 had Clavien-Dindo grade III complications, and no mortality occurred. The complete response rate for the entire cohort was 23.4%. Moreover, 47 patients (74.6%) had a neoadjuvant rectal score of < 16 after treatment. After a median follow-up time of 32.01months, 6 (9.3%) had local recurrence, and 17 (26.6%) had distant metastasis. The 3-year OS, DFS and stoma-free rates were 89.5%, 65.5%, and 78.1% respectively. SCRT followed by oxaliplatin-based consolidation chemotherapy is safe and effective for tumor downstaging in LARC, further improving the sphincter preservation rate.

Total neoadjuvant treatment and PD-1/PD-L1 checkpoint inhibitor in locally advanced rectal cancer.

For local advanced rectal cancer (LARC), total neoadjuvant treatment (TNT) has shown more complete response (CR), reduced risk of distant metastasis (DM) and increase of the sphincter preservation rate. Now it is the one and only recommendation for high-risk group of LARC according to National Comprehensive Cancer Network (NCCN) rectal cancer guideline, while it is also preferentially recommended for low-risk group of LARC. TNT is also beneficial for distant rectal cancer patients who have need for organ preservation. Even though the prognostic value of programmed cell death-ligand 1 (PD-L1) in the neoadjuvant chemoradiotherapy (NACRT) of LARC patients is undetermined yet, the combination of NACRT and programmed cell death-1 (PD-1)/PD-L1 antibodies seem bring new hope for mismatch repair proficient (pMMR)/microsatellite stable (MSS) LARC patients. Accumulating small sample sized studies have shown that combining NACRT with PD-1/PD-L1 antibody yield better short-term outcomes for pMMR/MSS LARC patients than historic data. However, ideal total dose and fractionation of radiotherapy remains one of unresolved issues in this combination setting. Thorough understanding the impact of radiotherapy on the tumor microenvironment and their interaction is needed for in-depth understanding and exquisite design of treatments combination model.

Patterns of Care and Outcomes of Rectal Cancer Patients from the Iowa Cancer Registry: Role of Hospital Volume and Tumor Location

BackgroundCentralization of rectal cancer surgery has been associated with high-quality oncologic care. However, several patient, disease and system-related factors can impact where patients receive care. We hypothesized that patients with low rectal tumors would undergo treatment at high-volume centers and would be more likely to receive guideline-based multidisciplinary treatment. MethodsAdults who underwent proctectomy for stage II/III rectal cancer were included from the Iowa Cancer Registry and supplemented with tumor location data. Multinomial logistic regression was employed to analyze factors associated with receiving care in high-volume hospital, while logistic regression for those associated with ≥ 12 lymph node yield, pre-operative chemoradiation and sphincter-preserving surgery. ResultsOf 414 patients, 38%, 39%, and 22% had low, mid, and high rectal cancers, respectively. Thirty-two percent were > 65 years, 38% female, and 68% had stage III tumors. Older age and rural residence, but not tumor location, were associated with surgical treatment in low-volume hospitals. Higher tumor location, high-volume, and NCI-designated hospitals had higher nodal yield (≥ 12). Hospital-volume was not associated with neoadjuvant chemoradiation rates or circumferential resection margin status. Sphincter-sparing surgery was independently associated with high tumor location, female sex, and stage III cancer, but not hospital volume. ConclusionsLow tumor location was not associated with care in high-volume hospitals. High-volume and NCI-designated hospitals had higher nodal yields, but not significantly higher neoadjuvant chemoradiation, negative circumferential margin, or sphincter preservation rates. Therefore, providing educational/quality improvement support in lower volume centers may be more pragmatic than attempting to centralize rectal cancer care among high-volume centers.

Factors predicting successful resolution and long-term outcomes of benign anastomotic strictures following rectal cancer surgery

AimAlthough advances in treatment have improved sphincter-preservation rates in rectal cancer, the incidence of benign anastomotic strictures has also increased. This retrospective single-institution study sought to determine the incidence of benign anastomotic strictures and the factors associated with their successful resolution following treatment. MethodologyFrom January 2010 to December 2019, consecutive patients undergoing endoscopic dilatation and/or surgery for benign anastomotic strictures developing after radical sphincter-sparing resections for rectal cancer were evaluated. To model the relationship between outcomes and potential independent variables, sequential univariate and multivariate analyses were performed using binary logistic regression. ResultsOf 2069 rectal cancer patients undergoing sphincter-preserving surgery, benign anastomotic strictures were identified in 110 (5.3%). Mean age was 48.2 ± 13.98 years; 73.6% were male. Distal tumor-extent was within 6 cm of the anal verge in 60%; 80.9% patients received neoadjuvant radiotherapy. Surgical approach in 71.8% was open, 74.5% being anterior or low anterior resections and 70.9% of anastomoses stapled. Covering stoma was performed in 91.8%. On follow-up, strictures of median length 4 cm were identified at median 3 cm from the anal verge. Endoscopic dilatation was offered in 89.1%, whereas 9.1% required redo-surgery. Overall, 49.1% experienced sustained stricture-resolution with dilatation and 45.4% required re-intervention. At last follow-up, 72.7% were stoma-free. On multivariate analysis, good performance status, absence of anastomotic leak, and short-segment strictures predicted successful stricture-resolution. ConclusionEndoscopic dilatation is an effective first-line therapy, with redo anastomosis used to salvage those failing conservative measures. Adverse performance status, anastomotic leak and greater stricture length may predict detrimental outcomes in terms of stricture resolution.

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image-guided intensity modulated radiation therapy in locally advanced rectal cancers.

155 Background: The paradigm of locally advanced (T3/4; T1-4N1-2) rectal cancers (LARC) requires an intensified treatment for better pathological outcomes. Treatment intensification may be done by radiation dose escalation of long course neoadjuvant chemoradiation therapy (NACRT) by image guided Intensity Modulated Radiation Therapy (IG-IMRT) to increase downstaging with potentially higher local control rates. We aimed to analyze the efficacy and safety of NACRT with dose escalated IG-IMRT in LARC. Methods: 20 patients of LARC were recruited in this prospective interventional phase-II study treated by IG-IMRT with 45 Gray/25 fractions to elective nodal volumes and concomitant boost of 55 Gray/25 fractions to gross primary and nodal disease with concurrent capecitabine (825 mg/m2 twice a day on radiation days). All were planned to undergo definitive surgery 6-8 weeks post completion of NACRT with Total mesorectal excision by Low anterior resection (LAR) or Abdominoperineal resection (APR) followed by 6-8 cycles of adjuvant chemotherapy. Post operative response assessment was assessed by Modified Ryan’s scheme for regression and by tumor downstaging. Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Of 20 patients, 18 underwent definitive surgery and received full course adjuvant chemotherapy (90%). Median follow up was 15.1 months. 2 patients refused surgery, had complete clinical response (cCR) on assessment and were on follow up. Tumor downstaging was achieved in 14 (77.7%) patients and nodal downstaging was achieved in 15/18 (83.3%) patients. In 4 patients (22.2%) pCR was achieved and overall complete response (OCR defined as pCR and nearCR, including 2 patients with cCR) in 10 patients (50%). 4 patients planned for APR underwent LAR achieving a sphincter preservation rate of 22%. Grade 3 toxicities were observed in 2 patients which resolved on first follow up. No Grade 4 acute toxicities were reported. No loco-regional relapses were found and all patients are disease free at the time of last follow up. Conclusions: Dose escalation with IG-IMRT offers higher rates of pCR and OCR with acceptable toxicity profile and excellent short term locoregional control. [Table: see text]

A Comparison of Standard Neoadjuvant Long-Course Chemoradiotherapy and Near-Total Neoadjuvant Therapy in Rectal Cancer: A Matched Pair Analysis at Equal Time Interval

<h3>Purpose/Objective(s)</h3> To investigate the efficacy of neoadjuvant chemotherapy administration following standard long-course chemoradiotherapy (LCCRT) before surgery (near-TNT), and to compare the outcomes with standard LCCRT in locally-advanced rectal cancer. <h3>Materials/Methods</h3> A total of 156 patients with cT3-4, cN0-2 rectal adenocarcinoma were included in this retrospective analysis, comprised of 79 patients treated with near-TNT, and 77 patients treated with LCCRT. Near-TNT defined as the incorporation of fluoropyrimidine plus oxaliplatin-based chemotherapy into the 12 weeks period between LCCRT and surgery. The patients treated with near-TNT and LCCRT were matched for cTNM stage at the same institution. The primary aim was to compare the pathologic complete response (pCR), and the secondary end-points were to compare the sphincter preservation and toxicity and safety of the treatments. <h3>Results</h3> A pCR was achieved in 40 of 156 patients (25.6 %) in the total population. The pCR were 24,1 % and 27,3 % with near-TNT and LCCRT, respectively (p=0,781). There was also no significant difference between near-TNT and LCCRT in term of sphincter preservation rate (65.8 % with near-TNT and 71.4 with LCCRT, p=0.561). The median tumor size was 2.5 cm (range: 0.2-10) after LCCRT, and 1.5 cm (range: 0.1-8) after near-TNT (p<0,001). Although near-TNT resulted in increased chemotherapy-related toxicity (p<0001), the treatment did not lead increased postoperative complications. When the groups compared with the Clavien-Dindo score, near-TNT group showed better postoperative complication rates (p=0,008). Additionally, near-TNT group exhibited better postoperative duration of hospitalization (p=0.002). <h3>Conclusion</h3> Though the addition of chemotherapy between the time interval of LCCRT and definitive surgery did not lead pCR rates, it might induce better tumor downsizing together with a cost of treatment-related toxicities. Besides downsizing effects, a positive postoperative complication rates make near-TNT as a potential treatment-approach in locally-advanced rectal cancer.

Locally advanced rectal mucinous adenocarcinoma: is preoperative radiation necessary?

Neoadjuvant chemoradiotherapy is recommended for locally advanced rectal cancer, allowing preoperative down-staging of the primary tumor to facilitate complete surgical removal. However, further investigation is warranted for identifying whether radiotherapy is necessary for rectal mucinous adenocarcinoma (RMAC). Thus, this study was designed to explore the relationship between mFOLFOX6 with or without preoperative radiotherapy and therapeutic efficacy in locally advanced RMAC. A total of 81 patients were retrospectively enrolled, with MRI-defined clinical stage II/III RMAC received neoadjuvant treatment with mFOLFOX6 alone (group A) or mFOLFOX6 plus radiation (group B), followed by total mesorectal excision. Tumor down-staging and tumor response were assessed based on post-treatment MRI-defined radiographical and pathological findings. Follow-up data were retrieved, and the Kaplan-Meier curve was used to determine the relationship between the 3-year disease-free survival (DFS) and overall survival (OS) in the two groups. There were no significant differences in the clinical baseline characteristics of patients between group A and group B. The sphincter preservation rate in group B was 60.9%, higher than in group A (20.0%) (P=0.031). The rate of pathological complete response (pCR) was 14.0% in group B, while no patients had pCR in group A (P=0.029), and the tumor response rate in group B was higher than in group A (52.0% vs. 16.1%, P=0.001). The 3-year probability of OS in group A and B was 77.4% and 72.0% (P=0.509), and 3-year DFS was 58.1% and 56.0% (P=0.592), respectively. Neoadjuvant mFOLFOX6-based chemoradiotherapy could be a promising therapeutic option for patients with RMAC, which was associated with a high rate of pCR and sphincter preservation in comparison to treated with mFOLFOX6 alone.

Short-term Outcomes of Laparoscopy-Assisted vs Open Surgery for Patients With Low Rectal Cancer

The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established. To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer. This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022. Eligible patients were randomized to receive either laparoscopic or open surgery. The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality. A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days. In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery. ClinicalTrials.gov Identifier: NCT01899547.

Impact of neoadjuvant treatment on rectal gastrointestinal stromal tumors.

Although gastrointestinal stromal tumors (GISTs) are rare disease and rectal GISTs is only 5% of total GISTs, they have the worst prognosis. Due to narrow pelvis, tumor rupture or positive resection margin are common in the management of rectal GISTs. The impact of neoadjuvant treatment on the clinical outcomes of rectal gastrointestinal stromal tumors (GISTs) remains unclear. Thus, we conducted a retrospective study to investigate the impact of neoadjuvant imatinib on rectal GIST. The cohort comprised 33 patients; of them, 10 and 23 belonged to the neoadjuvant (i.e., those who underwent neoadjuvant imatinib treatment) and the control group (i.e., those who underwent surgery without prior imatinib treatment), respectively. Neoadjuvant group was associated with more common levator ani muscle displacement (P = 0.002), and showed significantly larger radiologic tumor size (P = 0.036) than the control group. The mean tumor size was significantly decreased after imatinib treatment (6.8 cm to 4.7cm, P = 0.006). There was no significant difference in resection margin involvement (P >0.999), and sphincter preservation rates (P = 0.627) between the two groups. No difference was observed with respect to morbidities, hospital stay, local recurrence and disease-free survival. Neoadjuvant imatinib treated group had similar propensity with control group after treatment. We thought reduced tumor sized could enhance resectability and provide more chance to preserve sphincter for rectal GIST patients. Considering large tumor size and higher rate of sphincter invasion in the neoadjuvant group, imatinib treatment could be helpful as a conversion strategy to make huge and low-lying rectal GIST operable and achieve better surgical outcomes.

EA2201: An ECOG-ACRIN phase II study of neoadjuvant nivolumab plus ipilimumab and short course radiation in MSI-H/dMMR rectal tumors.

TPS3644 Background: Trimodality therapy including chemoradiation, chemotherapy and surgical resection is standard for patients with T3-4 and/or node-positive (N+) rectal adenocarcinomas. Pathologic complete response (pCR) rates after neoadjuvant chemoradiation approach 15% in all-comers and 27% in patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) rectal cancer. Additionally, preclinical data suggest that hypofractionated radiation (large dose per fraction) may enhance immunogenicity. Given high response rates to immunotherapy in MSI-H/dMMR early stage and metastatic colorectal cancer (CRC), we hypothesized that neoadjuvant nivolumab plus ipilimumab and short course radiation in locally advanced MSI-H/dMMR rectal cancer (LARC) would result in increased pCR rates. Methods: EA2201 (NCT04751370) is an NCTN phase II clinical trial for patients with treatment-naïve locally advanced (T3-4Nx or TxN+) rectal adenocarcinoma that is dMMR or MSI-H. Patients receive nivolumab (480 mg) and ipilimumab (1 mg/kg) every 28 days for 2 cycles, followed by short course radiation (5 Gy x 5 fractions; total 25 Gy) and an additional 2 cycles of nivolumab and ipilimumab prior to disease reassessment and TME. The primary endpoint is pCR at TME. Secondary endpoints include 5-year disease-free survival, overall survival, treatment-related toxicities, and sphincter preservation rate for low-lying tumors. This study has a single-arm, two-stage design; a pCR rate of 50% or more will be taken as evidence of promising activity in this patient population. We plan to enroll 31 patients, with accrual currently ongoing. Clinical trial information: NCT04751370.

High dose chemoradiotherapy increases chance of organ preservation with satisfactory functional outcome for rectal cancer

BackgroundHigh dose chemoradiotherapy offers a curative chance for patients with rectal cancer that are unfit or unwilling to undergo surgical resection, yet its long-term survival and functional outcomes have been rarely investigated.MethodsPatients with non-metastatic rectal adenocarcinoma who received pelvic radiation for curative intent from April 2006 to July 2017 were retrospectively investigated. Survival rates were analyzed using the Kaplan–Meier method. Quality of life and functional outcomes were evaluated using the EORTC quality of life questionnaire.ResultsA total of 57 patients were included, with a median age of 59.0 (range, 29–84) years. The numbers of patients who were diagnosed as stage I, II and III were 5 (8.8%), 16 (28.1%) and 36 (63.2%), respectively. 53 (93.0%) patients had tumor located within 5 cm from the anal verge. All patients received fluorouracil-based concurrent chemoradiotherapy with a median radiation dose of 80 (range, 60–86) Gy. All kinds of grade 3–4 adverse events occurred in 18 (31.6%) patients. 42 (73.7%) patients achieved a clinical complete response after chemoradiotherapy. After a median follow-up of 43.5 (range 14.9–163.2) months, 12 (21.1%) patients had local progression and 11 (19.3%) developed distant metastasis. The 3-year local recurrence-free survival and distant metastasis-free survival were 77.3% (95% CI, 65.7–88.8%) and 79.2% (95% CI, 68.2–90.2%), while the 3-year progression-free survival, cancer-specific survival, overall survival were 61.9% (95% CI, 48.8–75.0%), 93.1% (95% CI, 85.8–100.0%) and 91.4% (95% CI, 83.6–99.2%), respectively. For patients who had tumor located within 3 cm from the anal verge, the sphincter preservation rate was 85.3% at last follow-up. Long-term adverse events mainly were anal blood loss. 21 patients completed the quality-of-life questionnaire and had a score of the global health status of 78.57 ± 17.59. Of them, 95.2% reported no urinary incontinence and 85.7% reported no fecal incontinence.ConclusionsHigh dose chemoradiation demonstrated promising survival outcomes with acceptable short-term and long-term side effects, and satisfying long-term functional outcomes and quality of life. It could be considered as a non-invasive alternative for rectal cancer patients who refuse surgery.

Short-term outcomes of robotic-assisted surgery following neoadjuvant chemotherapy for lower rectal cancer.

There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery. From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC. The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P=.024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P < .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P < .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group. Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.

Targeted Radiotherapy Using Contact X-ray Brachytherapy 50 kV.

Simple SummaryOrgan preservation is becoming a topic of great interest for rectal cancer. Radiotherapy, often in association with chemotherapy, is playing a major role in achieving tumor sterilization and long-term local control. In order to achieve this goal, a high dose (>70 Gy) of radiotherapy is necessary. To avoid radiation toxicity of such a high dose, an endocavitary approach using contact X-ray 50 kV brachytherapy (CXB) is an attractive method. Historical series and two randomized trials in Europe give good evidence of the merit of CXB. The selection of early tumors is a key prognostic factor to achieve good results. A planned organ preservation treatment using CXB followed by chemoradiotherapy can be proposed to patients with T2–T3 a–b < 3 cm in diameter. At 3 years, the chance of local control should be close to 90% with good bowel function.Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is an original approach. There are two different ways to perform such an ECB: contact X-ray brachytherapy (CXB) using a 50 kV X-ray generator with an X-ray tube positioned under eye guidance into the rectal cavity and high-dose-rate brachytherapy (HDRB) using iridium-192 sources positioned into the rectal cavity under image guidance. This study focused on CXB. CXB uses a small mobile generator that produces 50 kV X-rays with limited penetration. This technique is well adapted to accessible tumors of limited size and especially needs a high dose rate (≥15 Gy/minutes) for rectal tumors. It is performed on an ambulatory basis. A total dose between 80–110 Gy is delivered in 3–4 fractions over 3 to 6 weeks into a small volume (5 cm3). CXB was pioneered in the 1970s by Papillon using the Philips RT 50TM. Since 2009, the Papillon P50TM has been used in 11 institutions in Europe. The OPERA Phase III trial tested the hypothesis that a CXB boost (90 Gy/3 fr) compared to an EBRT boost (9 Gy/5 fr) for T2–T3 ab < 5 cm and N0–N1 < 8 mm will increase the 3-year organ preservation (OP) rate when combined with 45 Gy/5 weeks with concomitant capecitabine. Out of more than 300 patients with tumors < 3 cm (1962–1992), Papillon reported a long-term local control close to 85%. Similar results were published in Europe and USA at that time. The Lyon R96-2 Phase III trial (2004) demonstrated that, when combined with preoperative EBRT, a CXB boost (90 Gy/3 fr) significantly increased the rate of clinical complete response (cCR) and sphincter preservation, with some patients having OP at 10 years. With more than 2000 patients treated in Europe (2010–2020) using the Papillon 50TM, organ preservation appears possible in close to 80% of cases in selected early T2–T3. The OPERA trial closed after 141 inclusions (2015–2020) after an independent data monitoring committee recommendation because of promising results. At the 2-year follow-up (blinded data), the rate of cCR and OP were 77% and 72%, respectively, for the 141 tumors, and for T < 3 cm (61 pts), they were 86% and 85%, respectively, with good bowel function. The final results should be available in 2022. Organ preservation using NOM appears to be a promising approach for rectal cancer. A CXB boost with chemoradiotherapy in selected early T2–T3 could become an attractive option to achieve a planned OP. This approach should be proposed to well-informed patients after discussion in an MDT.

Responses of Patients with T3-4N0- 2 M0 Rectal Cancer to Preoperative Chemoradiotherapy: Review of Current Literature

Objective: To investigate the efficacy and safety of chemoradiotherapy and radiotherapy followed by surgery in patients with locally advanced unresectable rectal cancer.Material and method: We reviewed records for 65 patients with locally advanced unresectable rectal cancer treated by preoperative chemoradiotherapy or radiotherapy followed by surgery between 2013 and 2016. Of these, 23 patients were treated with preoperative chemoradiotherapy (40 - 45 Gy) plus concomitant chemotherapy (5Fluorouracil + Calcium Folinate). For comparison, 42 similar patients, treated by preoperative radiotherapy (45 - 50Gy) plus surgery served as control. The primary end-point of the study was overall survival and local control rate.Results: No treatment plan was delayed because of toxicities in both groups. The radical resectability rate was 69.9 % in the chemoradiotherapy group and 33.3 % in the radiotherapy plus surgery group (P = 0. 024). The anal sphincter preservation rates were 26. 6 % and 3. 7 %, respectively (P= 0. 028). The anal sphincter preservation rates of the lower rectal cancer were 27. 3 % and 0. 0 %, respectively (P = 0. 014). Response rates of chemoradiotherapy and radiotherapy plus surgery groups were 82.6 % and 61.9 % (P = 0. 053). The tumor downstage rates were 16 (69.6%) and 24 (57.1%) in these groups (P = 0. 206). The 3-years overall survival rates were 66. 7 % and 55. 6 % (P = 0. 485), and the tumor-free survival rates were 40. 3 % and 33. 1 % (P = 0. 663) . The 3-years local recurrent rates were 26. 9 % and 48. 1 % (P = 0. 174) . No obvious late effects were found in either group. Conclusion: The results of this study suggested at least that acute side effects of preoperative chemoradiotherapy can be tolerated and a higher surgical resection rate can be achieved. However, the chemoradiotherapy did not improve the survival rate while it increased local recurrence due to the high rate of anal sphincter preservation. It is safe and effective to use 5-Fluorouracil + Calcium Folinate and 5 – DFUR as a radiosensitizer during the whole course of radiotherapy.

Neoadjuvant PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy in Locally Advanced Anal Canal Squamous Cell Carcinoma Patients: Antitumor Efficacy, Safety and Biomarker Analysis.

BackgroundAnal canal squamous cell carcinoma (ACSCC) is an exceedingly rare malignant neoplasm with challenges in sphincter preservation, treatment toxicities and long-term survival. Little is known concerning the activity of PD-1 antibodies in locally advanced ACSCC. This study reports on the efficacy and toxicities of a neoadjuvant PD-1 blockade combined with chemotherapy followed by concurrent immunoradiotherapy in ACSCC patients, and describes biomarkers expression and mutation signatures.MethodsIn this cohort study, patients were treated as planned, including four cycles of neoadjuvant PD-1 antibody toripalimab combined with docetaxol and cisplatin, followed by radiotherapy and two cycles of concurrent toripalimab. Multiplex immunofluorescence staining (mIHC) with PD-L1, CD8, CD163, Pan-Keratin and DAPI was performed with the pretreatment tumor tissue. Whole exome sequencing was performed for the primary tumor and peripheral blood mononuclear cells. The primary endpoint was the complete clinical response (cCR) rate at 3 months after overall treatment. Acute and late toxicities graded were assessed prospectively.ResultsFive female patients with a median age of 50 years old (range, 43-65 years old), finished treatment as planned. One patient had grade 3 immune related dermatitis. Two patients had grade 3 myelosuppression during neoadjuvant treatment. No severe radiation-related toxicities were noted. Four patients with PD-L1 expression >1% achieved a cCR after neoadjuvant treatment. and the other patient with negative PD-L1 expression also achieved a cCR at 3 months after radiotherapy. All the patients were alive and free from disease and had a normal quality of life, with 19.6-24 months follow up. Inconsistent expression of PD-L1 and CD163 was detected in 3 and 5 patients, respectively. TTN, POLE, MGAM2 were the top mutation frequencies, and 80 significant driver genes were identified. Pathway analysis showed enrichment of apoptosis, Rap1, Ras, and pathways in cancer signaling pathways. Eight significantly deleted regions were identified.ConclusionsThis small cohort of locally advanced ACSCC patients had quite satisfactory cCR and sphincter preservation rate, after neoadjuvant PD-1 antibody toripalimab combined with chemotherapy followed by concurrent immunoradiotherapy, with mild acute and long-term toxicities.

Retrospective study of total neoadjuvant therapy for locally advanced rectal cancer.

Aim: To compare treatment outcomes of total neoadjuvant therapy (TNT) and the standard treatment for locally advanced rectal cancer (LARC). Materials & methods: Patients withLARC(cT2-4 and/or cN1-2) who were treated with preoperative chemoradiotherapy plus induction and consolidation chemotherapy followed by surgery or the standard treatment were recruited. Pathologic complete response (pCR) rate, overall survival, disease-free survival andthe sphincter preservation rate as well as safety were evaluated. Results: 49 cases weretreated with TNT and 71 cases received the standard treatment. Multivariate analysis demonstrated that TNT and tumor size wereindependent risk factors for pCR. Grade 3 chemoradiotherapy toxicity and postoperative complications were similar between the two groups. Conclusion: TNTimproved the pCR rate for patients with LARC, with tolerable toxicities.

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature.

BACKGROUNDThe standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2). AIMTo analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques. METHODSIn December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review. RESULTSThe main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047). CONCLUSIONDose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications.

Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Outcomes of survival, toxicity, sphincter preserving and prognostic factors

BackgroundThis study aimed to compare preoperative chemoradiotherapy (CRT) with postoperative CRT regarding survival, local control, disease control, sphincter preservation, toxicity and also prognostic factors for the treatment of locally advanced rectal cancer. MethodsRecords of 140 patients with locally advanced rectal cancer who received preoperative or postoperative CRT were analyzed retrospectively. We compared the treatment groups (preoperative vs postoperative) according to baseline characteristics (demographic and rectal cancer disease characteristics), and also carried out the survival analyses. ResultsFrom January 2010 to December 2019, 140 patients were included in the analysis, 65 received preoperative treatment and 75 postoperative treatment. There was no difference in survival, recurrence or distant metastasis rate in both treatment groups. The ratios of the failure to complete adjuvant chemotherapy (32% vs 4.6%) and acute grade 3–4 toxicity (32% vs 6.2%) were higher in the postoperative group (p < 0.001). In lower located tumors (≤5 cm from anal verge) the ratio of the sphincter preserving in the preoperative group was 60.7% (n = 17/28), and was 16.6% (n = 3/18) in the postoperative group (Yates χ2 = 5.829, p = 0.005). ConclusionThis study showed no difference in recurrence and survival rate. Preoperative CRT is the preferred treatment for patients with locally advanced rectal cancer, given that it is associated with a superior overall treatment compliance rate, reduced toxicity, and an increased rate of sphincter preservation in low-lying tumors, but not for overall survival.

Impact of preoperative transcatheter rectal arterial chemoembolization with concurrent chemoradiotherapy on surgery and prognosis of patients with locally advanced rectal cancer.

To analyze and evaluate the impact of preoperative transcatheter rectal arterial chemoembolization (TRACE) with concurrent chemoradiotherapy on surgery and prognosis of locally advanced rectal cancer (LARC). A total of 118 patients with LARC were enrolled in this nonrandomized prospective study. They were assigned into the experimental group receiving preoperative TRACE with concurrent chemoradiotherapy (TRACE-CRT group, N = 60) and the control group receiving only neoadjuvant chemoradiotherapy (CRT group, N = 58). All patients underwent surgery after their preoperative treatments. All patients successfully completed the surgical operation. No significant differences were found in sphincter preservation rate and R0 resection rate between TRACE-CRT group and CRT group (p > 0.05). No significant differences were found between the two groups in terms of the perioperative indicators and postoperative complications except mean operation time (165.8 vs. 196.6 min, p < 0.001). Local recurrence occurred in 8 and 5 patients, respectively (p > 0.05). Distant metastasis occurred in 5 and 11 patients, respectively (p < 0.05). Adding TRACE in the preoperative standard treatment for LARC did not increase perioperative complications. In addition, it has the potential advantage of preventing distant metastasis. It is worthy of further application and promotion in clinical practice.

Tolerability and safety of adjuvant chemoradiotherapy with S-1 after limited surgery for T1 or T2 lower rectal cancer.

Chemo-radiotherapy (CRT) after local excision for pT1 with high-risk features or pT2 rectal cancer is recommended as an optional treatment to achieve both curability and maintenance of quality of life. The aim of this study was to evaluate the short-term safety of combining limited surgery with adjuvant CRT for T1 or T2 lower rectal cancer. This was a multicenter, single-arm, prospective phase II trial. Patients diagnosed with lower rectal or anal canal cancer (clinical T1 or T2 with a maximum diameter of 30mm and N0 and M0) underwent local excision or endoscopic resection. Patients received CRT with S-1 (tegafur/gimeracil/oteracil) after confirmation of well- or moderately differentiated adenocarcinoma, and negative margins, and/or depth of submucosal invasion ≥ 1000µm or muscularis propria, and/or positive lymphovascular invasion, and/or tumor budding grade of 2/3. The primary endpoint was relapse-free survival. Secondary endpoints included overall and local relapse-free survival, safety, anal sphincter preservation rate, and anal function. Pathological diagnosis was T1 in 36 patients and T2 in 16 patients. Serious complications after surgery were not reported. The CRT completion rate per protocol was 86.5% (45/52). Thirty-two patients developed 54 events of CRT-related adverse events, including only one patient with a grade 3 event (stomatitis). The most common CRT-related adverse event was diarrhea (n = 14). No patients showed deterioration of anal function at 3years postoperatively. CRT with S-1 after limited surgery for T1 or T2 lower rectal cancer resulted in a low incidence of toxicities and maintenance of anal function.