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Introduction: Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT—whether induction chemotherapy should precede or follow chemoradiotherapy—remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. Methods: Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high‐quality studies, specific inclusion and exclusion criteria were applied. Results: The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO‐12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. Conclusion: This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies. [ABSTRACT FROM AUTHOR]

The treatment of locally advanced rectal cancer (LARC) is a challenging situation for radiation oncologists and colorectal surgeons. Most current approaches recommend neoadjuvant fluorouracil or capecitabine-based chemoradiotherapy followed by surgery as a standard of care. Intensification of concurrent chemotherapy by adding oxaliplatin to fluorouracil or capecitabine backbone to get better outcomes is the matter that has remained unresolved. In this review, we searched Medline and Google Scholar databases and selected 28 prospective phase II and III clinical trials that addressed this question. We discussed the potential advantages and drawbacks of incorporating oxaliplatin into concurrent chemoradiation therapy. We tried to define whether adding oxaliplatin to concurrent chemoradiation with excellent performance and high-risk features benefits some subpopulations. The available literature suggests that by adding oxaliplatin there are some benefits in enhancing response to neoadjuvant chemoradiotherapy, however, without any translated improvements in long-term outcomes including overall and disease-free survival. [ABSTRACT FROM AUTHOR]

Purpose: To identify efficacy, complication, and pathologic response of high-dose-rate endorectal brachytherapy (HDR-BRT) boost in neo-adjuvant chemoradiotherapy (nCRT) of locally advanced rectal cancer. Material and methods: Forty-four patients who met eligibility criteria were included in this non-randomized comparative study. Control group was recruited retrospectively. nCRT (50.40 Gy/28 fr. plus capecitabine 825 mg/m2 twice daily) was administered to both groups before surgery. In the case group, HDR-BRT (8 Gy/2 fr.) was supplemented after chemoradiation. Surgery was done 6-8 weeks after completion of neo-adjuvant therapy. Pathologic complete response (pCR) was the study's primary endpoint. Results: From 44 patients in the case and control groups, pCR was 11 (50%) and 8 (36.4%), respectively (p = 0.27). According to Ryan's grading system, tumor regression grade (TRG) TRG1, TRG2, and TRG3 were 16 (72.7%), 2 (9.1%), and 4 (18.2%) in the case, and 10 (45.5%), 7 (31.8%), and 5 (22.7%) in the control group (p = 0.118). T down-staging was found in 19 (86.4%) and 13 (59.1%) patients in the case and control groups, respectively. No grade > 2 toxicity was identified in both the groups. Organ preservation was achieved in 42.8% and 15.3% in the case and control arm (p = 0.192). In the case group, 8-year overall survival (OS) and disease-free survival (DFS) were 89% (95% CI: 73-100%) and 78% (95% CI: 58-98%), respectively. Our study did not reach median OS and median DFS. Conclusions: Treatment schedule was well-tolerated, and neo-adjuvant HDR-BRT could achieve better T downstaging as a boost comparing with nCRT, without significant complication. However, the optimal dose and fractions in the context of HDR-BRT boost needs further studies. [ABSTRACT FROM AUTHOR]

Tailgut cyst, a type of retro‐rectal cyst, is a rare condition requiring evaluation for malignant transformation. We report a case of squamous cell carcinoma arising in the retro‐rectal cyst, in a 51‐year‐old female who underwent incomplete resection of the cyst and chemo‐radiotherapy, subsequently became locally recurred and metastatic. Malignant transformation of tailgut cysts should be detected. The treatments based on pathology include complete surgical excision with or without chemotherapy and radiotherapy. Our case had a poor outcome despite the multi‐modality treatments. [ABSTRACT FROM AUTHOR]

Rectal cancer is one of the most prevalent cancers in the world. In many countries, the current standard of care is long-course chemoradiation (CRT), followed by total mesorectal excision. Some efforts have been made by intensifying radiation or chemotherapy components of the neoadjuvant therapy to further decrease the local recurrence and augment surgery's feasibility and improve the oncological outcomes. This paper reviews recent intensified neoadjuvant interventions in locally advanced rectal cancer (LARC) in terms of efficacy and treatment-related toxicity. Many maneuvers have been made so far to improve the oncological outcomes of rectal cancer with intensified neoadjuvant longcourse CRT. Some of these approaches seem compelling and deserve further study, while some have just increased the treatment-related toxicities without evident benefits. Those endeavors with greater pathological complete response than the standard of care may make us await the long-term results on survival rates and chronic treatment-related toxicity. After introduction of neoadjuvant CRT for LARC there have been many efforts to improve its outcomes. Here, this study gathered most of these efforts that intensified the neoadjuvant therapy with some being promising and some being futile. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m² from day 1-5 twice daily and oxaliplatin 50 mg/m² on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m² twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment- related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade =3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates. [ABSTRACT FROM AUTHOR]

Background: Colorectal carcinoma is one of most common cancers in Iran with increasing incidence. The mean age of the affected is decreasing. With progresses in multimodality treatment, we witnessed improved prognosis in colorectal cancers. Objectives: This study aimed at evaluating the outcomes of patients with rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy followed by surgery. Methods: In this retrospective cohort study, we assessed the oncologic treatment outcomes of patients with locally advanced (T3-4 or N+ve) rectal adenocarcinoma in our high volume cancer center, Iran cancer institute, Tehran, Iran. Patients with synchronous metastasis, previous malignancy, and history of pelvic radiation were excluded. The primary endpoint was overall survival (OS) rate and secondary endpoints were disease-free survival and pathologic response. Results: Of patients being treated between 2008 and 2014, 158 were entered to final analysis; they completed planned neoadjuvant treatment and retuned after surgery with pathology report. The mean age was 56 years and mean interval from radiotherapy to surgery was 9 weeks. Thirty percent achieved pathologic complete response. Two-year overall and disease-free survival rate was 87% and 80%, respectively. In multivariate analysis age, sex, local recurrence, clinical stage, and radiotherapy to surgery interval failed to predict OS. The pathologic response (complete vs. non-complete) and the absence of distant metastasis were independent predictors of OS. Conclusions: The rate of pathologic response and survival in our series was comparable to other big randomized studies in the world and even better than previous national reports. These findings emphasize the necessity of treating patients with locally advanced rectal cancer in high volume centers. [ABSTRACT FROM AUTHOR]

Background Clinical trials investigating the effects of addition of oxaliplatin to neoadjuvant radiochemotherapy in locally advanced rectal cancers (LARCs) have brought controversial results for pathologic complete response as an endpoint. This randomized clinical trial investigated downstaging as a short-term surrogate for progression-free survival (PFS). Methods Patients with magnetic resonance imaging (MRI) defined T3, T4 or N+ histologically proven adenocarcinoma of rectum within 15 cm from anal verge were randomly assigned to receive 50-50.4 Gy external beam radiation in 25-28 fractions and concurrent capecitabine 825 mg/m2 twice daily 5 days a week with or without oxaliplatin 60 mg/m2 weekly as neoadjuvant radiochemotherapy (Capox and Cap group, respectively). T downstage was defined as at least one stage regression in pathologic report after surgery comparing to MRI image before the preoperative treatment. Adverse effects of treatment were recorded on a weekly basis according to National Cancer Institute Common Toxicity Criteria, version 4. Results Sixty-three patients were randomly assigned to Cap ( n = 31) and Capox ( n = 32) groups. There was no grade 4 toxicity. The only grade 3 toxicity that occurred more in Capox group was diarrhea (22% vs 0%; P = 0.006). Histopathologic stage of 52 patients (27 patients in Cap and 25 patients in Capox groups) was compared to their preoperative stage defined by MRI. There was a greater rate of T downstage in Capox group (59% vs 42%; P = 0.037). Eleven patients in Capox group (34%) achieved pathologic complete response, comparing to four in Cap group (13%); P = 0.072. Conclusion The addition of oxalipatin to neoadjuvant radiochemotherapy in LARC led to higher rate of tumor downstaging. Longer follow-up is needed to evaluate PFS. [ABSTRACT FROM AUTHOR]