scholarly journals What we learn from randomized trials in rectal cancer and what we can trust

2014 ◽  
Vol 61 (2) ◽  
pp. 9-16
Author(s):  
Vincenzo Valentini ◽  
Francesco Cellini
Keyword(s):  
Rectal Cancer ◽  
Randomized Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Integrated Treatment ◽  
Treatment Schedule ◽  
Optimal Outcome ◽  
Progressive Development ◽  
Rectal Cancers

Results of the management of rectal cancer have enormously improved over the last almost forty years, by the progressive development of new integrated treatment options. nevertheless an optimization of the results is needed to raise the still sub-optimal outcome in terms of survival. several national and international guidelines address the best treatment choice overall evaluating the evidence basis available from literature. Still a certain degree of disagreement is present, particularly about the preferable preoperative rt treatment schedule. randomized trials represent the main landmark and most important tool for the scientific scenario: defining a potentially established standard of care, or suggesting the more promising approach to focus the re- search into, thus orienting the efforts of clinicians and researchers. This manuscript will mainly focus on the evidences derived from randomized clinical trial describing the main issues about the multimodal integrated treatment for rectal cancers. It will focus on both locally advanced (LA)/primary unresectable (UR), and resectable rectal cancers; some non-randomized trials of relevant the dissertation will also be mentioned.

scholarly journals A Non-Operative Approach to Rectal Cancer after Chemo-Radiotherapy:

2019 ◽  
Vol 12 (1) ◽  
pp. 17-19
Author(s):  
Abeer Arian
Keyword(s):  
Rectal Cancer ◽  
Watchful Waiting ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Operative Approach ◽  
Pathological Complete Remission ◽  
Care Approach ◽  
Rectal Cancers

Introduction. Chemotherapy administered concurrently withradiotherapy for locally-advanced rectal cancer prior to surgeryis a standard of care approach. A fraction of patients after chemoradiotherapyachieve pathological complete remission. Our aim wasto evaluate patients treated only with a non-operative approach ofonly chemo-radiotherapy followed by observation at a communitycancer center.Methods. Medical charts of the patients who were treated for locallyadvanced rectal cancer and treated with chemo-radiation therapyalone from January 1, 2000 through May 1, 2017 at a Midwesterncancer center were reviewed. The clinical course of the patients wasfollowed from the time of the cancer diagnosis through their last availableclinical record.Results. A series of three cases were reviewed with locally-advanceddistal rectal cancers treated with a non-operative approach.Conclusions. Watchful waiting for patients with locally advanceddistal rectal cancer who have complete clinical response with neoadjuvantchemotherapy and radiation might be an effective treatmentstrategy. Kans J Med 2019;12(1):17-19.

scholarly journals Prognostic Significance of EMVI in Rectal Cancer in a Tertiary Cancer Hospital in India

2021 ◽  
Author(s):  
Sayali Y. Pangarkar ◽  
Akshay D. Baheti ◽  
Kunal A. Mistry ◽  
Amit J. Choudhari ◽  
Vasundhara R. Patil ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Distant Metastasis ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Signet Ring Cell ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Signet Ring ◽  
Rectal Cancers ◽  
Ring Cell

Abstract Background Presence of extramural venous invasion (EMVI) is a poor prognostic factor for rectal cancer as per literature. However, India-specific data are lacking. Aim The aim of the study is to determine the prognostic significance of EMVI in locally advanced rectal cancer on baseline MRI. Materials and Methods We retrospectively reviewed 117 MRIs of operable non-metastatic locally advanced rectal cancers in a tertiary cancer institute. Three dedicated oncoradiologists determined presence or absence of EMVI, and its length and thickness, in consensus. These patients were treated as per standard institutional protocols and followed up for a median period of 37 months (range: 2–71 months). Kaplan-Meier curves (95% CI) were used to determine disease-free survival (DFS), distant-metastases free survival (DMFS), and overall survival (OS). Univariate analysis was performed by comparing groups with log-rank test. Results EMVI positive cases were 34/114 (29%). More EMVI-positive cases developed distant metastasis compared with EMVI-negative cases (14/34–41% vs. 22/83–26%). The difference, however, was not statistically significant (p = 0.146). After excluding signet-ring cell cancers (n = 14), EMVI showed significant correlation with DMFS (p = 0.046), but not with DFS or OS. The median thickness and length of EMVI was 6 and 14 mm, respectively in patients who developed distant metastasis, as compared with 5 and 11 mm in those who did not, although this difference was not statistically significant. Conclusion EMVI is a predictor of distant metastasis in locally advanced non-metastatic, non-signet ring cell rectal cancers. EMVI can be considered another high-risk feature to predict distant metastasis.

Neoadjuvant Chemotherapy to Radiation and Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Cervix: A Review of the Recent Literature

1998 ◽  
Vol 84 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Alessandro Colombo ◽  
Fabio Landoni ◽  
Andrea Maneo ◽  
Gerardo Zanetta ◽  
Simonetta Nava ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Local Control ◽  
Randomized Trials ◽  
Recent Literature ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Integrated Treatment ◽  
Concurrent Chemoradiation ◽  
Late Morbidity

Radiotherapy is the standard treatment for locally advanced cervical cancer; nevertheless it fails to control disease progression within the irradiation fields in more than 40% of cases, particularly in patients with bulky tumor. Distant metastases are not infrequent in more advanced cases. Chemotherapy has been integrated with radiotherapy to improve local control and treat distant subclinical metastases. Schedules of combined treatment more frequently represented by neoadjuvant chemotherapy followed by radiation (NACT) and by concomitant chemotherapy and radiation (CT-RT). A review of the recent literature is presented. The role of NACT is controversial: high response rates are reported but doubtful advantages in terms of survival or local control have been shown. In randomized trials, hydroxyurea concomitant to radiation improves local control and survival, particularly in stage IIIB and IVA. Several randomized trials of concurrent chemoradiation with 5FU, cisplatin and mitomycin C are underway, but few have been published: no significative differences are reported in term of local control or survival. Acute toxicity is higher than in radiation alone, but usually manageable. For the analysis of late morbidity a longer follow-up is required. Large randomized trials of adequate radiotherapy versus concomitant chemoradiation are necessary to refine our understanding of the benefits of this integrated treatment.

Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?

2018 ◽  
pp. 280-291 ◽  
Author(s):  
Elizabeth Cartwright ◽  
Florence K. Keane ◽  
Peter C. Enzinger ◽  
Theodore Hong ◽  
Ian Chau
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Global Consensus ◽  
Esophagogastric Cancer ◽  
Genetic Features ◽  
Related Mortality ◽  
Optimal Treatment Strategy

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

scholarly journals Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Alessandro Del Gobbo ◽  
Stefano Ferrero
Keyword(s):  
Rectal Cancer ◽  
State Of The Art ◽  
Tumor Regression ◽  
Dihydropyrimidine Dehydrogenase ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Response To Therapy ◽  
Tumor Regression Grade ◽  
Immunohistochemical Markers ◽  
Rectal Cancers

We explain the state of the art of the immunohistochemical markers of response in rectal cancers treated with neoadjuvant medical therapies and its implication with prognosis. Neoadjuvant chemoradiotherapy is widely used to improve the outcome of patients with locally advanced rectal cancer, and the evaluation of the effects of medical therapy is to date based on histomorphological examination by applying four grading systems of response to therapy (tumor regression grade (TRG)). The need to identify immunohistochemical markers that could ensure a better assessment of response and possibly provide additional prognostic information has emerged. We identified p53, p27kip1, Ki67, matrix metalloprotease-9, survivin, Ki67 proliferative index, CD133, COX2, CD44v6, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as the most common markers studied in literature to date, and we explained their prognostic potential and their implications in the evaluation of the response to preoperative therapies in rectal cancers.

Comparative quality of life in patients randomized contemporaneously to docetaxel or abiraterone in the STAMPEDE trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 14-14 ◽  
Author(s):  
Hannah L. Rush ◽  
Adrian David Cook ◽  
Christopher D. Brawley ◽  
Laura Murphy ◽  
Archie Macnair ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Repeated Measures ◽  
Treatment Options ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Clinical Parameter ◽  
Cross Sectional ◽  
Multi Stage ◽  
Eortc Qlq

14 Background: Docetaxel (DOC) and abiraterone (ABI) both improve overall survival (OS) in men with locally advanced or metastatic hormone-sensitive prostate cancer (HSPC) but no head to head trials compare the 2 agents. STAMPEDE, a multi-arm multi-stage platform trial, recruited patients (pts) to treatments including DOC or ABI between Nov-11 and Mar-13. There was no evidence OS differed between DOC or ABI, thus quality of life (QOL) may increasingly inform treatment options. Methods: QOL scores were analysed in pts contemporaneously randomised to receive DOC or ABI, in addition to standard of care treatment. Self-assessment QOL questionnaires EORTC QLQ C30 and PR25 were completed during treatment and follow-up. These analyses focus on average global QOL over the first 2 years after randomisation, using repeated measures analysis, plus cross-sectional analyses at 3, 6, 12 and 24 months. A score difference of ≥4 points was pre-defined as clinically meaningful. Results: 173 men randomised to DOC and 342 men randomised to ABI participated in the QOL sub-study and contributed to this analysis. Baseline characteristics and proportion of missing data were similar between groups. Baseline global QOL scores were similar (mean (sd): DOC 77.8 (20) and ABI 78.0 (19.3)). Average global QOL over 2 years was higher in pts randomised to ABI than DOC, although the difference was statistically significant it did not meet the pre-defined clinical parameter (+3.9, 95%CI 0.6 to 7.1, p=0.021). Cross-sectional analyses showed clinically meaningful superior QOL in the ABI group at 3 and 6 months (+6.6, 95%CI 2.6 to 10.7, p=0.001; +8.0, 95%CI 3.6 to 12.3, p<0.001), but not at 1 or 2 years (+1.3, 95%CI -3.0 to 5.6, p=0.545; +4.5, 95%CI -0.25 to 9.2, p=0.063). An exploratory analysis indicated average QOL for pts with metastatic disease (n=207) was better in the ABI group (+4.44, 95%CI 0.2 to 8.6, p=0.036). Conclusion: Global QOL was significantly higher in the first 2 years of treatment for the ABI group compared to the DOC group, though did not meet the pre-defined clinically meaningful threshold. The majority of difference was seen in the first year of treatment. This should be considered when discussing treatment options with pts. Clinical trial information: NCT00268476.

scholarly journals A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Séan M. O’Cathail ◽  
Steven Davis ◽  
Jane Holmes ◽  
Richard Brown ◽  
Kerry Fisher ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Biological Effects ◽  
Phase 1 ◽  
Locally Advanced ◽  
Statistical Design ◽  
Optimal Dose ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Treatment Schedule ◽  
New Paradigm

Abstract Background Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. Methods Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for ‘proof-of-concept’ and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. Discussion Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. Trial registration ClinicalTrial.gov, NCT03916510. Registered 16th April 2019.

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