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The epidermal growth factor receptor (EGFR) inhibitor cetuximab has been successfully combined with radical radiotherapy in head and neck cancer. In colorectal cancer, increased response rates are achieved by cetuximab and panitumumab within standard chemotherapy schedules, but not in chemoradiation regimens. This review examines the clinical evidence and potential mechanisms for an interaction when EGFR inhibitors are added to fluoropyrimidine-based chemoradiation in rectal adenocarcinoma. Methods. This review was compiled by searching PubMed and Medline for English language articles published until 2009 with established search strategies, supplemented by hand searching of abstracts from the proceedings of relevant international meetings. The primary outcome measure was pathological complete response (pCR). Results. Only 13 publications and three presentations in abstract of 13 phase I/II trials of preoperative chemoradiation with cetuximab in rectal cancer were identified. A total of 316 patients were identified who received cetuximab in combination with radiotherapy and 5-fluorouracil or capecitabine preoperatively. One hundred and thirty eight of these patients received either additional irinotecan or oxaliplatin. One study with panitumumab with safety but no efficacy results was identified, and two studies with gefinitib. The pCR rate ranged from 0-20%. The overall pooled pCR for cetuximab based chemoradiation was 9.1% (29/316). The rate of G3/G4 gastrointestinal toxicity, in terms of diarrhoea, varied from 5-30%, with an overall pooled rate of 47/313 (15%). Discussion. Potential reasons for the disappointing results of EGFR inhibition with fluoropyrimidine-based preoperative chemoradiation include a less critical role of repopulation in rectal adenocarcinoma using a non-curative radiation dose; or antagonistic effects on 5FU-based chemoradiation and oxaliplatin, if some cells arrest in G1 or G2-M and fail to pass through S phase. Conclusion. Cetuximab combined with fluoropyrimidine-based chemoradiation is not currently recommended. A better understanding of the mechanisms involved in combinations of chemotherapy and radiotherapy might allow more effective future scheduling of biological and chemical agents in combination with radiation. [ABSTRACT FROM AUTHOR]

The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1α (HIF-1α) and HIF-2α protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n=90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1α and HIF-2α expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1α and HIF-2α, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (P<0.001) and associated with poor survival (hazard ratio (HR)=8.7, P<0.005) and decreased disease-free survival (HR=4.7, P<0.005). hypoxia-inducible factor-1α and -2α were expressed in >50% of rectal cancers (HIF-1α, 54%, 48/90; HIF-2α, 64%, 58/90). HIF-1α positivity was associated with both TNM stage (P<0.05) and vascular invasion (P<0.005). In contrast, no associations were shown between HIF-2α expression and any pathological features, and HIF-1α positivity had no effect on outcome. The study showed an independent association between HIF-1α expression and advanced TNM stage with poor outcome. Our results indicate that HIF-1α, but not HIF-2α, might be used as a marker of prognosis, in addition to methods currently used, to enhance patient management.British Journal of Cancer (2009) 100, 1666–1673. doi:10.1038/sj.bjc.6605026 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Purpose Since 1943 [ 1 ], only 45 patients of squamous cancer of the rectum have been reported in the published reports and the largest series to date consists of 12 patients. Reports suggest that the primary treatment is surgical resection but, in the light of nonsurgical advances in the treatment of anal squamous cell carcinoma (SCC), we present a review of the literature and report six patients treated by chemoradiation therapy (CRT). Method A literature search was undertaken using the keywords squamous cell, epidermoid, basaloid and cloacagenic and cancer of rectum and colon to provide evidence for this discussion from studies of surgery, radiation therapy and CRT in rectal SCC. A prospective database of the Mount Vernon Cancer Centre, UK was searched from 1995 to 2005 for patients diagnosed with pure SCC of the rectum. Results Six patients with histologically confirmed primary SCC of the rectum were treated with primary combination chemo-radiotherapy according to protocols used for SCC of the anal canal over a 15-year period. Surgery was avoided in four, and they remain disease-free on follow-up. Conclusions Primary CRT, as currently utilized in anal cancer, can be extended to primary SCC of the rectum. [ABSTRACT FROM AUTHOR]

Blanket use of radiotherapy unwarranted [ABSTRACT FROM AUTHOR]

The article presents a study on delaying surgery after neoadjuvant chemoradiotherapy for rectal cancer. The study aims to analyze whether the interval between neoadjuvant chemoradiotherapy and surgery for the cancer impact the postoperative morbidity or prognosis. It is concluded that delaying surgery after chemoradiotherapy may lessen postoperative morbidity without compromising prognosis.

Purpose: 5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients. Methods and Materials: Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m2) on Day 1 and capecitabine on each RT treatment day in two divided doses (825 mg/m2 b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity. Results: Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred. Conclusions: Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: To throw light on some of the issues in the choice of therapy for patients with metastatic colorectal cancer (mCRC) and to provide consensus recommendations on which combination(s) and sequence(s) of systemic therapy to be used in different treatment situations. MATERIAL AND METHODS: An expert panel comprising clinicians from Austria, Belgium, the Czech Republic, Germany, Hungary, Italy, Romania, Slovakia, Slovenia, Spain and the UK with expertise in medical oncology, clinical oncology, surgery and dermatology, and specialist knowledge of the treatment of patients with CRC was convened by the Central European Cooperative Oncology Group (CECOG) in Vienna in 2007. Members were then asked to agree on a consensus statement following a period of discussion at the end of a series of presentations. RESULTS AND CONCLUSIONS: The consensus recommendations for the state-of-the-art treatment of colon cancer arrived at by an "expert panel" of clinicians were that: oral 5-fluorouracil (5-FU) prodrugs or protracted intravenous infusion of the antimetabolite are preferable to bolus administration; all active drugs (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, cetuximab) should be used during strategic patient management; after neoadjuvant treatment and consultation of an interdisciplinary team, surgery should be considered for metastatic disease wherever possible and "fit" elderly patients should not be denied the same treatment as younger patients. [ABSTRACT FROM AUTHOR]

A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of “waiting to see” and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery. In total, 218 Phase I/II or retrospective studies and 28 Phase III trials of preoperative radiotherapy or chemoradiation were identified: 96 percent of trials documented the pathologic complete response, but only 38 trials presented data on the achievement of a complete clinical response/partial clinical response. Only five studies were found in which patients with clinically staged T2/T3 tumors were treated with radiotherapy/chemoradiation and did not routinely proceed to surgery and also reported on the long-term outcome of a “wait and see” policy. It remains uncertain whether the degree of response to chemoradiation in terms of complete clinical response or pathologic complete response is a useful clinical end point. Studies that include T3 rectal cancer are associated with high local recurrence rates after nonsurgical treatment. Few studies report long-term outcome after achievement of a complete clinical response. The end point of complete clinical response is inconsistently defined and seems insufficiently robust with only partial concordance with pathologic complete response. The rationale of a “wait and see” policy when complete clinical response status is achieved relies on retrospective observations, which are currently insufficient to support this policy except in patients who are recognized to be unfit for or refuse radical surgery. [ABSTRACT FROM AUTHOR]

Total mesorectal excision and preoperative radiation with or without chemotherapy has led to a reduction in local recurrence rates in patients with rectal cancer. This article examines the effect such treatment has on the rate of sphincter preservation in patients with rectal cancers close to the anal sphincter mechanism and looks at the evidence for changing clinical practice. [ABSTRACT FROM AUTHOR]

Background: The Buschke-Löwenstein tumour (BIT) or giant condytoma acuminata is a rare disease which affects the anogenital region. Although histologically benign, it behaves in a malignant fashion, infiltrating the surrounding tissues. The morbidity and mortality from this tumour is high, as is the risk of recurrence following treatment. It lies on the continuum between the benign condylomata acuminata and squamous cell carcinoma. The human papillomavirus is implicated in its aetiology. Treatment is controversial, with topical chemotherapy, radiotherapy, immunotherapy and radical surgery all having been employed. Chemoradiation remains the mainstay of treatment for anal cancers but has not been routinely employed in the management of the BIT without squamous cell carcinoma transformation.

Objective The presence of microscopic tumour cells within 1 mm of the circumferential surgical resection margin (CRM) is the endpoint most strongly associated with local recurrence in rectal cancer and doubles the risk of developing distant metastases. Reporting on the CRM can monitor surgical quality assurance and over the past two decades has driven advances in surgical technique with the increasing use of total mesorectal excision. The aim of this review was to use the evidence from both phase II and phase III randomized trials of preoperative radiotherapy and chemoradiation in rectal cancer, to assess how often CRM involvement is currently documented and examine its utility as an early predictor of both disease-free and overall survival. Method A literature search identified both randomized and nonrandomized trials of preoperative radiation therapy and chemoradiation therapy in rectal cancer since 1993. The aim was to find those studies, which documented the distance from the periphery of the tumour and the CRM. Small trials treating < 20 patients were excluded. Results One hundred and eighty-seven phase II and 28 phase III trials of preoperative radiotherapy or chemoradiation were identified. Most trials documented the degree of response but only 10 of 187 phase II/retrospective studies and four of 28 phase III trials presented data on the achievement of a negative CRM. Few defined this early pathological endpoint prospectively with accurate measurements. However, the majority of studies did use the definition of ≤ 1 mm as an involved CRM. Discussion Pathological parameters have been used as early endpoints to compare studies of preoperative radiotherapy or chemoradiation. It remains uncertain whether the degree of response to chemoradiation (e.g. complete pathological response, downsizing the primary tumour, sterilizing the regional nodes, tumour regression grades or residual cell density) or the achievement of a curative resection (uninvolved CRM) is the best early clinical endpoint. Retrospective studies in rectal cancer have confirmed a strong association between the presence of microscopic tumour cells within 1 mm of the CRM and increased risks of both local recurrence and distant metastases. However, as yet this early pathological endpoint lacks structured measurement and analysis techniques to control for intra- and inter-observer variation and has not been validated as a potential surrogate for local control and survival. Recommendations are made as to the most appropriate information, which should be documented in future trials. Conclusion The CRM status predicts outcome after surgery alone, preoperative radiotherapy and preoperative chemoradiation. Yet CRM status and its measurement has been poorly documented in the literature, and rarely as a prospective measure of outcome. The CRM should be measured and documented in all cases, using the definition of ≤ 1 mm to denote an involved CRM. This definition should also be incorporated into future rectal cancer studies with the use of a standardized proforma. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the use of magnetic resonance imaging (MRI) for non-invasive measurement of rectal cancer angiogenesis and hypoxia. Methods: Fifteen patients with rectal adenocarcinoma underwent preoperative dynamic contrast-enhanced (DCE) and blood oxygenation level-dependent (BOLD) MRI. Microvessel density (CD31 level), and expression of vascular endothelial growth factor (VEGF) and carbonic anhydrase (CA) 9 were measured immunohistochemically in histological tumour sections from 12 patients. Serum VEGF levels were also measured in 14 patients. Correlations between quantitative imaging indices and immunohistochemical variables were examined. Results: There was good correlation between circulating VEGF and CD31 expression (rS = 0.88, P < 0.001). CD31 expression did not correlate with any dynamic MRI parameter, except transfer constant, with which it correlated inversely (rS = -0.65, P = 0.022). Tissue and circulating VEGF levels did not correlate, and neither correlated with any tumour DCE MRI parameter. No relationship was seen between BOLD MRI and CA-9 expression. Conclusion: The negative correlation between transfer constant (reflecting tumour blood flow and microvessel permeability) with CD31 expression is paradoxical. DCE MRI methods for assessing tissue vascularity correlate poorly with histological markers of angiogenesis and hypoxia, suggesting that DCE MRI does not simply reflect static histological vascular properties in patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Delays in tissue fixation following tumour vascular clamping and extirpation may adversely affect subsequent protein and mRNA analysis. This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase. Vascular occlusion of human tumour xenografts by D-shaped metal clamps permitted defined periods of tumour ischaemia. Alterations in protein expression were measured by immunohistochemistry and spectral imaging, and changes in mRNA were measured by reverse transcriptase-polymerase chain reaction. Thymidylate synthase expression decreased following vascular occlusion, and this correlated with cyclin A expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen. There were significant changes in the expression of several hypoxic markers, with carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels were also noted to change following tumour clamping. In this xenograft model, surgically induced tumour ischaemia considerably altered the gene expression profiles of several prognostic and hypoxic markers, suggesting that the degree of tumour ischaemia should be minimised prior to tissue fixation. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined whether a pathological complete response in the primary tumor following pre-operative chemoradiation (CRT) for T3-T4 rectal cancer can predict a response within the perirectal lymph nodes, a low risk of local recurrence and the appropriateness of local excision. The characteristics, treatment details and outcome of patients undergoing preoperative CRT for rectal carcinomas considered unresectable between November 1993 and August 2003 were recorded. Patients were reassessed after completing CRT. Planned surgical resection was carried out after treatment. 68 patients did not proceed to surgery due to preoperative death, inoperable disease and patient refusal or concurrent medical problems.

Radiation therapy is well established in the treatment of early and locally advanced rectal cancer, where it has been used in both the pre-operative and postoperative settings. Pre-operatively, radiation therapy has been shown in a series of studies culminating in the Dutch total mesorectal excision (TME) study to significantly reduce the rate of local recurrence at 2 years. However, the overall rate of survival was not improved in this study because radiotherapy failed to reduce the incidence of distant metastases. Chemotherapy, however, may reduce distant metastatic spread, as well as increasing the rate of R0 resectability and sphincter-saving surgery when used in combination with radiotherapy in the neoadjuvant setting. Oxaliplatin is a prime candidate for radiochemotherapy in rectal cancer because it frequently has large and rapid cytoreductive effects in colorectal malignancies and has been shown in vitro and preclinical models to be radiosensitizing. In an Italian phase I/II study, weekly oxaliplatin combined with standard infusional 5-FU and pre-operative radiotherapy has shown low toxicity and promising antitumour activity. These encouraging results are now being followed up in a more extensive trials programme. A randomized trial comparing this regimen with standard infusional FUra and radiotherapy (STAR, Studio nazonaleTerapia neoAdiuvante Retto [National Study on Neoadjuvant Treatment of Rectal cancer]) is being launched in Italy. A new phase II study, CORE (Capecitabine, Oxaliplatin, Radiotherapy and Excision), is now in development in Europe and will use a similar weekly treatment regimen with an oral fluropyrimidine in place of infusional FUra, and a number of further oxaliplatin-based radiochemotherapy studies in rectal cancer are planned or in progress. In summary, radiochemotherapy appears to have the potential to significantly improve clinical outcomes in rectal cancer, and oxaliplatin-based treatment is proving central to its ongoing development. [ABSTRACT FROM AUTHOR]

Synchronous chemoradiation (SCRT) is playing an increasing role in the primary and multimodality management of cancer in many disease sites. Current schedules have been in the main empirically derived, and the addition of chemotherapy has in some cases led to a compromise in the total dose or scheduling of radiotherapy. Non-randomised phase II studies abound, but there are few well designed phase III randomised studies with comprehensive acute toxicity data and mature follow-up. In many sites long-term survival is unusual. So severe morbidity and long term functional outcome is poorly documented. It is therefore difficult to assess the real benefit of SCRT. This review uses the endpoints of local control and overall survival from randomised trials in small and non-small cell lung cancer, head and neck cancer, oesophageal cancer, rectal and anal cancer. We explore the evidence for total dose; fractionation; fraction size; the effects of a gap in treatment; and scheduling of radiation in SCRT.Conclusions: An optimal schedule of SCRT has not yet been derived. The enhanced acute toxicity and persistent high risk of local failure in many disease settings with current SCRT schedules demand that more effective and less toxic treatment strategies must be identified in the future. These schedules should be tested in randomised trials with the emphasis on meticulous reporting of acute toxicity endpoint and documenting the field sizes or proportions of critical organs within the high dose area if we are to derive the optimal therapeutic ratio. [Copyright &y& Elsevier]

Summary Background Oesophageal cancer carries a poor prognosis. The 5-year survival rate following resection ranges from 10 to 35 per cent. Recent evidence suggests that the addition of non-surgical treatments to surgery may improve resection rates, reduce the risk of recurrence and improve survival. This review examines the role of preoperative chemoradiotherapy (CRT) in oesophageal cancer. Methods A Medline-based literature review (1980–2000) was performed using the key words ‘neoadjuvant or preoperative’ and ‘chemoradiotherapy or radiochemotherapy’. Additional literature was obtained from original papers and published meeting abstracts. Results Forty-six non-randomized and six randomized trials of preoperative CRT were found. Resection rates, pathological complete response (pCR), treatment-related mortality rates and relapse patterns are documented. Improved 5-year survival rates approaching 60 per cent may be achieved following pCR. Three of the six randomized trials show a benefit in either overall survival or disease-free survival compared with surgery alone. Treatment-related toxicity can be significant. Conclusion Preoperative CRT may improve survival. Emerging evidence suggests that CRT alone can achieve similar survival rates to surgery alone. New imaging modalities may help to select which patients require surgery. Larger randomized trials of preoperative CRT or chemotherapy are needed to define optimal regimens and produce higher pCR rates with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Background: The improved overall survival (OS) after short course preoperative radiotherapy (SCPRT) using 5 × 5 Gy reported in the early rectal cancer trials could not be replicated in subsequent phase III trials. This original survival advantage is attributed to poor quality of surgery and the large differential in local recurrence rates, with and without SCPRT. Immuno-modulation during and after SCPRT and its clinical implications have been poorly investigated. We propose an alternative explanation for this survival benefit in terms of immunological mechanisms induced by SCPRT and the timing of surgery, which may validate the concept of consolidation chemotherapy.Material and Methods: We reviewed randomized controlled trials (RCTs) and studies of SCPRT from 1985 to 2019. We aimed to examine the precise timing of surgery in days following SCPRT and identify evidence for immune modulation, neo-antigens and memory cell induction by radiation.Results: Considerable variability is reported in randomised trials for median overall treatment time (OTT) from start of SCPRT to surgery (8-14 days). Only three early trials showed a benefit in terms of OS from SCPRT, although the level of benefit in preventing local recurrence was consistent across all trials. Different patterns of immune effects are observed within days after SCPRT depending on the OTT, but human leukocyte antigen (HLA)-1 expression was not upregulated.Conclusions: SCPRT has a substantial immune-stimulatory potential. The importance of the timing of surgery after SCPRT may have been underestimated. An optimal interval for surgery after 5 × 5 Gy may lead to better outcomes, which is possibly exploited in total neoadjuvant therapy schedules using consolidation chemotherapy. Individual patient meta-analyses from appropriate SCPRT trials examining outcomes for each day and prospective trials are needed to clarify the validity of this hypothesis. The interaction of SCPRT with tumour adaptive immunology, in particular the kinetics and timing, should be examined further. [ABSTRACT FROM AUTHOR]

At the Royal Free Hospital (London), we have conventionally favoured LCCR followed by radical surgery after a delay of 8-10 weeks in patients with LARC. It is also likely that the chances of significant treatment interruption if the patient were to test positive for COVID-19 would be reduced with SCRT, compared with LCCR. 5 Erlandsson J, Pettersson D, Glimelius B, Holm T, Martling A. Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy. [Extracted from the article]

Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients' data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6-78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6-194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution-particularly in females with involvement of the vagina or the vaginal septum. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the defunctioning stomas in patients with locally advanced rectal cancer prior to preoperative chemoradiotherapy.

The article focuses on the clinical practice guidelines of the European Society for Medical Oncology (ESMO) for the diagnosis, treatment, and follow-up treatment of patients with an epidermoid anal cancer. It mentions that the diagnosis of epidermoid anal cancer includes documentation of predisposing factors and history of symptoms, and protoscopy. It states various recommendations for the treatment of anal cancer which include local excision, radiobiologically, and modality chemoradiation.

In this article, the author discusses the colorectal cancer research along with its treatment. Topics discussed include the use of molecular targeted agents for treatment of cancer, the use of triple combinations of chemotherapy comprising oxaliplatin, irinotecan and 5-fluorouracil (5-FU); and suggests to view their website located at www.currentmedicalliterature.com.

The article presents clinical recommendations for diagnosis, treatment and follow-up of anal cancer from the European Society for Medical Oncology (ESMO). The disease is rare and its annual incidence is roughly 1 in 100,000 and is higher in women than in men. Following the removal of anal tags, early cancers are sometimes diagnosed accidentally. Information is also presented on staging and risk assessment, radiotherapy technique and treatment fields.

An introduction to journal is presented in which the editor discusses colorectal cancer research for scientists and clinicians who were interested in colorectal cancer field.

In this article, the author discussess about colorectal cancer. Topics discussed include treatment of the same using chemotherapy, radiotherapy and surgical technique; treatment outcomes of colorectal cancer patients; and medical technological developments made in the field of genetics and molecular biology.

Aims This single-centre retrospective study evaluated combination external beam radiotherapy and high dose rate brachytherapy for patients in whom radical treatment was appropriate but comorbidity or frailty excluded this as an option. Materials and methods In total, 59 patients were selected for a combined approach and treated between October 2000 and October 2011; 68% were male. The median age was 77 years (range 53–88 years); 66% had adenocarcinoma, 31% squamous cell carcinoma. Tumour stage: I: 20%, II: 43%, III: 32% and IV: 3%. External beam radiotherapy doses of either 27 Gy/six fractions or 30 Gy/10 fractions were delivered, followed by high dose rate brachytherapy at doses of either 10 or 15 Gy utilising an iridium 192 source at 1 cm. Results The median overall survival of all treated patients was 12.3 months; 1, 2 and 3 year survival rates were 51, 19 and 7%, respectively. Patients with stage I disease had a median survival of 16 months compared with 10 months for patients with stage III disease ( P = 0.036). The pretreatment dysphagia score was associated with survival ( P = 0.021). Conclusions This study shows the value of a purely radiation-based approach in a selected population. Treatment is deliverable with excellent compliance and the median survival compares favourably with unselected patients treated palliatively in our institution. [ABSTRACT FROM AUTHOR]

Background: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. Methods: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1–5 and 8–12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1–14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. Results: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0–23.7) with TT-B and 17.7 months (95% CI: 12.6–19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55–1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. Conclusions: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. Clinical trial information: NCT02743221 (clinicaltrials.gov) [ABSTRACT FROM AUTHOR]

Chemotherapy dosing is traditionally based on body surface area calculations; however, these calculations ignore separate tissue compartments, such as the lean body mass (LBM), which is considered a big pool of drug distribution. In our era, colorectal cancer patients undergo a plethora of computed tomography scans as part of their diagnosis, staging and monitoring, which could easily be used for body composition analysis and LBM calculation, allowing for personalised chemotherapy dosing. This systematic review aims to evaluate the effect of muscle mass on dose-limiting toxicity (DLT), among different chemotherapy regimens used in colorectal cancer patients. This review was carried out according to the PRISMA guidelines. MEDLINE and EMBASE databases were searched from 1946 to August 2019. The primary search terms were 'sarcopenia', 'myopenia', 'chemotherapy toxicity', 'chemotherapy dosing', 'dose limiting toxicity', 'colorectal cancer', 'primary colorectal cancer' and 'metastatic colorectal cancer'. Outcomes of interest were – DLT and chemotoxicity related to body composition, and chemotherapy dosing on LBM. In total, 363 studies were identified, with 10 studies fulfilling the selection criteria. Seven studies were retrospective and three were prospective. Most studies used the same body composition analysis software but the chemotherapy regimens used varied. Due to marked study heterogeneity, quantitative data synthesis was not possible. Two studies described a toxicity cut-off value for 5-fluorouracil and one for oxaliplatin based on LBM. The rest of the studies showed an association between different body composition metrics and DLTs. Prospective studies are required with a larger colorectal cancer cohort, longitudinal monitoring of body composition changes during treatment, similar body composition analysis techniques, agreed cut-off values and standardised chemotherapy regimens. Incorporation of body composition analysis in the clinical setting will allow early identification of sarcopenic patients, personalised dosing based on their LBM and early optimisation of these patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]