Use Of Neoadjuvant Radiotherapy Research Articles

Neoadjuvant Chemoimmunotherapy for NSCLC

To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%. To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials. MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients. Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded. Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis. Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%). This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.

Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts

BackgroundIn the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. MethodsPatients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. ResultsUse of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). ConclusionPrimary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

Inequalities in the recovery of colorectal cancer services during the COVID-19 pandemic: a national population-based study.

Evidence is lacking on whether there were inequalities in the recovery of colorectal cancer (CRC) services within the English National Health Service (NHS) following the COVID-19 pandemic. The aim of this study was to evaluate recovery according to patient age and socioeconomic status. Using routinely collected data, CRC patients diagnosed and treated in the English NHS were identified for two timeframes: the 'initial pandemic period' (April-June 2020) and the 'pandemic period' (April 2020-March 2022). Poisson models evaluated changes in numbers of diagnoses, major resections, adjuvant chemotherapy and neoadjuvant radiotherapy use for each timeframe, relative to the equivalent pre-pandemic timeframe (April-June 2019 and April 2018-March 2020, respectively), stratified by age and socioeconomic status. Tumour stage at presentation was evaluated over time. Substantial deficits in diagnoses, major resections and adjuvant chemotherapy were identified in the initial pandemic period, whilst the use of neoadjuvant radiotherapy increased. Overall, these deficits recovered. Patients outside screening age, and in the most deprived group, had greater deficits in diagnoses and major resections. There was no evidence of stage migration by June 2021. CRC services showed recovery to baseline during the pandemic. However, evident inequalities must be addressed in ongoing recovery efforts. Long-term outcomes will fully establish the impact of the pandemic on CRC patients.

Trends and Variation in the Use of Radiotherapy in Non-metastatic Rectal Cancer: a 14-year Nationwide Overview from the Netherlands

AimsThis study describes nationwide primary radiotherapy utilisation trends for non-metastasised rectal cancer in the Netherlands between 2008 and 2021. In 2014, both colorectal cancer screening and a new guideline specifying prognostic risk groups for neoadjuvant treatment were implemented. Materials and methodsPatients with non-metastasised rectal cancer in 2008–2021 (n = 37 510) were selected from the Netherlands Cancer Registry and classified into prognostic risk groups. Treatment was studied over time and age. Multilevel logistic regression analyses were carried out to identify factors associated with (i) radiotherapy versus chemoradiotherapy use for intermediate rectal cancer and (ii) chemoradiotherapy without versus with surgery for locally advanced rectal cancer. ResultsFor early rectal cancer, the use of neoadjuvant radiotherapy decreased (15% to 5% between 2008 and 2021), whereas the use of endoscopic resections increased (8% in 2015, 17% in 2021). In intermediate-risk rectal cancer, neoadjuvant chemoradiotherapy (43% until 2011, 25% in 2015) shifted to radiotherapy (42% in 2008, 50% in 2015), the latter being most often applied in older patients. In locally advanced rectal cancer, the use of chemoradiotherapy without surgery increased (2–4% in 2008–2013, 17% in 2019–2021). Both neoadjuvant treatment in intermediate disease and omission of surgery following chemoradiotherapy in locally advanced disease varied with increasing age (odds ratio>75vs<50: 2.17, 95% confidence interval 1.54–3.06) and treatment region (Southwest and Northwest odds ratio 0.63, 95% confidence interval 0.42–0.93 and odds ratio 0.65, 95% confidence interval 0.44–0.95, respectively, compared with the North). ConclusionTreatment patterns in non-metastasised rectal cancer significantly changed over time. Effects of both the national screening programme and the new treatment guideline were apparent, as well as a paradigm shift towards organ preservation (watch-and-wait). Observed regional variations may indicate adoption differences regarding new treatment strategies.

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes

Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. The main outcomes were 4-year local recurrence and overall survival rates. Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

The Conditioning of Adjuvant Chemotherapy for Stage II and III Rectal Cancer Determined by Postoperative Pathological Characteristics in Romania.

The management of locally advanced rectal cancer (LARC) suffered changes thanks to the development of improved surgical procedures, radiation delivery, and chemotherapy. Although treatment options improved individually, the optimal order is still debated. Neoadjuvant chemo-radiotherapy followed by total mesorectal excision (TME) has been the "golden standard" for locally advanced rectal cancer. There is no common ground in international guidelines on the indications of adjuvant chemotherapy (ADJCHT), with differences between the American, European, and Japanese guidelines. This paper studies the preferences of Romanian oncologists in prescribing ADJCHT. We conducted a single-institution, retrospective study of all nonmetastatic, ECOG 0-1 LARC patients staged II-III who underwent TME and were admitted to the Oncology or Radiotherapy Department of Colțea Clinical Hospital, Bucharest between January 2017 and March 2021. A total of 186 patients were included in the study. A positive correlation was found between ADJCHT and each of the following: (y)pT > 2, (y)pN > 0, and the presence of perineural invasion (PNI+). A strong positive correlation was found between ADJCHT and the presence of at least one risk factor: (y)pT > 2, (y)pN > 0, PNI+, lymphovascular invasion, positive margins, or tumor grade > 1. Tumor downstaging decreased the risk of metastases in the first 2 years and was associated with the use of neoadjuvant radiotherapy, while adding neoadjuvant chemotherapy increased the chance of nodal downstaging. ADJCHT practice for LARC in Romania follows either NCCN or ESMO guidelines, at the discretion of the oncologist, due to the lack of national guideline.

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

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

Pelvic lymph node dissection alone versus adjuvant radiotherapy in node positive penile cancer: A systematic review.

Introduction:The management options for regional lymph nodes (LNs) in men with penile cancer include surveillance, surgery, and chemotherapy. The use of radiotherapy (RT) for nodal disease follows tradition and single-institution policies. We aimed to analyse the existing evidence regarding the management of penile cancer patients with suspected or known metastatic pelvic LNs using pelvic LN dissection (PLND) with RT versus PLND or RT alone.Methods:A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with no filters for language or time. The search was conducted in EMBASE, MEDLINE/PubMed, and Cochrane Library. Inclusion criteria were adult men with penile cancer and suspected metastatic pelvic LNs, undergoing PLND with or without RT or RT alone. Primary outcomes included disease-specific survival and locoregional recurrence. Secondary outcomes included overall survival and complications of therapy.Results:A total of 552 articles were identified. Only eight retrospective studies were eligible for inclusion (including 406 patients). All studies had a high risk of bias. None of the studies reported the use of neoadjuvant RT. Indications for PLND varied but were usually two or more clinically positive inguinal nodes with or without extracapsular extension. Adjuvant RT was mainly used in positive pelvic LNs or pN2/pN3 stages. The rate of locoregional recurrence following adjuvant RT was 70%. Complications of treatment were reported in two studies only.Conclusions:There is insufficient evidence to recommend the use of adjuvant RT following PLND in penile cancer patients. The quality of evidence is low due to the retrospective design and high risk of bias. Randomized clinical trials are required to assess the efficacy and safety of adjuvant RT and PLND.

Changes in rectal cancer treatment after the introduction of a national screening program; Increasing use of less invasive strategies within a national cohort

AimOrgan preserving treatment strategies and the introduction of a colorectal cancer-screening program have likely influenced the resection rates of rectal cancer. The aim of this study is to assess the influence of these developments on rectal cancer treatment and resection rates in the Netherlands. MethodsPatients diagnosed with non-metastatic rectal cancer between 2013 and 2018, were selected from the Netherlands Cancer Registry. The distribution of surgical and neo-adjuvant treatment and resection rates were analyzed and compared over time. ResultsBetween 2013 and 2018 22640 patients were diagnosed with non-metastatic rectal cancer. The incidence of early stage (cT1) disease increased from 141 (4%) in 2013 to 448 (12%) in 2018. The use of neoadjuvant radiotherapy and chemo-radiotherapy dropped from 39% to 21% and 34%–25%, respectively. A decrease in surgical resection rates (including TEM) was observed from 85% to 73%. The proportion of patients who underwent endoscopic resections increased from 3% to 10%. The decrease in surgical resection rates was larger in patients treated with neo-adjuvant chemo-radiotherapy. ConclusionAn increase in stage I disease is noted after the introduction of the screening program. Surgical resection rates for rectal cancer have fallen over time. Endoscopic resections due to more early-stage disease probably accounts for a large part of this decline. Furthermore, a watch and wait approach after neo-adjuvant chemo-radiotherapy may play an important role as well.

Neoadjuvant radiotherapy for locally advanced and high-risk breast cancer.

Neoadjuvant radiotherapy (NART) as part of a multi-modality approach for locally advanced breast cancer (LABC) requires further investigation. Importantly, this approach may allow for a single-staged surgical procedure, with mastectomy and immediate autologous reconstruction. Multiple other potential benefits of NART include improved pathological downstaging of breast disease, reduced overall treatment time, elimination of time period with breast tissue deficit and improved patient satisfaction. This is a retrospective multi-institutional review of patients with LABC and high-risk breast disease undergoing NART. Eligible patients sequentially underwent neoadjuvant chemotherapy (NACT) with or without HER2-targeted therapy, NART, followed by mastectomy with immediate autologous breast reconstruction (BR) 4- to 6 weeks post-completion of radiotherapy. Patient and tumour characteristics were analysed using descriptive statistics. Surgical complications were assessed using the Clavien-Dindo Classification (Ann Surg 2004; 240: 205). From 3/2013 to 9/2019, 153 patients were treated with NART. The median age was 47 years (IQR 42-52), with median body mass index of 27. Eighteen patients experienced Grade 3 acute surgical complications. This included 13 Grade 3B breast-site events and 9 Grade 3B donor-site events, where further surgical intervention was required for management of wound infection, wound dehiscence, flap or mastectomy skin necrosis, haematoma and internal mammary venous anastomotic thrombosis. No autologous flap loss was observed. Neoadjuvant radiotherapy facilitates a single-stage surgical procedure with mastectomy and immediate autologous BR, eliminating the delay to reconstructive surgery and thus shortening a woman's breast cancer journey. The findings of this review support the use of NART, with comparable rates of surgical complications to standard sequencing.

Neoadjuvant Short-Course Radiotherapy for Upper Third Rectal Tumors: Systematic Review and Individual Patient Data Metaanalysis of Randomized Controlled Trials.

There is no consensus on the use of neoadjuvant radiotherapy for tumors of the upper third of the rectum. Due to conflicting findings in high-quality trials and significant long-term side effects associated with neoadjuvant radiotherapy, the benefit of neoadjuvant radiotherapy for upper third rectal tumors is less certain than for lower two third rectal tumors. This metaanalysis compares oncological outcomes with neoadjuvant radiotherapy and surgery versus surgery alone for upper third rectal tumors. PubMed, Embase, and the Cochrane library databases were searched. Randomized controlled trials (RCT) comparing neoadjuvant radiotherapy and surgery versus surgery alone for resectable rectal cancer were included. Individual patient data were sought from the principal investigator of each eligible trial for comparative data on patients with upper third rectal tumors. The main outcomes measured were survival outcomes, oncological outcomes, postoperative morbidity, and late toxicity. Individual patient data from two RCTs examining outcomes in 758 patients were obtained. Published data from one further RCT containing comparable data on upper third rectal tumors were included in analysis of local recurrence. In patients with curative surgery, there was no significant reduction in local recurrence or significant improvement in overall survival or disease-free survival with neoadjuvant radiotherapy (LR RR: 0.38, 95% CI 0.14-1.04, p = 0.06) (OS RR: 1.10, 95% CI 0.98-1.24, p = 0.11) (DFS RR: 1.11, 95% CI 0.97-1.26, p = 0.13). The benefit of neoadjuvant radiotherapy for upper third rectal tumors is not certain, and surgery alone for patients with potentially curative disease at preoperative staging may be sufficient.

A systematic review of neo-adjuvant radiotherapy in the treatment of breast cancer.

IntroductionThe use of neo-adjuvant radiotherapy (NRT) has been proven effective at improving cancer related outcome measures, including overall-survival (OS) in the management of solid cancers. However, its utilisation in breast cancer has not been explored to the extent of neo-adjuvant chemotherapy (NAC). The evidence for the application of NRT in breast cancer is evaluated.MethodsPubMed, Embase and the Cochrane Library databases were searched systematically in August 2020 for studies that addressed the role of NRT in the treatment of breast cancer. Studies were deemed eligible if they reported on objective outcome measurements of OS, disease free-survival (DFS) or pathological complete response (pCR) and attained a satisfactory quality assessment.FindingsA total of 23 studies reported upon 3,766 patients who had received NRT of which 3,233 also received NAC concurrently (neo-adjuvant chemo-radiotherapy (NCRT)). The pCR values ranged from 14% to 42%, 5-year DFS 61.4% to 81% and 5-year OS 71.6% to 84.2%. Complications were confined to radiation dermatitis with no cases of implant loss reported during breast reconstruction. The application of NRCT alone showed no significant difference in OS or DFS compared to NCRT followed by surgery.InterpretationNumbers of patients receiving exclusively NRT is small. However, NCRT is oncologically safe with a low side-effect profile including preceding breast reconstruction. Potential benefits include precise cancer volume targeting, chemosensitisation, elimination of delays in adjuvant therapies and alternatives to chemotherapy in oestrogen receptor positive patients. These factors warrant further exploration within randomised controlled-trials.

Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study

SummaryBackgroundThere are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England.MethodsData were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated.FindingsAs compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53–71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89–95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8–34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19–42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17–76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020.InterpretationThe COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England.FundingCancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.

Changes in the quality of care of colorectal cancer in Estonia: a population-based high-resolution study

ObjectivesLarge disparities in colorectal cancer (CRC) management and survival have been observed across Europe. Despite recent increases, the survival deficit of Estonian patients with CRC persists, particularly for rectal cancer....

A single-center experience: management of patients with thymic epithelial tumors

BackgroundThymic epithelial tumors are rare neoplasias. There are no internationally accepted standards to treat this complex oncological disease. The studies on which our knowledge is based frequently have methodological weaknesses. If the tumor is resectable, complete surgical excision is currently the first-line therapy. Thymic epithelial tumors respond to radiation. The therapeutic benefit of adjuvant radiotherapy depends on tumor stage. To validate and improve treatment, we share our current experiences with clinical management and surgical intervention.MethodsThis single-center retrospective study included 40 patients with primarily resectable thymic epithelial tumors who underwent resection with curative intent. The survival data was collected and presented according to Kaplan-Meier. Single- and multiple predictor survival analyses were carried out using the log-rank test and Cox proportional hazards model.ResultsSingle-predictor survival analysis showed survival to be dependent on the Masaoka-Koga classification, WHO histological classification, resection status, surgical technique, and Clavien-Dindo grade for postoperative complications. Multiple predictor analysis confirms that the Masaoka-Koga stage (HR = 4.876, P = 0.032) and Clavien-Dindo grade (HR = 4.904, P = 0.011) are independent prognostic factors for survival.ConclusionIn addition to the Masaoka stage, the occurrence of severe postoperative complications represents an independent prognostic factor. Given the tumor’s sensitivity to radiation, the use of neoadjuvant radiotherapy can be considered to downstage Masaoka-Koga stages III and higher, thus reducing surgical risks. Further prospective multicenter studies are urgently needed.

Clinicopathological factors associated with positive circumferential margins in rectal cancers

Positive circumferential resections are associated with local disease recurrence and reduced survival in rectal cancer. We studied a cohort of consecutive rectal cancer resections to assess for clinicopathological differences and survival in patients with positive and negative circumferential margins. Rectal cancers were identified from a retrospective histopathology database of colorectal resections performed at five western Sydney hospitals from 2010 to 2016. Univariate and multivariate analysis with binary logistic regression were performed on histopathology data matched with survival times from the New South Wales Registry of Births Deaths and Marriages. A total of 502 rectal cancer patients were identified including 66 (13.1%) with involved circumferential margins. Patients with positive and negative circumferential margins had a similar distribution of age, gender and use of neoadjuvant radiotherapy. Tumours with involved circumferential margin comprised 98.5% T3 and T4 disease of which 51.5% received neoadjuvant radiotherapy. These were significantly associated with metastatic disease, increasing tumour size, circumferential and perforated tumours on univariate analysis. Multivariate analysis identified abdomino-perineal resection (odds ratio (OR) 3.35; P = 0.003), en-bloc multivisceral resection (OR 2.56; P = 0.032), T4 stage (OR 6.99; P < 0.001), perineural (OR 5.61; P < 0.001) and vascular invasion (OR 2.46; P = 0.022) as independent risk factors. Five-year survival was significantly worse for patients with involved circumferential margins (26% versus 69%; P < 0.001). Circumferential margin status reflects not only technical success but also aggressive disease phenotypes which require adjuvant therapy. Further work is needed to determine whether omission of radiotherapy has had an effect on long-term outcomes in some of our at-risk patients.

The management of rectal cancer in older patients in England - a retrospective population based study a patients diagnosed between April 2009 and December 2014

Background This study sought to examine the use of radical treatment for rectal cancer (neoadjuvant radiotherapy and major surgical resection) and the associated outcomes across the English National Health Service (NHS) in relation to age. Materials and Methods Data for all patients diagnosed with a first primary rectal cancer between 1st April 2009 and 31st December 2014 were included. Data from multiple sources including cancer registration data and Hospital Episode Statistics (HES) data, which were compiled as part of the Bowel Cancer Intelligence UK (BCI UK) hub, were used to obtain information about patient and tumour characteristics, treatments and outcomes. Patients were divided into three groups in relation to their age at the time of diagnosis; <70, 70-79 and ≥80. Descriptive analyses were undertaken to assess the variation in treatment and outcomes. Multilevel binary logistic regression models were used to assess the factors associated with the receipt of a major surgical resection, with patients clustered within NHS trusts. Results In total, 52,922 people were diagnosed with a first primary rectal cancer in England over the study period. Of these, 11,924 (22.4%) were aged 80 or over at the time of diagnosis. The proportion undergoing a major resection decreased with age, falling from 66.5% amongst those aged under 70 to 31.7% amongst those aged 80 and over. The use of neoadjuvant radiotherapy decreased with age, with 48.3% of those aged under 70 receiving pre-operative radiotherapy compared to 26.5% of those aged 80 and over. Stoma creation rates were similar across all age groups. However the proportion of patients having their stoma closed within 18 months fell with age, from 66.3% amongst those aged <70 to 32.4% amongst those aged ≥80. Deaths within 30 days of a major surgical resection increased with age, from 1.0% to 5.5%. The rate of returns to theatre were consistent between age groups (11.0%, 11.6% and 10.2% respectively). The rate of 30-day post-operative mortality was lower amongst those who received neoadjuvant radiotherapy than those who did not across all age groups (1.6% versus 2.6%). After adjustment for case-mix factors significant variation in operative rates for the oldest patients between NHS trusts in England remained. Results from adjusted logistic regression models showed no significant difference in 30-day post-operative mortality, length of stay or emergency readmission amongst those aged 80 and over between trusts with high and low operative rates. Conclusions This study demonstrates that older patients with rectal cancer were less likely than younger patients to receive potentially curative treatment. However those who did receive potentially curative treatment for rectal cancer demonstrated outcomes comparable to those of their younger counterparts, suggesting that they have been well selected.

Predictive value and changes of inducible nitric oxide synthase expression in patients with rectal cancer under the influence of antitumor therapy

The aim of investigation – to establish the features of iNOS expression in the rectum wall under the influence of various neoadjuvant therapy options in patients with rectal cancer (RC) and to find out its predictive significance. Materials and methods. In 88 patients with stage II–III rectal adenocarcinoma we established iNOS expression in the tumor before and after neoadjuvant radiotherapy (NRT), therapeutic pathomorphosis grade and density of immune cell infiltrates. Patients were divided into 3 groups: 1 – patients after the course of NRT on the tumor site; 2 – patients who underwent chemoradiomodification of the NRT with drug tegafur; 3 – patients who underwent chemoradiomodification of the NRT with tegafur and L-arginine. Results. In the tumors of rectal cancer the level of iNOS expression by 4.5 times exceeded that in the intact rectum wall (P < 0.001), correlated with metastatic lesion of the regional lymph nodes (r = 0.55; P = 0.026) and depended on the type of growth of RC. The level of iNOS expression in the tumor prior to treatment in Group 3 patients, in which the high efficacy of NRT was reported, was 54.61 ± 3.55 versus 35.10 ± 2.28 СU in the rest of the patients (P = 0.01). After NRT, most Groups 1–2 patients reduced the iNOS expression in the RC tissue – on the average to 37.30 ± 4.13 СU, more in the residual parenchyma as compared to the tumor stroma, while Group 1 patients showed the lowest total immunosensitivity intensity of iNOS – 24.34 ± 3.10 CU, and Group 3 patients – the highest – 45.35 ± 5.84 CU. Conclusions. After the use of NRT, iNOS expression in the residual parenchyma of the RC decreased, but in the stroma the marker expression remained unchanged or there was an increase in the marker expression, which was most inherent to therapeutic pathomorphosis grades III–IV. iNOS expression in the RC stroma was highest in patients after NRT with radiomodification using tegafur and L-arginine and positively correlated with the density of immune cell infiltrates in the tumor. Evaluation of the preoperative level of iNOS in patients with RC can serve as a predictive test of advisability of NRT used on the background of radiomodification with L-arginine.

244 (PB-039) - The use of neoadjuvant radiotherapy in high risk or locally advanced breast cancer patients prior to definitive surgery with mastectomy and autologous breast reconstruction does not impact on post operative surgical complications

244 (PB-039) - The use of neoadjuvant radiotherapy in high risk or locally advanced breast cancer patients prior to definitive surgery with mastectomy and autologous breast reconstruction does not impact on post operative surgical complications

A systematic review of neo-adjuvant radiotherapy in the treatment of breast cancer

Introduction The use of neo-adjuvant radiotherapy (NRT) has been proven effective at improving cancer related outcome measures, including overall-survival (OS) in the management of solid cancers. However, its utilisation in breast cancer has not been explored to the extent of neo-adjuvant chemotherapy (NAC). The evidence for the application of NRT in breast cancer is evaluated. Methods PubMed, Embase and the Cochrane Library databases were searched systematically in August 2020 for studies that addressed the role of NRT in the treatment of breast cancer. Studies were deemed eligible if they reported on objective outcome measurements of OS, disease free-survival (DFS) or pathological complete response (pCR) and attained a satisfactory quality assessment. Findings A total of 23 studies reported upon 3,766 patients who had received NRT of which 3,233 also received NAC concurrently (neo-adjuvant chemo-radiotherapy (NCRT)). The pCR values ranged from 14% to 42%, 5-year DFS 61.4% to 81% and 5-year OS 71.6% to 84.2%. Complications were confined to radiation dermatitis with no cases of implant loss reported during breast reconstruction. The application of NRCT alone showed no significant difference in OS or DFS compared to NCRT followed by surgery. Interpretation Numbers of patients receiving exclusively NRT is small. However, NCRT is oncologically safe with a low side-effect profile including preceding breast reconstruction. Potential benefits include precise cancer volume targeting, chemosensitisation, elimination of delays in adjuvant therapies and alternatives to chemotherapy in oestrogen receptor positive patients. These factors warrant further exploration within randomised controlled-trials.