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Introduction: The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine's effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy., Methods: Four groups of C57/Bl6 mice received 14 Gy thoracic radiation. Mice were treated with taurine or saline supplementation by gavage. After 10 days and 14 weeks of treatment, TGF-beta1 levels were measured in serum and bronchoalveolar lavage fluid (BALF). Lung collagen content was determined using hydroxyproline analysis., Results: Ten days post radiotherapy, serum TGF-beta1 levels were significantly lower after gavage with taurine rather than saline (P = 0.033). BALF TGF-beta1 at 10 days was also significantly lower in mice treated with taurine (P = 0.031). Hydroxyproline content was also significantly lower at 14 weeks in mice treated with taurine (P = 0.020)., Conclusion: This study presents novel findings of taurine's role in protecting from TGF-beta1-associated development of lung fibrosis after thoracic radiation.

Ryan R, Gibbons D, Hyland J M P, Treanor D, White A, Mulcahy H E, O'Donoghue D P, Moriarty M, Fennelly D & Sheahan K (2005) Histopathology 47, 141–146 Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer : To standardize the pathological analysis of total mesorectal excision specimens of rectal cancer following neoadjuvant chemoradiotherapy for locally advanced disease (T3/T4), including tumour regression. : Standardized dissection and reporting was used for 60 patients who underwent total mesorectal excision following long-course chemoradiotherapy. Tumour regression was scored by two pathologists (K.S., D.G.) using both an established 5-point tumour regression grade (TRG), and a novel 3-point grade. Both scores were evaluated for interobserver variability. A complete or near-complete pathological response (3-point TRG 1) was found in 10 patients (17%). Using the 5-point TRG, there was good agreement between both pathologists (κ = 0.64). Using the 3-point grade, agreement was excellent (κ = 0.84). No disease recurrence has been reported in patients with a complete, or near complete pathological response (3-point TRG 1), after a mean follow-up of 22 months. : Tumour regression grade is a useful method of scoring tumour response to chemoradiotherapy in rectal cancer. TRG 1 and 2 can be regarded as a complete pathological response (ypT0). A modified 3-point grade has the advantage of better reproducibility, with similar prognostic significance. [ABSTRACT FROM AUTHOR]

Background: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. Methods: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. Findings: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p¼ .002) but not between the pre-treatment and post-treatment pain scores. Interpretation: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients. [ABSTRACT FROM AUTHOR]

Impending malignant spinal cord compression (IMSCC) may be defined as compression of the thecal sac, without any visible pressure on the spinal cord itself. Although there is a perception that IMSCC patients have a better prognosis and less severe clinical symptoms than true malignant spinal cord compression (MSCC) patients, these factors have never been documented in the literature.PurposeTo record the characteristics, management and functional outcome of a group of patients with IMSCC, who were treated with radiotherapy in our institution, and compare these parameters with similar data on MSCC patients.Materials and methodsData (gender, age, primary oncological diagnosis, pain, performance status and neurological status) were prospectively collected for 28 patients. Patients were then followed up post treatment to document their response to treatment and treatment-related toxicity.ResultsThe median survival of our group of IMSCC patients is similar to that of an MSCC patient. In addition, the IMSCC group exhibits significant clinical symptoms including neurological deficit.ConclusionAlthough further studies are necessary, we have found that IMSCC patients in this study share similar prognosis and clinical symptoms with MSCC patients. Clinicians should be aware of this when communicating with IMSCC patients and their families, and short-course radiotherapy should be considered. [ABSTRACT FROM AUTHOR]

Radiation-induced bystander effects are the subject of intense investigation in radiation protection. The effects predominate at low doses and have been discussed mainly in terms of the impact on low-dose risk assessment. Possible therapeutic implications have been alluded to, but not discussed in any detail. The purpose of this review was to consider bystander biology in areas of major importance or interest in radiotherapy. These include consideration of radiation-induced bystander effects during the cell cycle, under hypoxic conditions, when fractionated therapy modalities are used, or when combined radiochemotherapy is given. Also discussed are individual variations in toxicity of bystander factors and normal tissue “collateral” damage. The importance of considering the tumor in the context of the organ, and even the organism that supports it, is also discussed. Direct clinical radiotherapy studies that consider bystander effects are not in the public domain at the time of writing, but many in vitro studies are available that are relevant; some preliminary animal data have also been published. Because radiation-induced bystander effects appear to challenge many of the central assumptions that underlie radiotherapy practice, it is important to consider what unexplored treatment avenues might result from a consideration of these effects. The final part of this paper is devoted to this point. [Copyright &y& Elsevier]

Purpose: Our study aims to assess the incidence of radiotherapy-induced hypothyroidism in breast cancer patients and correlate it with the mean dose to the thyroid. Method: Out of 75 patients, who were treated under 3-dimensional conformal radiotherapy field in field {3D CRT(FiF)} by conventional Radiotherapy to post-modified radical mastectomy (MRM) chest wall, a dosing regimen of 200cGy per fraction for a total 5000cGy at our center in the year 2016, 63 patients were randomized and investigated. All patients were treated by Linear accelerator, varian, with the Eclipse version 13.6 treatment planning system. All information on radiotherapy used for each patient was extracted from the Eclipse treatment planning system. All patients were followed up for 7 years after Radiotherapy. TSH and freeT4 levels were measured. The Chi-square test was used to compare the outcome of the disease in terms of nominal and rank qualitative variables. Student t-test was used to compare in terms of quantitative variables. Result: After 7 years since the radiotherapy, according to the results, a total of 10 out of 63, {15.87% (P = 0.008)} of patients had hypothyroidism, of which 11.11% (7 out of 63) were clinical, and 4.76% (3 out of 63) were subclinical. Dmean > 21 Gy compared with Dmean ≤ 21 Gy was associated with a significantly higher incidence of radiation-induced hypothyroidism (RHT) at 7 years after radiotherapy (3.17% vs. 12.7%, P<0.001). Conclusion: We recommend that the Dmean of the thyroid should be kept lower than 21Gy for post-modified radical mastectomy radiotherapy to decrease the incidence of radiation-induced hypothyroidism. Further investigations in larger cohorts are required to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy followed by radical surgery is recommended for locally advanced rectal cancer (LARC). But radiotherapy can cause potential adverse effects. The therapeutic outcomes, postoperative survival and relapse rates between neoadjuvant chemotherapy (N-CT) and neoadjuvant chemoradiotherapy (N-CRT) patients have rarely been studied. Methods: From February 2012 to April 2015, patients with LARC who underwent N-CT or N-CRT followed by radical surgery at our center were included. Pathologic response, surgical outcomes, postoperative complications and survival outcomes (including overall survival [OS], disease-free survival [DFS], cancer-specific survival [CSS] and locoregional recurrence-free survival [LRFS]) were analyzed and compared. Concurrently, the Surveillance, Epidemiology, and End Results Program (SEER) database was used to compare OS in an external source. Results: A total of 256 patients were input into the propensity score-matching (PSM) analysis, and 104 pairs remained after PSM. After PSM, the baseline data were well matched and there was a significantly lower tumor regression grade (TRG) (P < 0.001), more postoperative complications (P = 0.009) (especially anastomotic fistula, P = 0.003) and a longer median hospital stay (P = 0.049) in the N-CRT group than in the N-CT group. No significant difference was observed in OS (P = 0.737), DFS (P = 0.580), CSS (P = 0.920) or LRFS (P = 0.086) between the N-CRT group and the N-CT group. In the SEER database, patients who received N-CT had similar OS in both TNM II (P = 0.315) and TNM III stages (P = 0.090) as those who received N-CRT. Conclusion: N-CT conferred similar survival benefits but caused fewer complications than N-CRT. Thus, it could be an alternative treatment of LARC. [ABSTRACT FROM AUTHOR]

Aim: Intraoperative radiotherapy (IORT) decreases local recurrence rates for advanced rectal cancer. Nevertheless, utilization of IORT is limited due to the associated logistical and financial challenges. The aim of this study is to describe the development and delivery of a novel IORT protocol for advanced rectal cancer that overcomes these difficulties in the context of the early phase of an IDEAL 2a study. The primary outcome measure was the ability to deliver IORT using this novel protocol with IORT‐related toxicity as the secondary outcome measure. Method: Consecutive patients with advanced rectal cancer expected to have involved (R1) resection margins were enrolled. After resection, 12 Gy low‐energy photon IORT was delivered using the Axxent device with a custom‐designed elliptical spherical balloon applicator. Results: Six patients with a median age of 47 years (range 33–88 years; five women) were enrolled between 2018 and 2019. The indication was advanced cancer in four patients and atypical invasive pelvic side wall lymph nodes in two. IORT was successfully delivered in all cases. No toxicity was encountered. Three advanced cancer patients had R1 resection and one had complete resection (R0); resection margin status could not be established for the two lymph node cases. Five patients were alive at 3.4 (2.9–4.1) year follow‐up. None of the R1 cases recurred. Conclusion: This is the first study to describe a novel IORT protocol using low‐energy photon IORT for advanced rectal cancer. IORT could be delivered in all cases and no IORT‐related toxicity was encountered. Available oncological outcome data are encouraging, but further studies will be necessary to determine the oncological effectiveness of this protocol. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemoradiotherapy has been used for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal dose of radiation therapy and the effect of lymphadenectomy after neoadjuvant therapy on patient outcomes are uncertain. We retrospectively reviewed the data of patients who received neoadjuvant therapy followed by surgery for ESCC. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were compared between patients who received radiation doses of 45.0 Gy (PF4500) and 50.4 Gy (PF5040). Subgroup analysis was performed based on the number of lymph nodes removed through lymph node dissection (LND). Data from a total of 126 patients were analyzed. No significant differences were found in 3-year OS and DFS between the PF4500 and PF5040 groups (OS: 45% versus 54%, p = 0.218; DFS: 34% versus 37%, p = 0.506). In both groups, no significant differences were found in 3-year locoregional-specific DFS between patients with a total LND number ≤17 and >17 (PF4500, 35% versus 50%, p = 0.291; PF5040 group, 45% versus 46%, p = 0.866). The PF5040 and PF4500 groups were comparable in terms of survival outcomes and local control. Although no additional survival benefits were identified, the extent of LND should not be altered according to the radiation dose. [ABSTRACT FROM AUTHOR]

Purpose: The objective was to compare disease-free survival (DFS) and distant metastasis in patients with neoadjuvant chemoradiotherapy (NCRT) and total neoadjuvant therapy (TNT) for locally advanced rectal cancer. Methods: Patients with cT3-4N0M0 or cTxN1-2M0 rectal cancer were included in this retrospective study. Patients who received NCRT (radiotherapy with concurrent capecitabine) or TNT (radiotherapy with two concurrent cycles of capecitabine and oxaliplatin (CAPOX) followed by another two cycles of CAPOX) during January 2011 and November 2016 at Beijing Chaoyang Hospital, Capital Medical University were included. All patients had received radical surgery. Adverse events, pathological response and survival outcomes in the two groups were compared. Results: One hundred eighty-two patients were enrolled, 120 in the TNT and 62 in the NCRT groups. No significant between-group differences in neoadjuvant therapy-associated adverse events or surgical complications were found. TNT achieved a higher pathological complete response (pCR) rate (25.8%) compared with NCRT (12.9%, P = 0.044). Patients in the TNT group had a higher 3-year DFS rate (82.8% versus 75.7%, P = 0.041) and lower distant metastasis rate (19.2% versus 33.1%, P = 0.049) than those in the NCRT group. Multivariate analysis showed that NCRT was an independent risk factor for DFS (95%CI 2.023–13.415, P = 0.001) and distant metastasis (95% CI 2.149–20.082, P = 0.001). Conclusion: With similar adverse events and a higher pCR rate when compared with NCRT, TNT might be considered as a safe and effective therapeutic strategy to improve prognosis in patients with locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Radiotherapy is an effective regimen for cancer treatment alone or combined with chemotherapy or immunotherapy. The direct effect of radiotherapy involves radiation-induced DNA damage, and most studies have focused on this area to improve the efficacy of radiotherapy. Recently, the immunomodulatory effect of radiation on the tumour microenvironment has attracted much interest. Dying tumour cells can release multiple immune-related molecules, including tumour-associated antigens, chemokines, and inflammatory mediators. Then, immune cells are attracted to the irradiated site, exerting immunostimulatory or immunosuppressive effects. CC chemokines play pivotal roles in the trafficking process. The CC chemokine family includes 28 members that attract different immune subsets. Upon irradiation, tumour cells or immune cells can release different CC chemokines. Here, we mainly discuss the importance of CCL2, CCL3, CCL5, CCL8, CCL11, CCL20 and CCL22 in radiotherapy. In irradiated normal tissues, released chemokines induce epithelial to mesenchymal transition, thus promoting tissue injury. In the tumour microenvironment, released chemokines recruit cancer-associated cells, such as tumour-infiltrating lymphocytes, myeloid-derived suppressor cells and tumour-associated macrophages, to the tumour niche. Thus, CC chemokines have protumour and antitumour properties. Based on the complex roles of CC chemokines in the response to radiation, it would be promising to target specific chemokines to alleviate radiation-induced injury or promote tumour control. [ABSTRACT FROM AUTHOR]

Radiomics is an emerging translational field of medicine based on the extraction of highdimensional data from radiological images, with the purpose to reach reliable models to be applied into clinical practice for the purposes of diagnosis, prognosis and evaluation of disease response to treatment. We aim to provide the basic information on radiomics to radiologists and clinicians who are focused on breast cancer care, encouraging cooperation with scientists to mine data for a better application in clinical practice. We investigate the workflow and clinical application of radiomics in breast cancer care, as well as the outlook and challenges based on recent studies. Currently, radiomics has the potential ability to distinguish between benign and malignant breast lesions, to predict breast cancer's molecular subtypes, the response to neoadjuvant chemotherapy and the lymph node metastases. Even though radiomics has been used in tumor diagnosis and prognosis, it is still in the research phase and some challenges need to be faced to obtain a clinical translation. In this review, we discuss the current limitations and promises of radiomics for improvement in further research. [ABSTRACT FROM AUTHOR]

Oral nutritional supplements are widely recommended to head-and-neck cancer patients undergoing anti-cancer treatment; however, their effects on the outcomes of most importance to patients are unclear. This study aimed to systematically review the evidence of effect of oral nutritional supplements on mortality, treatment tolerance, quality of life, functional status, body weight and adverse effects. We searched PubMed, Embase, CENTRAL, LILACS, Web of Science, CINAHL, two trial registry platforms, three sources of grey literature and reference lists of included studies. We assessed the risk of bias using the revised Cochrane risk-of-bias tool (RoB 2), and certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We used random-effects models with Hartung–Knapp correction for the meta-analyses. We included fifteen trials, of which five were ongoing or unpublished, providing evidence in four comparisons. We found very low to low certainty evidence for the effect of oral nutritional supplements on mortality, treatment tolerance, quality of life, functional status and adverse effects. When compared with nutritional counselling alone, nutritional counselling plus oral nutritional supplements probably increased body weight slightly. We also found adverse events relating to supplements use such as nausea, vomiting and feeling of fullness. Possible increases in mortality, treatment tolerance and quality of life besides a possible decrease in functional status are worthy of further investigation. Future research could attempt to address the clinical importance of a probable increase in body weight. Possible adverse effects of the use of oral nutritional supplements should not be overlooked. [ABSTRACT FROM AUTHOR]

Background and Purpose: Dyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry. Material and Methods: Eighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters. Results: The median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment. Conclusions: Worsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits. [ABSTRACT FROM AUTHOR]

Background: Transanal total mesorectal excision (TaTME) seems to be a valid alternative to the open or laparoscopic TME. Quality of the TME specimen is the most important prognostic factor in rectal cancer. This study shows the pathological results of the largest single-institution series published on TaTME in patients with mid and low rectal cancer.Methods: We conducted a retrospective cohort study of all consecutive patients with rectal cancer, treated by TaTME between November 2011 and June 2016. Patient data were prospectively included in a standardized database. Patients with all TNM stages of mid (5-10 cm from the anal verge) and low (0-5 cm from the anal verge) rectal cancer were included.Results: A total of 186 patients were included. Tumor was in the mid and low rectum in, respectively, 62.9 and 37.1%. Neoadjuvant chemoradiotherapy was given in 62.4%, only radiotherapy in 3.2%, and only chemotherapy in 2.2%. Preoperative staging showed T1 in 3.2%, T2 in 20.4%, T3 in 67.7%, and T4 in 7.5%. Mesorectal resection quality was complete in 95.7% (n = 178), almost complete in 1.6% (n = 3), and incomplete in 1.1% (n = 2). Overall positive CRM (≤ 1 mm) and DRM (≤ 1 mm) were 8.1% (n = 15) and 3.2% (n = 6), respectively. The composite of complete mesorectal excision, negative CRM, and negative DRM was achieved in 88.1% (n = 155) of the patients. The median number of lymph nodes found per specimen was 14.0 (IQR 11-18).Conclusions: The present study showed good rates regarding total mesorectal excision, negative circumferential, and distal resection margins. As the specimen quality is a surrogate marker for survival, TaTME can be regarded as a safe method to treat patients with rectal cancer, from an oncological point of view. [ABSTRACT FROM AUTHOR]

Due to biocompatibility and relative non-toxic nature, gold nanoparticles (GNPs) have been studied widely to be employed in radiotherapy as radio-sensitizer. On the other hand, they may enhance radiation-induced bystander effect (RIBE), which causes radiation adverse effects in non-irradiated normal cells. The present study was planned to investigate the possibility of augmenting the RIBE consequence of applying glucose-coated gold nanoparticles (Glu-GNPs) to target cells. Glu-GNPs were synthesized and utilized to treat MCF7 and QUDB cells. The treated cells were irradiated with 100 kVp X-rays, and their culture media were transferred to non-irradiated bystander cells. Performing MTT cellular proliferation test and colony formation assay, percentage cell viability and survival fraction of bystander cells were determined, respectively, and were compared to control bystander cells which received culture medium from irradiated cells without Glu-GNPs. Glu-GNPs decreased the cell viability and survival fraction of QUDB bystander cells by as much as 13.2 and 11.5 %, respectively ( P < 0.02). However, the same end points were not changed by Glu-GNPs in MCF-7 bystander cells. Different RIBE responses were observed in QUDB and MCF7 loaded with Glu-GNPs. Glu-GNPs increased the RIBE in QUDB cells, while they had no effects on RIBE in MCF7 cells. As opposed to QUDB cells, the RIBE in MCF7 cells did not change in the dose range of 0.5-10 Gy. Therefore, it might be a constant effect and the reason of not being increased by Glu-GNPs. [ABSTRACT FROM AUTHOR]

Background: Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC.Methods: Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied.Results: After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%.Conclusion: For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols.Trial Registration: NCT02720614, the date of registration: March 23, 2016. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated three-dimensional conformal radiation therapy (3D-CRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically unable to tolerate surgery and who are not amenable to treatment with stereotactic body radiotherapy. This study assessed the efficacy and safety of 3D-CRT as a monotherapy in patients with localized stage T2 or T3 NSCLC.Methods: This retrospective study consisted of 29 patients (20 males) aged 56-89 years (median, 76 years) with histologically confirmed NSCLC who underwent 3D-CRT between 2005 and 2014.Results: The median duration of patient observation was 17.0 months (range, 1.0-64.0 months). Complete and partial responses occurred in 13.8 and 44.8 % of patients, respectively, and the overall response rate was 58.2 %. Meanwhile, the 1- and 3-year survival rates were 65.8 and 33.8 %, respectively. In T2 NSCLC, the median survival time (MST) was 12 months, and the 1- and 3-year survival rates were 62.4 and 21.4 %, respectively. In T3 NSCLC, the MST was 17 months, and the 1- and 3-year survival rates were 72.9 and 48.6 %, respectively. Severe toxicities (Common Terminology Criteria Grade 3) were not observed. The mean biologically effective dose required to improve local control exceeded 80 Gy (range, 67.2-96.0 Gy).Conclusion: These findings support a role for 3D-CRT as a treatment option for patients who refuse or could not tolerate surgical therapy with early-stage NSCLC. Although this was a small, retrospective study, it may form the basis for future, larger controlled studies on 3D-CRT as a monotherapy for NSCLC. [ABSTRACT FROM AUTHOR]

Aim: The efficacy of neoadjuvant chemotherapy without radiation (NAC) in the treatment of rectal cancer remains unclear. This retrospective study was aimed at determining the pathological complete response rate and short-term outcomes of NAC in patients with locally advanced rectal cancer. Patients and Methods: We collected data on 159 consecutive patients treated for rectal cancer (cT3/cT4a, cN+, and cM0 status) at five tertiary referral hospitals between 2005 and 2010. Pathological complete response (pCR) and safety were assessed as the main outcomes in 124 eligible patients comprising 15 who received NAC (NAC group) and 109 who received no neoadjuvant chemotherapy (non-NAC group). Results: In the NAC group, 2 patients (13.3%) achieved a pCR (95% confidence interval: 1.7-40.5%) and 3 patients (20%) experienced grade 3/4 adverse events. No significant differences were found between the NAC and non-NAC groups in terms of short-term outcomes, including R0 proportion (100 vs. 96.3%, p = 0.45) and postoperative grade 3/4 complications (13.3 vs. 18.4%, p = 0.63). Conclusions: Neoadjuvant systemic chemotherapy without radiation appears to be safe, without worsening short-term outcomes, in patients with locally advanced rectal cancer. A further study is needed to verify these findings in larger samples. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There is much debate around the preoperative treatment of colorectal cancer and, in particular, neoadjuvant chemoradiotherapy in locally advanced rectal cancer. This treatment carries a significant risk of harmful side effects and has a highly variable response rate. Predictive biomarkers have been the subject of a great deal of study with the aim of pretreatment risk stratification in order to more accurately determine which patients will derive the most benefit and least harm from these treatments. The study of epigenetics in colorectal cancer is relatively recent, and distinct patterns of aberrant DNA methylation, in particular the cytosine-phosphate-guanine (CpG) island methylator phenotype (CIMP), have been demonstrated in colorectal cancer, and their characterisation and significance are under debate, particularly in rectal cancer. These patterns of DNA methylation have been associated with differences in response to therapy and treatment outcomes and therefore have the potential to be used as biomarkers in tailored therapy regimes for patients with rectal cancer. This review aims to summarise the current state of the art in rectal cancer, with particular regard to the determination of DNA methylation patterns, the CpG island methylator phenotype and its potential as a novel biomarker in rectal cancer treatment and prediction of outcomes and response after neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Quality of life (QoL) is one of the most important outcomes in cancer care. Although a number of instruments to measure health-related QoL (HRQoL) exist, there are few suitable instruments to measure individual QoL. The best established instrument is the Schedule for the Evaluation of Individual Quality of Life (SEIQoL). The disadvantage of this questionnaire is its use of semi-structured interviews, which are very time-consuming. The purpose of our study was to transform the SEIQoL into an economical instrument that can be used in clinical trials with large samples. Methods: We developed the SEIQoL-Questionnaire (SEIQoL-Q) on the basis of the SEIQoL-Direct Weighting (SEIQoL-DW) by transforming the interview guide into a written questionnaire. Patients ( N = 1,108) in all three phases of radiation treatment (first consultation, ongoing irradiation, and aftercare) were asked to complete the SEIQoL-Q and the European Organization for Research and Treatment of Cancer QLQ-C30. Results: While the average HRQoL measured by the QLQ-C30 was 55.6, the average SEIQoL-Q index was 59.6. The most important life domain was 'physical health,' followed by 'emotional well-being' and 'family.' Patients attributed the highest level of satisfaction to 'home/housing,' followed by 'family' and 'partnership.' Male patients were shown to have a significantly better QoL than females. The SEIQoL-Q index correlates moderately with the QLQ-C30 functioning scale 'global quality of life' [ r = .42 ( p < .001)]. Conclusions: According to our findings, the SEIQoL-Q appears to be a feasible and economical instrument for use in quantitative research among cancer patients in different stages of their disease. [ABSTRACT FROM AUTHOR]

Background The subdivision of T3 in rectal carcinoma according to the depth of invasion into perirectal fat has been recommended in the TNM Supplement since 1993. This study assessed the prognostic impact of this pathological staging in tumours removed after neoadjuvant chemoradiotherapy ( ypT3). Methods Data from patients with ypT3 rectal carcinoma (less than 12 cm from the anal verge) treated with neoadjuvant chemoradiation and total mesorectal excision were analysed. Tumour category ypT3 was subdivided into ypT3a (5 mm or less) and ypT3b (more than 5 mm), based on histological measurements of maximal tumour invasion beyond the outer border of the muscularis propria. Results Important differences between ypT3a (81 patients) and ypT3b (43) were found in 5-year rates of locoregional recurrence (7 versus 18 per cent; P = 0·049), distant metastasis (20 versus 41 per cent; P = 0·002), disease-free survival (73 versus 47 per cent; P = 0·001), overall survival (79 versus 74 per cent; P = 0·036) and cancer-related survival (81 versus 74 per cent; P = 0·007). In Cox regression analyses, the ypT3 subclassification was identified as an independent prognostic factor for disease-free ( ypT3b: hazard ratio ( HR) 2·13, 95 per cent confidence interval 1·16 to 3·89; P = 0·014), observed ( ypT3b: HR 2·02, 1·05 to 3·87; P = 0·035) and cancer-related ( ypT3b: HR 2·46, 1·20 to 5·04; P = 0·014) survival. Extramural venous invasion was found to be an additional prognostic factor, but the pathological node category after chemoradiotherapy ( ypN) did not influence survival. Conclusion In ypT3 rectal carcinomas, the proposed subclassification is superior to ypN in predicting prognosis. [ABSTRACT FROM AUTHOR]

Background: Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC. Methods: Untreated patients with unresectable stage IIIA/IIIB NSCLC or patients with a recurrence of NSCLC received accelerated hypofractionated three-dimensional conformal radiotherapy. The total dose was greater than or equal to 60 Gy. The accelerated hypofractionated radiotherapy was conducted once daily at 3 Gy/fraction with 5 fractions per week, and the radiotherapy was completed in 5 weeks. In addition to radiotherapy, the patients also received at least 1 cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. Results: A total of 26 patients (19 previously untreated cases and 7 cases of recurrent disease) received 60Gy-75Gy radiotherapy with concurrent chemotherapy. All of the patients underwent evaluations for toxicity and preliminary therapeutic efficacy. There were no treatment-related deaths within the entire patient group. The major acute adverse reactions were radiation esophagitis (88.5%) and radiation pneumonitis (42.3%). The percentages of grade III acute radiation esophagitis and grade III radiation pneumonitis were 15.4% and 7.7%, respectively. Hematological toxicities were common and did not significantly affect the implementation of chemoradiotherapy after supportive treatment. Two patients received high dose of 75 Gy had grade III late esophageal toxicity, and none had grade IV and above. Grade III and above late lung toxicity did not occur. Conclusion: High-dose accelerated hypofractionated three-dimensional conformal radiotherapy with a dose of 60 Gy or greater with concurrent NVB and CBP chemotherapy might be feasible. However esophagus toxicity needs special attention. A phase I trial is recommended to obtain the maximum tolerated radiation dose of accelerated hypofractionated radiotherapy with concurrent chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Accelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated repopulation of tumour cells during radiotherapy. This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the optimal fractionation scheme remains uncertain. The purpose of this phase I trial was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered in combination with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for unresectable stage III NSCLC. Methods: Previously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week. The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity (DLT). The MTD was regarded as the dose that was one step below the dose at which DLT occurred. Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. Results: A total of 13 patients were enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and 72 Gy. No treatment-related deaths occurred. The major adverse events included radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue, and anorexia were commonly observed, although the magnitude of these events was typically relatively minor. Among the entire group, four instances of DLT were observed, including two cases of grade 3 radiation oesophagitis, one case of grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the DLT dose level, and the lower dose of 69 Gy was regarded as the MTD. Conclusions: For unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy. The toxicity of this chemoradiotherapy regimen could be tolerated. A phase II trial is recommended to further evaluate the efficacy and safety of this regimen. [ABSTRACT FROM AUTHOR]

Background: Local excision of rectal cancer after neoadjuvant chemoradiotherapy (CRT) has been proposed as an alternative to radical surgery in selected patients. However, little is known about the significance of the morphological and histological features of residual tumour. Methods: Patients who had undergone CRT at the authors' institution between 1997 and 2010 were identified. Multiple features were assessed as putative markers of pathological response. These included: gross residual disease, diameter of residual mucosal abnormalities, tumour differentiation, presence of lymphovascular/perineural invasion and lymph node ratio. Results: Data from 220 of 276 patients were suitable for analysis. Diameter of residual mucosal abnormalities correlated strongly with pathological tumour category after CRT (ypT) ( P < 0·001). Forty of 42 tumours downstaged to ypT0/1 had residual mucosal abnormalities of 2·99 cm or less after CRT. Importantly, 19 of 31 patients with a complete pathological response had evidence of a residual mucosal abnormality consistent with an incomplete clinical response. The ypT category was associated with both pathological node status after CRT ( P < 0·001) and lymph node ratio ( P < 0·001). Positive nodes were found in only one of 42 patients downstaged to ypT0/1. The risk of nodal metastases was associated with poor differentiation ( P = 0·027) and lymphovascular invasion ( P < 0·001). Conclusion: In this series, the majority of patients with a complete pathological response did not have a complete clinical response. In tumours downstaged to ypT0/1 after CRT, residual mucosal abnormalities were predominantly small and had a 2 per cent risk of positive nodes, thus potentially facilitating transanal excision. The presence of adverse histological characteristics risk stratified tumours for nodal metastases. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyse the feasibility and determine the benefits of MRI-based pre-planning with CT/MRI data fusion in patients with cervical cancer treated with radical radiotherapy. Methods: Patients underwent MRI examination prior to external beam radiotherapy and prior to the first and fourth fraction of brachytherapy with applicators in place. Insertion of applicators at the radiology department was performed under paracervical anaesthesia. The benefit of MRI pre-planning was determined by comparing conventional treatment planning with dose specification to "point A" and dose specification to 90% of the high-risk clinical target volume (HR-CTV D90). Tolerance of MRI evaluation with applicators, coverage of HR-CTV and dose-volume parameters for organs at risk (OAR) has been assessed in 42 brachytherapy procedures. Results: Insertion of applicators at the radiology department was successful in all patients and there were no complications. The target dose was higher for MRI planning than for conventional planning (5.3 Gy vs 4.5 Gy). Maximum doses in the bladder and rectum were significantly lower (p<0.05) for MRI planning than for the conventional approach (6.49 Gy vs 7.45 Gy for bladder; 4.57 Gy vs 5.06 Gy for rectum). We found no correlation between the International Commission on Radiation Units (ICRU) point dose for OAR and the maximum dose in OAR. Nevertheless, a strong correlation between the maximum dose in OAR and the minimal dose in a volume of 2 cm³ has been observed. Conclusion: MRI-based pre-planning with consecutive CT/MRI data fusion is feasible and safe, with the advantage of increasing the dose to the tumour and decreasing the dose to the organs at risk. [ABSTRACT FROM AUTHOR]

Study aim: Many quality-of-life assessment tools are not feasible in palliative care settings because of the severe impairment of the physical, cognitive, and psychological status of patients. This study investigated whether comprehensive instruments can be replaced by a single item concerning the well-being of patients. Methods: From April to December 2008 patients receiving palliative care in three different settings (palliative care unit, inpatient unit of the department of radiotherapy, inpatient hospice) were asked to answer the assessment tools Functional Assessment of Chronic Illness Treatment (FACIT-G), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), Schedule for the Evaluation of the Individual Quality of Life (SEIQoL), and the Minimal Documentation System (MIDOS) including a single item on well-being. Correlations of sum and specific domain scores were used for correlational analysis. Results: Datasets of 72 patients were collected. The MIDOS single item on well-being correlated significantly with the QoL indexes of the EORTC (Spearman rank correlation r = −0.563) and FACIT-G (0.527). SEIQoL had low to moderate correlations with the other assessment tools. Subscales on physical functioning from the FACIT-G ( r = 0.583) and the EORTC-QLQ-C30 ( r = 0.385) had the highest correlation with the single item on well-being. Well-being correlated higher with nonphysical subscales of the QoL instruments for patients in the palliative care unit than in the radiotherapy department. Conclusions: The single item is unable to completely replace comprehensive questionnaires, but it is useful to initiate communication on QoL and can be recommended as a substitute for physical-functional aspects of QoL assessment in the palliative care setting. [ABSTRACT FROM AUTHOR]

Local recurrence after resection of rectal cancer is usually regarded as being due to a 'failure' of surgery. The completeness of resection of the mesorectum has been proposed as an indicator of the 'quality' of the resection. We determined the prognostic value of macroscopic evaluation of rectal cancer resection specimens and the circumferential resection margin (CRM) after curative surgery. From 1999 to 2006, the macroscopic quality of the mesorectum and the CRM were prospectively assessed in 127 patients who underwent rectal cancer resection with curative intent (R0+R1). Chemoradiotherapy was administered for 61 tumours staged as locally advanced tumours (T3, T4 and N+). Univariate analysis of time to local recurrence and cancer-free survival were tested (Kaplan-Meier) and multivariate analysis calculated with a Cox regression model. The mesorectum was incomplete in 34 (26.8%) patients. At a median follow up of 34 months (range, 9-96 months), in the group with an adequate mesorectal excision, the cumulative risk of local recurrence at 5 years was 10%. This was 25% if the mesorectum was incomplete ( P < 0.01). Five-year cancer-free survival was 65% if the mesorectal excision was adequate and 47% if it was not ( P < 0.05). Multivariate analysis identified T status, the CRM and the mesorectal score as independent factors for local recurrence, and T and N status and the mesorectal score as independent factors for disease-free survival. The outcome of surgical treatment of rectal cancer is related to the completeness of mesorectal excision. It is a more discriminative prognostic factor than the classic tumour-node-metastasis (TNM) system. [ABSTRACT FROM AUTHOR]

Background: A complete pathological response occurs in 10-30 per cent of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy (CRT). The standard of care has been radical surgery with high morbidity, risks and the challenges of stomata despite the favourable prognosis. This review assessed minimalist approaches (transanal excision or observation alone) to tumours with a response to CRT. Methods: A systematic review was performed using PubMed and Embase databases. Keywords included: 'rectal ', 'cancer', 'transanal', 'conservative', 'complete pathological response', 'radiotherapy and 'neoadjuvant'. Original articles from all relevant listings were sourced. These were hand searched for further articles of relevance. Main outcome measures assessed were rates of local recurrence and overall survival, and equivalence to radical surgery. Results: Purely conservative 'watch and wait' strategies after CRT are still controversial. Originally used for elderly patients or those who refused surgery, the data support transanal excision of rectal tumours showing a good response to CRT. A complete pathological response in the T stage (ypT0) indicates < 5 per cent risk of nodal metastases. Conclusion: Rectal tumours showing an excellent response to CRT may be suitable for local excision, with equivalent outcomes to radical surgery. This approach should be the subject of prospective clinical trials in specialist centres. [ABSTRACT FROM AUTHOR]

Purpose: Radioactive atoms attached to monoclonal antibodies are used in radioimmunotherapy to treat cancer while limiting radiation to healthy tissues. One limitation of this method is that only one radioactive atom is linked to each antibody and the deposited dose is often insufficient to eradicate solid and radioresistant tumors. In a previous study, simulations with the Monte Carlo N-Particle eXtended code showed that physical doses up to 50 Gy can be delivered inside tumors by replacing the single radionuclide by a radioactive nanoparticle of 5 nm diameter containing hundreds of radioactive atoms. However, tumoral and normal tissues are not equally sensitive to radiation, and previous works did not take account the biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells. Methods: The idea is to adapt the linear-quadratic expression to the tumor model and to determine biological effective doses (BEDs) delivered through and around a tumor. This BED is then incorporated into a Poisson formula to determine the shell control probability (SCP) which predicts the cell cluster-killing efficiency at different distances “r” from the center of the tumor. BED and SCP models are used to analyze the advantages of injecting radioactive nanoparticles instead of a single radionuclide per vector in radioimmunotherapy. Results: Calculations of BED and SCP for different distances r from the center of a solid tumor, using the non-small-cell lung cancer as an example, were investigated for 90Y2 O3 nanoparticles. With a total activity of about 3.5 and 20 MBq for tumor radii of 0.5 and 1.0 cm, respectively, results show that a very high BED is deposited in the well oxygenated part of the spherical carcinoma. Conclusions: For either small or large solid tumors, BED and SCP calculations highlight the important benefit in replacing the single β-emitter 90Y attached to each antibody by a 90Y2 O3 nanoparticle. [ABSTRACT FROM AUTHOR]

Background/Purpose. The benefit of whole brain radiotherapy (WBRT) for RTOG RPA (Radiation Therapy Oncology Group Recursive Partitioning Analysis) class 3 patients with brain metastases is not well established. The aim of this study was to determine whether WBRT has any benefit in terms of symptoms palliation in such patients. Evaluation of patients’ preferences for WBRT, changes in performance and neurological status were secondary aims. Methods. Ninety-one RTOG RPA class 3 patients were included. All patients received WBRT (20 Gy in 5 fractions) and were asked to complete a questionnaire about their symptoms before and one month after WBRT. The patient's symptom checklist comprised 17 items scored from 0 to 3; a higher score meant a greater symptom intensity. The mean scores at baseline and after treatment were compared. Karnofsky performance status (KPS) and neurological status before and one month after WBRT were also recorded. Patients were asked to express their preference as to the WBRT undergone. Results. Forty-three (47%) patients completed both symptom checklists. The mean scores on the symptom checklist were 18.21 and 21.09 at baseline and one month after WBRT, respectively (p = 0.02). The KPS was estimated after WBRT in 42 patients: 57% of patients improved, 26% worsened, and 17% did not change from the baseline KPS score (p = 0.06). Neurological status did not change from baseline to one month after WBRT (p = 0.44). Only 7% of respondents would not have consented to the WBRT undergone. Conclusion. Our results challenge the palliative value of the WBRT in RPA class 3 patients. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the effect of two different time intervals between radiation therapy and surgery for rectal cancer on the histological tumor regression grade (TRG) in the resected specimen. Between 1995 and 2000, patients undergoing preoperative radiation therapy and TME for locally advanced (T3N0 and T3N1) mid and low rectal tumors treated in the VU University Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment (5 × 5 Gy) in the VU University medical center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6–8 weeks in the VU University Medical Center (LI group). All available histological material was reevaluated for TRG and correlated to survival. Sixty-seven patients were included in the present study, 28 in the LI group and 39 in the SI group. Patient gender was comparable for both groups with 21 (75%) male patients in the LI group versus 26 (67%) male patients in the SI group ( p = 0.46). A T3N0 preoperative tumor stage was found in 21 (75%) patients in the LI group and in 33 (85%) patients in the SI group ( p = 0.36). All tumors were histologically proven adenocarcinoma. Patients in the SI group were significantly older (67 vs. 58 years). In the LI group, a significantly more pronounced histological tumor regression was found. A complete response (TRG1), combined with a near complete histological response (TRG 2), were present in 12 patients in the LI group and in four patients in the SI group ( p = 0.002). Radicality of resection was comparable for both groups. With a follow-up of over 60 months, there were no statistically significant differences between the SI and LI groups regarding local control, overall, or disease-free survival. Although histological tumor regression is significantly more pronounced following a long interval between radiation therapy and surgery, in the present study, this is not reflected in a better radical resection rate, local control or better overall and disease-free survival. [ABSTRACT FROM AUTHOR]

Objective The reduction in tumour stage induced by full course radiotherapy plus chemotherapy is apparent from histological changes. The purpose of this study was to determine the rate of complete pathological response and to evaluate the prognostic value for disease free survival (DFS) and disease specific survival (DSS) of the response. The relation between pretreatment variables (age, gender, stage, tumour height and [carcinoembryogenic antigen (CEA)] and postsurgical variables was compared to the pathological response. Method A total of 119 patients with stage II or III rectal cancer underwent surgery 6 weeks after neoadjuvant treatment. Group A included patients with a complete or good pathological response (Mandard grade I–II) and group B patients with a poor response (Mandard grade III–IV–V).The pretreatment endo-rectal ultrasound scan stage was compared with histopathology stage of the resected specimen. DFS and DSS were compared using the log-rank test. Results All 119 patients (mean age 67.9 years, 83 males) underwent resection. The tumour was located in the upper, middle and lower third of the rectum in 11, 51 and 57 patients. 88 patients had a low anterior resection, 28 patients abdomino-perineal resection and three a Hartmann’s operation. There was no postoperative death. The circumferential margin (CM) was involved in 10%. A complete pathological response was observed in 17 (14.2%) patients. Thirty-six (30.2%) patients had a group A and 83 a group B response. Group A showed DFS to be significantly higher than group B (log rank: P = 0.007). The DSS rate was not significantly different between the two groups (log rank P = 0.113). Down-staging was not related with DFS. No relation was found between pretreatment variables and response. A good pathological response was related to a lower rate of permanent colostomy but not with CM involvement or the number of lymph nodes. Conclusion Tumour regression of grades I or II was a good indicator of DFS in locally advanced rectal cancer, treated by neoadjuvant chemotherapy and radiotherapy. Patients with a high regression grade were associated with a lower incidence of definitive stoma formation. The regression grade was shown to be a better prognostic factor than down-staging. [ABSTRACT FROM AUTHOR]

The article provides information on the guidelines for the nutritional management of patients receiving a radiation therapy developed by Steering Committee of dietitians. It states that the guidelines feature clinical questions related to the dietetic management of adult patients with cancer to provide dietitians in Australia and New Zealand. The guidelines can be used as a framework to decision making. Further, the Dietitians Association of Australia (DAA) endorsed the guidelines.

Purpose: pentoxifylline (PTX) and tocopherol (vitamin E) are antioxidants previously shown to be useful in combination in the treatment of late radiation induced toxicity. The purpose of this study was to investigate the benefit of combination therapy with carbogen pentoxifylline and tocopherol in the mitigation of late radiation effects. As the optimal duration of PTX and tocopherol treatment has not been fully established, we studied short versus extended treatment duration. Methods: we conducted a phase II prospective randomized study of short versus prolonged treatment with pentoxifylline (800 mg) and tocopherol (1000 IU) orally once daily in patients with grade three toxicity post-radical radiotherapy. In addition, all 18 patients received inhaled carbogen (95% O + 5% CO2) over 90 minutes, five days/week, for three weeks. The primary end point was improved in maximum Lent-Soma toxicity scores. Results: maximum Lent-Soma scores improved in six of the 18 patients (response rate 33%). The proportion of patients responding to treatment in the prolonged treatment arm B was more than double than in the shorter arm A, but this did not reach statistical significance (p=0.321). Two patients who had prolonged treatment (arm B) had complete resolution of their symptoms, which was maintained at two and three year follow-ups. Conclusions: we recommend prolonged treatment for 12 months, with PTX and tocopherol in combination with carbogen therapy, in the management of late radiation effects. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to determine the impact of illness characteristics and psychopathological comorbidity on the quality of life (QoL) of radio-oncological patients in health-related and individual dimensions. Sixty-three of 93 eligible patients (40 women and 23 men) were included in the study during their radiation therapy visit to an outpatient centre annexed to a community hospital in Southern Bavaria, Germany. In a semi-structured interview, we elicited individually relevant life domains rated by the patients according to the ‘Schedule for the Evaluation of Individual Quality of Life – Direct Weighting’. In addition, the participants completed the ‘European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30’ and the ‘Hospital Anxiety and Depression Scale’. We also assessed the demand for psychotherapy and utilization of psycho-oncological services. In total, 9.5% of the examined patients suffer from clinically relevant anxiety and/or depression [total Hospital Anxiety and Depression Scale (HADS) score >19]. There was a weak positive correlation between Karnofsky’s Performance Status and QoL. Anxiety and depression were significantly correlated with impaired QoL, especially with impaired individual QoL. There was no association between psychopathological comorbidity and the requirement for psycho-oncological support. Conversely, patients who report difficulties in accepting help had a significantly lower QoL. Psychopathological comorbidity has a considerable influence on QoL of patients undergoing radiotherapy. Measuring the individual QoL appears as an adapted needs assessment and helps the psychotherapist in focusing on the patient’s problems and desires. Furthermore, the patient’s QoL is a main target in providing or planning mental health care in non-university oncological services. [ABSTRACT FROM AUTHOR]

: IntroductionChemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined.: Materials and methodsC57B16 mice were inoculated with 1 × 106 Lewis lung carcinoma cells into the flank and randomized to 1 of 10 treatment groups when tumor volume approached 1000 mm3. Animals received combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel density, and serum VEGF were determined.: ResultsMean (SEM) tumor volume in the chemoradiotherapy group was 762 (212) mm3 versus 565 (79) mm3 in the chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition of genistein produced a significant reduction in tumor microvessel density (P = 0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving chemoradiation alone.: ConclusionThis study provides proof of principle that chemoradiation can be enhanced by the addition of an antiangiogenic agent to the regime and suggests that further examination of such regimes is warranted. [Copyright &y& Elsevier]

Local tumour control by radiotherapy requires the complete sterilization of all tumour 'stem' cells in the tumour volume. Neither bystander effect nor radiation-induced genomic instability is able to contribute substantially to the probability of local tumour control of the primary cancer by radiotherapy. However, the progeny of these surviving tumour 'stem' cells are likely to suffer from radiation-induced genomic instability, which results in the persistent appearance of non-stem cells, i.e. a reduced probability of self-maintenance. This results in a slower growth rate of the recurrent tumour, a reduced stem-cell fraction and, as a consequence, an increased radiosensitivity of the recurrent tumour. In some recurrent tumours, particularly those that develop very late and grow very slowly, radiosensitivity may be further increased by increased intrinsic radiosensitivity, which could be related to the as yet poorly defined phenotype of 'small colony formation'. [ABSTRACT FROM AUTHOR]

We previously found that 40% of breast cancer patients showed enhanced sensitivity to X-ray induced chromosome damage in G[SUB2] lymphocytes and suggested that this might indicate a low penetrance predisposition to breast cancer, for which there is good epidemiological evidence. We have now tested the hypothesis that elevated G[SUB2] radiosensitivity is a marker of such predisposition to other common cancers. We tested patients with colorectal cancer, for which there is also good epidemiological evidence of inherited risk in a substantial proportion of cases, and patients with cancers having a strong environmental aetiology (lung and cervix). We also repeated our study of breast cancer cases and tested patients with chronic diseases other than cancer. The results support our hypothesis, in that 30% (12/37) of colorectal cases showed enhanced sensitivity compared with 9% (6/66) of normal healthy controls (P = 0.01), whereas the proportions of sensitive cervix (11%, 3/27, P = 0.72) and lung cancer cases (23%, 8/35, P = 0.07) were not significantly above normals. We confirmed the enhanced sensitivity of 40% (12/31, P = 0.001) of breast cancer patients and found that patients with non-malignant disease had a normal response in the assay (12%, 4/34, P = 0.73. We suggest that enhanced G[SUB2] chromosomal radiosensitivity is a consequence of inherited defects in the ability of cells to process DNA damage from endogenous or exogenous sources, of a type that is mimicked by ionizing radiation, and that such defects predispose to breast and colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS).Methods/design: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks.Discussion: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses.Trial Registration: Clinicaltrials.gov NCT04043156. Registered 30-07-2019. [ABSTRACT FROM AUTHOR]

Normal tissue damages induced by radiation therapy remain dose-limiting factors in radiation oncology and this is still true despite recent advances in treatment planning and delivery of image-guided radiation therapy. Additionally, as the number of long-term cancer survivors increases, unacceptable complications emerge and dramatically reduce the patients' quality of life. This means that patients and clinicians expect discovery of new options for the therapeutic management of radiation-induced complications. Over the past four decades, research has enhanced our understanding of the pathophysiological, cellular and molecular processes governing normal tissue toxicity. Those processes are complex and involve the cross-talk between the various cells of a tissue, including fibroblasts, endothelial, immune and epithelial cells as well as soluble paracrine factors including growth factors and proteases. We will review the translatable pharmacological approaches that have been developed to prevent, mitigate, or reverse radiation injuries based upon the targeting of cellular and signalling pathways. We will summarize the different steps of the research strategy, from the definition of initial biological hypotheses to preclinical studies and clinical translation. We will also see how novel research and therapeutic hypotheses emerge along the way as well as briefly highlight innovative approaches based upon novel radiotherapy delivery procedures. [ABSTRACT FROM AUTHOR]

Background: Local progression-free survival (LPFS = stable or improved motor function/resolution of paraplegia during RT without in-field recurrence following RT) is important when treating metastatic spinal cord compression (MSCC). An instrument to estimate LPFS was created to identify patients appropriately treated with short-course RT instead of longer-course RT plus/minus decompressive surgery.Methods: In 686 patients treated with 20 Gy in 5 fractions alone, ten characteristics were retrospectively analyzed for LPFS including age, interval between tumor diagnosis and RT of MSCC, visceral metastases, other bone metastases, primary tumor type, gender, time developing motor deficits, pre-RT gait function, number of vertebrae affected by MSCC, and performance score. Characteristics significantly (p < 0.05) associated with LPFS on multivariate analyses were incorporated in the scoring system. Six-month LPFS rates for significant characteristics were divided by 10, and corresponding points were added.Results: On multivariate analyses, visceral metastases (p < 0.001), tumor type (p = 0.009), time developing motor deficits (p < 0.001) and performance score (p = 0.009) were associated with LPFS and used for the scoring system. Scores for patients ranged between 24 and 35 points. Three groups were designed: 24-28 (A), 29-31 (B) and 32-35 (C) points. Six-month LPFS rates were 46, 69 and 92%, 12-month LPFS rates 46, 63 and 83%. Median survival times were 2 months (61% died within 2 months), 4 months and ≥ 11 months (median not reached).Conclusions: Most group A patients appeared sub-optimally treated with 20 Gy in 5 fractions. Patients with survival prognoses ≤2 months may be considered for best supportive care or single-fraction RT, those with prognoses ≥3 months for longer-course RT plus/minus upfront decompressive surgery. Many group B and most group C patients achieved long-time LPFS and appeared sufficiently treated with 20 Gy in 5 fractions. However, based on previous data, long-term survivors may benefit from longer-course RT. [ABSTRACT FROM AUTHOR]

The article discusses a study which proposed local excision of rectal cancer after neoadjuvant chemoradiotherapy (CRT) as an alternative to radical surgery in selected patients. The study identified patients who had undergone CRT between 1997 and 2010. It found that the diameter of residual mucosal abnormalities correlated with pathological tumour category after CRT. It also concluded that the presence of adverse histological characteristics risk stratified tumours for nodal metastases.