Short-term Radiotherapy Research Articles

Number of lymph nodes retrieved in patients with locally advanced rectal cancer after total neoadjuvant therapy: post-hoc analysis from the STELLAR trial.

The current gold standard for extraperitoneal locally advanced rectal cancer is total neoadjuvant therapy (TNT) followed by total mesorectal excision. This research explored the number of lymph nodes in patients with locally advanced rectal cancer after TNT and its correlation with survival. This is a post-hoc analysis based on the STELLAR trial, including patients with locally advanced rectal cancer from 16 tertiary centres who were randomized for short-term radiotherapy followed by chemotherapy (TNT group) or long-term concurrent chemotherapy group followed by total mesorectal excision between 2015 and 2018. This lymph node-related analysis is based on the TNT group. Subgroups were differentiated based on the lymph node harvest (below the median number: limited lymphadenectomy group, and greater than/equal to the median number: extended lymphadenectomy group). The primary outcomes were overall survival and disease-free survival (DFS). Correlations with clinical/pathological variables, lymphadenectomy categories and use of adjuvant chemotherapy were explored. Among the 451 patients enrolled in the STELLAR trial, 227 patients (50.3%) were assigned to the TNT group, including 29.5% females. The median number of lymph nodes retrieved in the TNT group was 11.0. Patients in the limited lymphadenectomy subgroup exhibited worse overall survival than those with extended lymphadenectomy (HR 2.95 (95% c.i. 1.47 to 5.92), P = 0.001). The overall survival was similar in the ypN0-limited and ypN1-extended subgroups (HR 0.38 (95% c.i. 0.11 to 1.30), P = 0.109). Adjuvant chemotherapy was associated with better overall survival and DFS than no adjuvant chemotherapy overall (P < 0.001) and in the limited lymphadenectomy subgroup (P < 0.001). However, there was no significant difference in overall survival or DFS with or without adjuvant chemotherapy in the extended lymphadenectomy subgroup (P = 0.887 and P = 0.192, respectively). In the STELLAR trial, the median number of lymph nodes harvested was 11. In patients with limited lymphadenectomy, the use of adjuvant therapy after TNT was beneficial and correlated with better prognosis compared with patients who did not receive adjuvant chemotherapy.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer

PurposeIn post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). MethodsLPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. ResultsAmong 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. ConclusionsLPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Outcome of Hypofractionated Radiotherapy for Localized Gastric Mucosa-associated Lymphoid Tissue Lymphoma.

With the prevalence of COVID-19, the importance of short-course radiotherapy (RT) in many cancers has been discussed. The aim of this study was to evaluate the results of hypofractionated schedule RT for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We assessed 45 patients with localized gastric MALT lymphoma who underwent RT between 2005 and 2019. The total RT dose ranged from 24-36 Gy in 10-18 fractions (median of 28 Gy/14 fractions). Patients were divided into three groups according to the dose fractionation: Group A, 30-36 Gy in 15-18 fractions; Group B, 26-28 Gy in 13-14 fractions; and Group C, 24-25 Gy in 10 fractions. All the patients achieved complete remission without local recurrence. The 5-year overall, cause-specific, and progression-free survival rates were 97.5%, 100%, and 97.5%, respectively, with a median follow-up period of 82 months. Among the dose fractionation groups, there were no statistically significant differences in local control or incidence of grade 2 or worse adverse events. Results of RT for localized gastric MALT lymphoma showed excellent local control and survival with no serious adverse events, regardless of dose fractionation. In situations where short-term RT is required, a hypofractionated RT schedule of 24-25 Gy in 10 fractions could be an option for RT schedules.

Immune infiltration could predict the efficacy of short-term radiotherapy in patients with cervical cancer.

Radiotherapyis the main treatment forcervical cancer. It is usually applied alone or in combination with surgery and/or chemotherapy. To explore the association between immune microenvironment of cervical cancer and radiotherapy response, we collected 20 paired cervical cancer tumor samples before and after radiotherapy and partial clinical information. With paired-end RNA-seq, we quantified the immune infiltration and tumor purity of these samples, and obtained 6350 differentially expressed genes before and after radiotherapy. With the help of R language, the function enrichment analysis and 22 immune cells infiltration analysis were carried out. Moreover, we built a random forest model based on the immune microenvironment to predict the short-term efficacy of radiotherapy. We found that the effect of radiotherapy on the immune microenvironment of stage III and IV cervical cancer patients was weaker than that of stage I and II cervical cancer patients. Radiotherapy can significantly reduce the tumor purity and increase immune infiltration. The proportions of the immune infiltrating cells are predictive of the radiotherapy efficacy. In addition, the local mucositis caused by radiotherapy can improve the curative effect of radiotherapy.

Clinical evaluation of toll-like receptor-5 agonist for radiation-induced oral mucositis in beagle dogs.

This study aimed to evaluate the clinical safety and validate the radiomitigative effect of KMRC011, against radiation-induced oral mucositis in beagle dogs. Clinical safety was evaluated by assessing tolerability, complete blood tests, and plasma biochemistry after drug administration. The radiomitigative effect of KMRC011 was evaluated macropathologically and histopathologically after inducing oral mucositis iatrogenically using 20 Gy irradiation. The plasma concentration of interleukin-6 was measured via enzyme-linked immunosorbent assay, as a biomarker of KMRC011 bioreactivity. Decreased tolerability, increased neutrophil count, hepatic enzyme concentration, C-reactive protein concentration, and interleukin-6 concentration after the administration was observed and ceased within 24 h without additional treatment. Although all animals included in the present study developed severe mucositis in the late course of the study, animals administered KMRC011 showed less erythema, ulcer, inflammatory infiltration. These results suggest that KMRC011 may be used as an adjuvant for radiotherapy without severe adverse effects, especially during short-term radiotherapy, such as hypofractionated radiotherapy or stereotactic radiotherapy.

Correlation between radiological and biological features and clinical outcomes in early prostate cancer: an exploratory subgroup analysis

PTEN deletion and Ki-67 expression are two of the most promising biomarkers in prostate cancer (PCa). In the same manner, multiparametric magnetic resonance imaging (mp-MRI) guided core biopsy is a powerful tool for PCa detection and staging. The aim of the study is to assess whether a correlation can be identified between the pathological stage defined by an mp-MRI-guided core biopsy and Ki-67 expression and PTEN deletion. Such correlation might be useful for staging and treatment personalization in PCa. This investigation was conducted in the context of phase II clinical study "Short-term radiotherapy for early prostate cancer with a concomitant boost to the dominant lesion" (AIRC IG-13218), ClinicalTrials.gov identifier: NCT01913717. Nineteen patients underwent a further in-bore MRI-targeted core biopsy (MRI-TBx) on the dominant intraprostatic lesion (DIL); on this basis, an additional Gleason Score (GS) was determined. PTEN loss and Ki-67 expression on these samples were analyzed and correlated with both risk categories modifications and oncological outcomes (overall survival, biochemical and clinical relapse). GS was upgraded in 5 cases, with 4 patients re-classified as intermediate-risk and 1 patient as high-risk. The latter experienced a clinical local relapse. No correlations between up/down-staging, PTEN deletion, and Ki-67 expression were observed in this cohort. Further investigations are needed towards the identification of a pattern in the tumor aggressiveness-response in PCa treated with ultra-hypofractionated radiotherapy. Moreover, a possible relationship between biomarker analysis and imaging textural features could be explored.

The impact of COVID-19 pandemic in the diagnosis and management of colorectal cancer patients.

The novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to healthcare systems worldwide, causing downscaling of almost all other activities, especially in its early stages. Currently, the availability of vaccines along with the spread of new viral variants has modified the epidemiology of the disease, and the previous activity is being gradually resumed in most healthcare facilities. In this review, we have summarized the influence of the COVID-19 pandemic in the diagnosis and management of colorectal cancer (CRC) patients. Population-based screening with either colonoscopy or fecal occult blood tests has proven to reduce CRC incidence and mortality, so screening programs have been implemented in most western countries. However, during the first COVID-19 wave, most of these programs had to be disrupted temporarily. In this review, we have thoroughly analyzed the consequences of these disruptions of screening programs as well as of the forced delays in diagnostic and therapeutic services on CRC prognosis, although its exact impact cannot be exactly measured yet. In any way, strategies to minimize its effect, such as catch-up strategies expanding the colonoscopy capacity or using fecal occult blood concentration and other risk factors to prioritize patients, are urgently needed. The COVID-19 pandemic has also led to a change in CRC patient presentation, with an overall temporary decreased incidence due to postponed diagnoses, but with more patients presenting in need of an emergency admission or with symptoms. Finally, changes in treatment approaches in CRC patients have been reported during the pandemic, namely a drop in the proportion of laparoscopic surgeries or a rise in short-term radiotherapy courses. We have therefore aimed to summarize the available evidence to guide the healthcare professionals treating CRC patients to choose the best treatment options in the current pandemic situation.

Identification of Autophagy Related circRNA-miRNA-mRNA-Subtypes Network With Radiotherapy Responses and Tumor Immune Microenvironment in Non-small Cell Lung Cancer.

Lung cancer (LC) is one of the most frequently diagnosed cancers and the leading cause of cancer death worldwide, and most LCs are non-small cell lung cancer (NSCLC). Radiotherapy is one of the most effective treatments for patients with lung cancer, either alone or in combination with other treatment methods. However, radiotherapy responses vary considerably among NSCLC patients. The efficacy of radiotherapy is influenced by several factors, among which autophagy is of importance. Autophagy is induced by radiotherapy and also influences cell responses to radiation. We explored the clinical significance of autophagy-related genes (ARGs) and gene sets (ARGSs) and the underlying mechanism in NSCLC patients treated with radiotherapy. First, differentially expressed ARGs (SNCA, SESN3, DAPL1, and ELAPOR1) and miRNAs (miR-205-5p, miR-26a-1-3p, miR-6510-3p, miR-194-3p, miR-215-5p, and miR-375-3p) were identified between radiotherapy-resistant and radiotherapy-sensitive groups. An autophagy-related radiosensitivity risk signature (ARRS) by nine ARmRNAs/miRNAs and an autophagy-related overall survival risk signature (AROS) by three ARmRNAs were then constructed with estimated AUCs of 0.8854 (95% CI: 0.8131–0.9576) and 0.7901 (95% CI: 0.7168–0.8685), respectively. The correlations between ARGSs or prognostic signatures and clinicopathological factors, short-term radiotherapy responses (radiotherapy sensitivity), long-term radiotherapy responses (overall survival), and immune characteristics were analyzed. Both ARGSs and prognostic signatures were related to immune checkpoint inhibitors (ICIs), infiltration of tumor-infiltrating immune cells (TIICs), and the activity of the cancer immune cycle. Finally, after target prediction and correlation analysis, circRNA (hsa_circ_0019709, hsa_circ_0081983, hsa_circ_0112354, hsa_circ_0040569, hsa_circ_0135500, and hsa_circ_0098966)-regulated miRNA/ARmRNA axes (miR-194-3p/SESN3, miR-205-5p/ELAPOR1, and miR-26a-1-3p/SNCA) were considered potential modulatory mechanisms by influencing the regulation of autophagy, macroautophagy, and chaperone-mediated autophagy.

A multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR): The final reports.

3510 Background: It’s presented the results of a phase III trial of short-term radiotherapy (SCRT) combined with chemotherapy versus long-term chemoradiotherapy (LCRT) in patients with locally advanced rectal cancer (LARC). Methods: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinomas diagnosed by MRI, were randomly assigned to experimental group or control group. In experimental group, patients received SCRT (25 Gy / 5 fractions / 5 days), followed by four courses of CAPOX. In control group, patients received LCRT (50 Gy / 25 fractions / 35 days with concurrent capecitabine). Surgery was recommended in both groups and performed 6-8 weeks after preoperative treatment. Two or six courses of CAPOX was prescribed as the postoperative chemotherapy in experimental group and control group, respectively. This trial was a multicenter, open-label, randomized, noninferior, phase III study, and all the patients were from 16 hospitals of China. The primary endpoint for this study was 3-year disease-free survival (DFS). Results: From Aug 30, 2015 to Aug 27, 2018, 599 patients were enrolled and entered random. Finally, 591 intention-to-treat (ITT) populations were included in the analysis, 298 patients assigned to SCRT followed by chemotherapy and 293 to CRT. For the experimental group and control group, cT3 and cT4 accounted for 82.3% vs. 84.6% and 15.4% vs. 12.3%, respectively, and approximately 85% were mrN positive (85.6% vs. 84.0%). As a whole, the completion and full-dose completion rates of preoperative treatment were 82.6% vs. 95.2% (p＜0.001) and 74.8% vs 93.2% (p＜0.001) in the experimental and control groups, respectively. Among the 465 patients who received surgery, 16.6% and 11.8% of them achieved pCR (p=0.134), respectively. Accounting for cCR after preoperative treatment, the total rate of pCR+cCR in experimental group was 22.5% and significantly higher than control group (12.6%, p=0.001). With median follow-up 35.0 months, the HR between experimental and control of DFS was 0.883, with 1-sided noninferiority p-value &lt;0.001, so the noninferiority hypothesis was confirmed. The probability of DFS and OS at 3 years was 64.5% and 86.5% in the experimental group compared with 62.3% and 75.1% in control group. It’s observed the OS rate of the experimental group was significantly higher than that of the control group (p=0.036) and no significant difference in metastasis-free survival or loco-regional recurrence was observed. Conclusions: For LARC with high risk factors, SCRT combined with sequential chemotherapy was noninferior to CRT and could be used as an alternative to LCRT. Meanwhile, SCRT combined with chemotherapy presented a higher cCR+pCR and 3-year overall survival rates as compared with CRT. However, the long term results need to be further followed up. (ClinicalTrails No.: NCT02533271 ). Clinical trial information: NCT00833131.

LncRNA linc00312 suppresses radiotherapy resistance by targeting DNA-PKcs and impairing DNA damage repair in nasopharyngeal carcinoma

Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients’ survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT–DNA–PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN–ATM–CHK2 signal and ATR–CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer.

BackgroundTumor-associated macrophages (TAM) constitute the most abundant immune cells in the tumor stroma initiating pro-inflammatory (M1) or immunosuppressive (M2) responses depending on their polarization status. Advances in tumor immunotherapy call for a detailed understanding of potential immunogenic mechanisms of irradiation routinely applied in rectal cancer patients.MethodsTo test the effects of radiotherapy on TAM, we ex vivo irradiated tissue samples of human rectal cancer and assessed the phenotype by flow cytometry. We furthermore evaluated the distribution of leucocyte subsets in tissue sections of patients after short-course radiotherapy and compared findings to non-pretreated rectal cancer using an immunostaining approach. Organotypic assays (OTA) consisting of macrophages, cancer-associated fibroblast and cancer cell lines were used to dissect the immunological consequences of irradiation in macrophages.ResultsWe demonstrate that short-course neoadjuvant radiotherapy in rectal cancer patients is associated with a shift in the polarization of TAM towards an M1-like pro-inflammatory phenotype. In addition, ex vivo irradiation caused an increase in the phagocytic activity and enhanced expression of markers associated with stimulatory signals necessary for T-cell activation. In OTA we observed that this alteration in macrophage polarization could be mediated by extracellular vesicles (EV) derived from irradiated tumor cells. We identified high mobility group box 1 in EV from irradiated tumor cells as a potential effector signal in that crosstalk.ConclusionsOur findings highlight macrophages as potential effector cells upon irradiation in rectal cancer by diminishing their immunosuppressive phenotype and activate pro-inflammation. Our data indicate that clinically applied short-term radiotherapy for rectal cancer may be exploited to stimulate immunogenic macrophages and suggest to target the polarization status of macrophages to enhance future immunotherapeutic strategies.

Long-lasting Thrombocytopenia after Transient Pancytopenia Induced by Short-Term Concomitant Radiotherapy and Temozolomide.

Some patients may experience severe haematological manifestations after even short-term radiotherapy with temozolomide.In everyday practice, clinical models precisely predicting the haematological toxicity of concomitant treatment with temozolomide and radiotherapy is necessary, especially in countries where genetic tests are not available.Incomplete recovery of the cells of a particular bloodline over a long period may necessitate permanent discontinuation of chemotherapy or radiotherapy.

496P - Short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR): A planned interim analysis

496P - Short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR): A planned interim analysis

Efficacy characteristics of different therapeutic modalities for locally advanced prostate cancer: a Bayesian network meta-analysis of randomized controlled trials.

Though previous studies have investigated the efficacy characteristics of several different therapeutic modalities for locally advanced prostate cancer (LAPCa) patients, the available results remained unestablished. Therefore, the aim of this meta-analysis was conducted to clarify such differences. The online PubMed, EMBASE and Web of Science were comprehensively searched for relevant studies published before September 1st, 2017, and eventually eleven relevant studies met the inclusion criteria. The hazard odds ratios (HRs) with 95% credible interval (CI) were utilized to evaluate the efficacy characteristics of several different therapeutic modalities for LAPCa patients by Markov chain Monte Carlo methods. Five different therapeutic modalities were ultimately enrolled to shed light on the efficacy characteristics for LAPCa patients and seven different clinical outcomes were finally analyzed in this study. The cumulative rank probability of overall survival (OS) or cancer-specific survival (CSS) from best to worst was radiotherapy (RT) + orchiectomy, RT + long-term androgen deprivation therapy (LTADT), RT + short-term androgen deprivation therapy (STADT), LTADT and RT; RT + LTADT, RT + orchiectomy, RT + STADT, LTADT and RT, respectively. Meanwhile, in the terms of progression-free survival (PFS), biochemical failure rate (BFR), disease-free survival (DFS), local progression rate (LPR) and metastasis rate (MR), RT + LTADT as well as RT + STADT had a higher, whereas RT alone or LTADT had a relatively lower treatment effect. All in all, our results indicated that RT + LTADT or RT + orchiectomy was among the best two therapeutic regimens in the prognostic aspects of the patients with LAPCa. Furthermore, in consideration of reducing invasive treatment of eligible patients, RT + LTADT could yield better survival benefit of LAPCa patients, compared with others. In addition, the results of our analysis might provide a reference in the clinical selection. Larger sample sizes of strictly designed randomised controlled trials (RCTs) were wanted to validate our findings.

The gentamicin-collagen implant and the risk of distant metastases of rectal cancer following short-course radiotherapy and curative resection: the long-term outcomes of a randomized study

PurposeA previous randomized study conducted by our group showed that application of gentamicin-collagen implant (GCI) into the pelvic cavity after total mesorectal excision (TME) reduced the incidence of distant metastases. Therefore, we decided to conduct a confirmatory study.MethodsPatients with rectal cancer were included in the study if they met the following criteria: adenocarcinoma of the rectum, preoperative short-term radiotherapy (5 × 5 Gy), and WHO performance score 0–1.ResultsOne hundred seventy-six patients were randomly assigned either to an experimental group in which GCI was applied (n = 81) or to a control group without GCI (n = 81). Median follow-up was 80 months. Cumulative incidence of distant metastases at 5 years was higher in the control group compared to the experimental group: 23.5 vs 8.6% (HR 2.4 [95% CI 1.1–5.5], P = 0.005). Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) did not differ between the experimental group and the control group: HR 0.95 [95% CI 0.55–1.70], P = 0.864; HR 0.85 [95% CI 0.50–1.45], P = 0.548, and HR 0.5 [95%CI 0.22–1.22], P = 0.093, respectively. The predefined by the protocol subgroup analysis for yp stage III disease showed better DFS in the experimental group compared to the control group; HR 0.47 [95%CI 0.23–0.97], P = 0.042).ConclusionsThe results confirmed our previous finding that GCI applied in the pelvis significantly reduced the rate of distant metastases in patients after radical rectal cancer resection.

Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma

The optimal treatment for patients with glioblastoma with unfavorable prognostic factors, such as old age and low performance status, remains controversial. We conducted a prospective study to assess the effect of temozolomide and short-course radiation versus short-course radiation alone in the treatment of poor-prognosis patients with newly diagnosed glioblastoma. Forty-five patients with a newly diagnosed glioblastoma, older than 70 years or aged 50-70 years and with a Karnofsky performance score <or=70 were enrolled in this prospective study. Twenty-three patients were treated with an abbreviated course of radiotherapy (30 Gy in 6 fractions over 2 weeks) and 22 patients with the same radiotherapy schedule plus adjuvant temozolomide at the dose of 150-200 mg/m(2) for 5 days every 28-day cycle. The primary end point was overall survival. Secondary end points included progression-free survival and toxicity. Median overall survival was 7.3 months in the radiotherapy group and 9.4 months in the radiotherapy plus temozolomide group (P = 0.003), with respective 6-month overall survivals of 78% and 95%, respectively. Median progression-free survival was 4.4 months in the radiotherapy group and 5.5 months in the radiotherapy plus temozolomide group (P = 0.01), and respective 6-month progression-free survival rates were 22% and 45%. In multivariate analysis, Karnofsky performance score was the only significant independent predictive factor of survival (P = 0.03). Adverse effects of radiotherapy were mainly represented by neurotoxicity (24%), which resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 36% of patients treated with temozolomide. The addition of temozolomide to short-term radiotherapy resulted in a statistically significant survival benefit with minimal additional toxicity in poor-prognosis patients with newly diagnosed glioblastoma. Future studies need to define the best combined regimens of radiotherapy and temozolomide on survival and quality of life in this subgroup of patients.

MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer.

Matrix metalloproteinase 7 (MMP7) expression is highly associated with colorectal cancer and modulates tumour growth and invasion. Radiation injury induces inflammation with increases in MMP7 and in transforming growth factor beta (TGFβ). The aim of this study was to investigate the effect on MMP7 and TGFβ. expression in patients with rectal cancer undergoing different regimens of neoadjuvant radiotherapy (RT). We studied 53 patients in three RT treatment groups receiving RT of 25 Gy, long-term RT 50 Gy and controls receiving no RT. Three biopsies were obtained from each patient during the treatments: before RT, after RT and after surgery. Tissue samples were formalin fixed, paraffin embedded and tissue microarrays were constructed and stained for MMP7 and TGFβ. Mann-Whitney U-tests and Wilcoxon Z-tests were used to determine differences between patients before and after RT, and after surgery, as well as between the RT groups. In all three patient groups, increases of MMP7 and TGFβ expression were observed after surgery. MMP7 expression was significantly increased in patients receiving short-term RT but TGFβ expression was not affected by RT. 50 Gy Irradiation of rectal cancer gives less tumour activation of MMP7, whilst it is up-regulated by 25 Gy and surgery regardless of RT.

Longer-Term Androgen Deprivation Therapy Improves Cancer-Specific Survival in Patients With Gleason Score 9-10 Prostate Adenocarcinoma: An Individual Patient-Level Meta-analysis of RTOG 8531, 8610, and 9202

It has been suggested that Gleason grade 5 prostate carcinoma (PCa) is less responsive to androgen deprivation therapy (ADT) than lower grade PCa. Three randomized trials—RTOG 8531, 8610, and 9202—have examined the effect of ADT utilization and duration when used in concert with definitive radiotherapy (RT). The purpose of this study was to evaluate the effect of ADT on clinical outcomes of patients with Gleason score (GS) 9-10 PCa, who by definition had Gleason grade 5-containing PCa. Patients enrolled in RTOG 8531 were randomized to lifelong ADT vs. RT alone, those in RTOG 8610 to short-term ADT (STADT, 4 mos) vs. RT alone, and those in RTOG 9202 to long-term ADT (LTADT, 28 mos) vs. STADT. Data was obtained from the NRG via a data sharing agreement to allow for analysis of a total of 351 patients enrolled on these protocols who had GS 9-10 PCa. For overall survival (OS) and distant metastasis-free survival (DMFS), patient-level data were used to obtain hazard ratio (HR) and standard error estimates of pair-wise treatment effects after fitting multivariate Cox proportional hazards models adjusting for age, GS (9 or 10) and T-stage. For cancer-specific survival (CSS), HRs were obtained by fitting cause-specific competing risk models to the data. A Network Meta-Analysis (NMA) approach was adopted for pair-wise meta-analysis of all pairs of treatments. Along with analyzing within-trial comparisons between two treatments, the NMA framework enables incorporation of indirect comparisons constructed from two trials that have one treatment in common. The median follow-up was 6.01 years. Overall, lifelong ADT was associated with significantly improved DMFS, CSS, and OS when compared with RT alone and STADT; only DMFS was improved with lifelong ADT versus LTADT (Table 1). LTADT offered significantly higher DMFS than STADT ADT, but not RT alone. Though not statistically significant, the HRs for STADT vs. RT alone were in the direction of an inferior effect on all three outcomes.Abstract 287; Table 1Results of Network Meta-AnalysisDMFSCSSOSRT Alone As ReferenceSTADT1.27 (.71, 2.26)1.22 (0.64, 2.35)1.52 (0.7, 2.66)LTADT0.88 (0.45, 1.72)0.68 (0.28, 1.64)1.18 (0.61, 2.28)Lifelong ADT0.37 (0.24, 0.57)**0.34 (0.18, 0.61)**0.56 (0.37, 0.85) **STADT as ReferenceLTADT0.69 (0.49, 0.98)**0.56 (0.31, 1.00)0.77 (0.54, 1.110)Lifelong ADT0.29 (0.14, 0.60)**0.27 (0.11, 0.67)**0.37 (0.18, 0.74)**LTADT as ReferenceLifelong ADT2.38 (1.07, 5.30)**2.03 (0.70, 5.88)2.10 (0.96, 4.58)**P<0.05. Open table in a new tab **P<0.05. GS 9-10 PCa appear to show a temporal dose-response to ADT, contrary to the hypothesis that grade 5 cancers are relatively hormone-insensitive. The inferior outcomes with STADT are likely the result of a small sample size. The extension of these findings in the modern era of dose-escalated radiotherapy constitutes an area of future study.

Results of Short Term Radiotherapy Followed by Radical Surgery for Rectal Cancer: A Long-Term Unicenter Observational Study

IntroductionShort-term radiotherapy (STR) for rectal cancer (RC) has rarely been used in Spain. The aim of the present study is to describe oncological results after RTC and surgery for RC. MethodsThis is a retrospective analysis of a consecutive series of patients treated with STR and surgery for RC (1999–2012). Epidemiological data, staging, complications of STR, STR-surgery interval, surgical approach, rate of anastomotic/perineal wound dehiscence, and pathological data (regression degree and staging) were collected. Global survival, disease free survival, local recurrence rate and incidence of toxicity, response and complications of combined treatment are reported. ResultsOf 1229 patients treated, 209 patients received STR and surgery. The median follow-up was 6.2 years. Mean age was 68 years and 66% of the patients were men. A total of 88% were cT3-4 and 44% cN+17 (8.1%) patients had resectable synchronous metastases. Acute and chronic toxicity due to STR was <5%. In 75% of the cases the STR-surgery interval was <15 days, and in 9% >4 weeks. Seven patients (3.3%) presented complete response. Nine (4.3%) patients presented a local recurrence rate. Global survival at 5, 10 and 15 years was 67.8%, 49.2% and 37.5%, respectively. Disease free survival at 5, 10 and 15 years was 66.1%, 47.1% and 33%, respectively. ConclusionsThe results compare favorably with multicentric historical series. STR offers certain advantages that could be increased by increasing the STR-surgery interval and/or interspersed with sequential chemotherapy.

Combined abiraterone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP.

45 Background: Salvage radiotherapy (RT) plus 6 months LH-RH therapy (ADT) improves biochemical relapse free survival in men with rising PSA following prostatectomy. Abiraterone acetate (Aa) increases overall survival in metastatic prostate cancer. We aimed to establish the toxicity of adding Aa combined with salvage RT and 6 months goserilin (Gos). Methods: We enrolled pT2-pT4a pN0 prostate cancer patients (pts) with rising PSA (0.2 to &lt;2.0 μg/l) following radical prostatectomy. The primary endpoint was to determine the Maximum Tolerated Dose and recommended dose of Aa during RT plus Gos, two dose levels tested : 1 (750mg) and 2 (1000 mg). Two different schemes were explored: Sheme A: Aa (1000 mg) and predisone (10 mg) were given orally during 1 month to salvage IMRT (66 Gy in 33 fractions). The first day of irradiation, Aa is reduced to level 1 or 2 and 10.8 mg Gos is injected (sc). In sheme B, Gos is injected the first day (1 month before starting RT). Results: We recruited 9 + 9 pts in scheme A and B respectively. In scheme A, Testosterone (Tst) levels declined to castration level (&lt;0.5ng/ml) after 10 days . Two/9 pts did not achieve castration levels at 30 days. Median LH levels increased to 10.4 (D10) and 12.5 IU/l (D20). At dose level 1, 4/9 pts (44%) experienced grade 3 hepatitis, occurring prior to RT or during RT (8 Gy, 36 and 54 Gy). We hypothesized that this unexpected liver toxicity was related to the LH increase during the first month (Aa administration without Gos). Therefore, we modified LH-RH administration (scheme B) and recruited 9 more pts. Tst levels dropped to undetectable at day 6, while median LH levels decreased to 6.1 (D10) and 1.7 IU/l (D20). At dose level 1 (3 + 3 pts), no grade 3 liver toxicity was reported. No other grade 3 toxicity was recorded. At dose level 2, 2/3 pts had grade 3 hepatitis occurring during RT. CYP17 polymorphism did not correlate with liver toxicity. Conclusions: The recommended dose of Aa combined to short-term androgen deprivation and salvage RT is 750 mg. Aa alone did lead to castration levels in 22% of pts.An unexpected high frequency of grade 3 liver toxicity was observed. Clinical trial information: NCT01780220.