Effect Of Postoperative Radiotherapy Research Articles

Impact of radiation therapy for breast cancer with involved surgical margin after immediate breast reconstruction: A multi-institutional observational study

IntroductionInvolved surgical margins are risk factors for local recurrence and re-excision is often difficult, particularly in patients with breast cancer undergoing immediate breast reconstruction (IBR). However, the magnitude of the effect of radiation therapy on preventing local recurrence for breast cancers with involved margins has not been sufficiently assessed. Materials and methodsWe retrospectively assessed sites of involved surgical margins and local recurrence after mastectomy with IBR in patients with early breast cancer between 2008 and 2016. The effect of postoperative radiation therapy was evaluated in patients with involved margins, adjusted for nuclear grade, lymphatic invasion, surgical procedures, and primary systemic therapy. ResultsA total of 274 (5.8 %) out of 4726 patients who underwent mastectomy with IBR had involved surgical margins: 133, 68, 88, and 26 had involvement of the skin, deep margin, lateral margins, and nipple, respectively (including duplicates). Radiation therapy was administered to 54 patients with involved margins. In patients with involved margins, 7-year cumulative incidences of local recurrence were 1.9 % and 12.6 % with and without radiation therapy, respectively (adjusted hazard ratio, 0.17; 95 % CI, 0.04–0.80). Local recurrence occurred in 28 patients, and the sites were skin, subcutaneous tissue, muscle, and nipple-areola complex in 7, 17, 1, and 3 patients, respectively. Among them, 23 (82.1 %) were associated with involved margin sites. ConclusionsRadiation therapy meaningfully reduced the incidence of local recurrence in patients with breast cancer with margin involvement after mastectomy with IBR. Most local recurrences occurred at involved margin-related sites.

The high-risk features and effect of postoperative radiotherapy on survival for patients with surgically treated stage IIIA-N2 non-small cell lung cancer

ObjectivesAlthough postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC.Materials and methodsThis study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan–Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability.ResultsOf all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85–0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93–1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85–1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94–1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98–1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99–1.23, P = 0.07).ConclusionPORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

Effect of postoperative radiotherapy on survival in patients with completely resected and pathologically confirmed stage N2 non-small-cell lung cancer: a systematic review and meta-analysis.

The role of postoperative radiotherapy (PORT) for patients with completely resected stage N2 non-small-cell lung cancer (NSCLC) has been controversial. This study aimed to investigate the efficacy of PORT and prognosis in these patients. An updated meta-analysis was conducted in this study to investigate the efficacy of PORT and prognosis in patients with completely resected and pathologically confirmed stage N2 NSCLC. This study is a systematic review and meta-analysis. Databases were searched up to 2 March 2022. All trials on patients with completely resected and pathologically confirmed stage N2 NSCLC undergoing PORT were screened, and data indicators in the PORT and non-PORT groups were extracted, respectively. The effect of PORT on overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) was estimated. Subgroup and sensitivity analyses were performed. In all, 20 studies involving 6340 patients were finally included. The PORT significantly increased OS [hazard ratio (HR) = 0.77, 95% CI: 0.71-0.84, p < 0.001), LRFS (HR = 0.63, 95% CI: 0.52-0.76, p < 0.001), and DFS (HR = 0.72, 95% CI: 0.63-0.82, p < 0.001) while it showed no significant difference in improving DMFS (HR = 0.86, 95% CI: 0.71-1.05, p = 0.14). Our results suggest that in the postoperative treatment of patients with completely resected and pathologically confirmed stage N2 NSCLC, the addition of PORT provides better local recurrence control and survival benefit, but no benefit for distant metastases. The PORT may be incorporated into the postoperative treatment options for some patients with high-risk factors. However, it needs to be validated by more prospective studies in the future. CRD42022314095.

Effects of postoperative radiotherapy and docetaxel and PD-1 inhibitors on the survival and safety of glioblastoma patients: a systematic review and meta-analysis.

The present standard treatment rarely allows the complete removal of glioblastoma (GBM). So postoperative treatments are provided to prevent or delay tumor recurrence. The overall survival (OS) rate and safety of postoperative chemotherapy alone, or combined with radiotherapy (RT), or programmed cell death-1 (PD-1) inhibitor in GBM is still unclear. The present goal was to explore postoperative treatment's effect on the survival and safety of patients with GBM. We searched the mainstream online databases for clinical studies of RT and chemotherapy and PD-1 inhibitors in the treatment of GBM published up to May 2020. The patients in the experimental group accepted an anti-PD-1 drug alone and RT + chemotherapy, whereas the controlled patients were treated with docetaxel alone. The literature qualities were assessed using Cochrane Risk of Bias 2.0, and studies were assigned. The meta-analysis was conducted by RevMan 5.4 software. A total of 927 articles were identified through the online database search. The articles unable to meet the inclusion criteria were excluded leaving 6 studies for inclusion in the study. Compared with docetaxel-based chemotherapy for GBM, combined RT chemotherapy and PD-1 inhibitor therapy had better OS [mean difference (MD), -1.75; 95% confidence interval (CI): -2.99 to -0.51; P=0.006] and progression-free survival (PFS) and a lower incidence of adverse reactions (MD, -7.03; 95% CI: -7.64 to -6.42; P<0.00001) above grade III. Postoperative combination of RT and chemotherapy and PD-1 inhibitors had some advantages over docetaxel in terms of effectiveness. More clinical trials are needed to confirm effectiveness.

The Prognostic Value of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma: A Propensity-Matched Study Based on SEER Database.

Simple SummaryAlthough surgery has been recognized as the cornerstone of treatment for patients with resectable thymic epithelial tumors, the role of postoperative radiotherapy remains controversial. We performed this SEER-based propensity-matched analysis to investigate the prognostic value of postoperative radiotherapy in thymoma and thymic carcinoma. The results showed that postoperative radiotherapy improved both overall survival and cancer-specific survival in patients with Masaoka-Koga stage IIB–IV thymoma. This study is the first to demonstrate the prognostic value of postoperative radiotherapy in stage IIB thymic carcinoma. This large, up-to-date population-based longitudinal study may provide guidance on the use of postoperative radiotherapy for a thymoma or thymic carcinoma.(1) Objectives: The effect of postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. This study aimed to investigate the prognostic value of PORT for thymoma and thymic carcinoma in a population-based registry. (2) Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with thymoma and thymic carcinoma between 2010 and 2019. Propensity score matching was performed to adjust statistical influences between the PORT and non-PORT groups. (3) Results: A total of 2558 patients with thymoma (n = 2138) or thymic carcinoma (n = 420) were included. In the multivariate analysis, PORT was an independent prognostic factor for OS (overall survival; p < 0.001) and CSS (cancer-specific survival; p = 0.001) in thymoma and an independent prognostic factor for OS in thymic carcinoma (p = 0.018). Subgroup analyses revealed that PORT was beneficial to OS and CSS in patients with Masaoka-Koga stage IIB-IV thymoma (OS: IIB, p < 0.001; III-IV, p = 0.005; CSS: IIB, p = 0.015; III-IV, p = 0.002) and stage IIB thymic carcinoma (OS: p = 0.012; CSS: p = 0.029). (4) Conclusion: This propensity-matched analysis identified the prognostic value of PORT in thymoma and thymic carcinoma based on the SEER database. For patients with stage IIB-IV thymoma and stage IIB thymic carcinoma, PORT was associated with improved OS and CSS. A more positive attitude towards the use of PORT for nonlocalized thymoma and thymic carcinoma may be appropriate.

Effect of postoperative radiotherapy in women with localized pure mucinous breast cancer after lumpectomy: a population-based study

PurposePure mucinous breast cancer is a rare subtype of invasive breast cancer with favorable prognosis, in which the effect of postoperative radiotherapy remains unclear. We aimed to investigate the prognostic value of postoperative radiotherapy in women with localized pure mucinous breast cancer after lumpectomy.MethodsWe conducted a retrospective cohort study to compare the effectiveness of postoperative radiotherapy (RT) and omitting postoperative radiotherapy (non-RT) in patients with first primary T1-2N0M0 (T ≤ 3 cm) pure mucinous breast cancer who underwent lumpectomy between 1998 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database. Breast cancer-specific survival (BCSS) was compared between RT and non-RT groups using Kaplan–Meier method and Cox proportional hazards regression model. Propensity score matching (PSM) was carried out to balance cohort baselines. In addition, an exploratory analysis was performed to verify the effectiveness of RT in subgroup patients.ResultsOf 7832 eligible patients, 5352 (68.3%) underwent lumpectomy with postoperative RT, 2480 (31.7%) received lumpectomy without postoperative RT. The median follow-up duration was 92 months. The median age was 66 years in the RT group and 76 years in the non-RT group.The 15-year BCSS was 94.39% (95% CI, 93.08% to 95.35%) in the RT group versus 91.45%(95% CI, 88.93% to 93.42%) in the non-RT group (P < 0.001). The adjusted hazard ratio for BCSS was 0.64 (95% CI, 0.49 to 0.83; P = 0.001) for RT group versus non-RT group. After propensity score matching, similar results were yielded. Adjuvant RT reduced the 15-year risk of breast cancer death from 7.92% to 6.15% (P = 0.039). The adjusted hazard ratio for BCSS were 0.66 (95%CI, 0.47 to 0.92; P = 0.014) for RT group versus non-RT group. The benefit of RT was well consistent across subgroup patients.ConclusionAmong women with T1-2N0M0 (tumor size ≤ 3 cm) pure mucinous breast cancer, the addition of RT after lumpectomy was significantly associated with a reduced incidence of breast cancer death compared with non-RT, and the magnitude of benefit may be modest. This suggests that postoperative RT is recommended in the treatment of localized pure mucinous breast cancer.

Risk factors for wound-related complications after surgical stabilization of spinal metastases with a special focus on the effect of postoperative radiation therapy

BackgroundAdvancements in the field of oncological therapies during the last decades have led to a significantly prolonged survival of cancer patients. This has led to an increase in the incidence of spinal metastases. The purpose of this study was to assess risk factors for wound-related complications after surgical stabilization of spinal metastases with a special focus on the effect of postoperative RT and its timing.MethodsPatients who had been treated for metastatic spine disease by surgical stabilization followed by radiotherapy between 01/2012 and 03/2019 were included and a retrospective chart review was performed.ResultsOf 604 patients who underwent stabilizing surgery for spinal metastases, 237 patients (mean age 66 years, SD 11) with a mean follow-up of 11 months (SD 7) were eligible for further analysis. Forty-one patients (17.3%) had wound-related complications, 32 of them before and 9 after beginning of the RT. Revision surgery was necessary in 26 patients (11.0%). Body weight (p = 0.021), obesity (p = 0.018), ASA > 2 (p = 0.001), and start of radiation therapy within 21 days after surgery (p = 0.047) were associated with an increased risk for wound complications. Patients with chemotherapy within 3 weeks of surgery (12%) were more likely to have a wound-related surgical revision (p = 0.031).ConclusionBody weight, obesity and ASA > 2 were associated with an increased risk for wound complications. Patients with chemotherapy within 3 weeks of the surgery were more likely to have a wound-related revision surgery. Patients who had begun radiation therapy within 21 days after surgery were more likely to have a wound complication compared to patients who waited longer.

Effects of postoperative radiotherapy on cardiovascular-pulmonary disease mortality in patients with stage IIIA-N2 resected NSCLC: analysis of the SEER database

BackgroundThe role of postoperative radiotherapy (PORT) in cardiovascular-pulmonary disease mortality in patients with stage IIIA-N2 resected non-small cell lung cancer (NSCLC) remains uncertain. The purpose of this population-based analysis was to explore the effect of PORT on cardiovascular-pulmonary disease mortality in these patients.MethodsPatients aged ≥ 18 years with stage IIIA-N2 resected NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and were grouped according to the use of PORT. Propensity score matching (PSM) was used to account for differences in baseline characteristics between the Non-PORT and PORT groups. The cumulative risk for cardiovascular-pulmonary disease death was estimated using the cumulative incidence curve. Competing risk regression was used to run univariate and multivariate analyses to evaluate risk factors.ResultsA total of 3981 patients were included in the study population. Among them, 1446 patients received PORT, and 2535 did not. A total of 1380 patients remained in each group after PSM, and the baseline characteristics were not significantly different between the two groups. The cumulative incidence of cardiovascular-pulmonary mortality was 10.93% in the Non-PORT group compared with 9.85% in the PORT group. There was no significant difference in the cumulative risk between the two groups (HR 1.07, 95% CI 0.77–1.48, p = 0.703). Multivariate analysis indicated that PORT had no significant impact on increased risk, with an HR of 1.18 (p = 0.377).ConclusionsNo significant differences between the PORT and Non-PORT groups were found in cardiovascular-pulmonary-specific modalities in this study. Further studies are required to validate these results. This study highlights the importance of long-term surveillance for NSCLC patients.

Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02).

PurposeThis study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.Materials and MethodsThis study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.ResultsThe median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3.ConclusionPORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

Postoperative radiotherapy is associated with improved survival in pT1-2N1 oral and oropharyngeal cancer\xa0without adequate neck dissection

BackgroundTo assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.MethodsIn the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection.ResultsOf the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49–0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19–24 LNs removed (aHR 0.78; 95% CI 0.73–1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75–1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45–0.97) in those with < 18 LNs. The protective effect was not seen in those with 18–24 LNs (aHR 1.07; 95% CI 0.59–1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81–1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed.ConclusionRadiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.

Effect of Postoperative Radiotherapy in Thymoma Patients: A SEER-Based Study

Introduction: The role of postoperative radiation therapy (PORT) for thymoma is under debate, especially in patients aged ≥60 years with an advanced stage (Masaoka stages III and IV). We aimed to evaluate the efficacy of PORT for thymoma in a population-based registry. Methods: A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to compare the outcomes of thymoma patients with or without PORT. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Conditional inference tree analyses were performed for risk classification according to the study variables. Cox regression was performed to evaluate the prognostic effect of PORT in the specific subgroups. Results: A total of 2,236 patients were included. The conditional inference tree analysis identified that an age ≥60, a Masaoka stage ≥3, and the year of diagnosis were important factors when classifying patients into prognostic subgroups. PORT was found to be a protective predictor of OS in patients aged ≥60 years, those with a Masaoka stage III—IV, and those diagnosed after 2005. Further subgroup analyses revealed that PORT was significantly associated with a better OS (HR = 0.77) in patients aged ≥60 years, whereas it was not significantly associated with CSS. Conclusions: An older age (≥60 years) is critical for predicting survival outcomes in thymoma patients. Moreover, patients aged ≥60 years could benefit from PORT in terms of OS.

Effects of Postoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non-Small Cell Lung Cancer: Analysis of the SEER Database.

The role of postoperative radiotherapy (PORT) in patients with resected stage IIIA non-small cell lung cancer (NSCLC) remains controversial. The purpose of this study was to explore the effect of PORT on survival of these patients. Patients aged ≥18 years with stage IIIA NSCLC were identified in the SEER database from 2010 through 2015. Cox regression analysis was used to identify independant prognostic factors in patients with stage IIIA NSCLC. Subgroup analysis of patients stratified by N stage was also performed. Overall survival and lung cancer-related death were compared among the different groups by using Kaplan-Meier analysis and competitive risk analysis. A total of 5,168 patients (1,711 of whom received PORT) were included in the study. In multivariable analysis, PORT was an independent prognostic risk factor for patients with N1 stage (hazard ratio [HR], 1.416, 95% CI, 1.144-1.753; P=.001). PORT was a favorable prognostic factor for patients with stage IIIA, N2 disease with ≥6 positive lymph nodes (HR, 0.742; 95% CI, 0.587-0.938; P=.012). Median survival time of patients with stage IIIA, N2 disease with ≥6 positive lymph nodes who received postoperative chemotherapy combined with PORT was significantly longer compared with those who received postoperative chemotherapy alone (32 vs 25 months, respectively; P=.009). The competitive risk model revealed that 3- and 5-year lung cancer-related mortality rates increased by 8.99% and 16.92%, respectively, in patients with N1 disease who were treated with PORT, whereas the 3-year mortality rate decreased by 4.67% and the 5-year mortality rate by 10.08% in patients with N2 disease and ≥6 positive lymph nodes who were treated using PORT. Our results revealed that PORT significantly improved overall survival and decreased lung cancer-related mortality in patients with stage IIIA, N2 disease with ≥6 positive lymph node metastases. PORT was not recommended for patients with N0 and N1 disease.

Analysis of the prognostic factors of triple-negative breast cancer and the clinical efficacy of postoperative radiotherapy in early cases.

e12502 Background: To explore the prognostic value of pretherapeutic peripheral blood parameters and breast imaging-reporting and data system (BI-RADS) classification of triple-negative breast cancer (TNBC) and the effect of postoperative radiotherapy in early cases. Methods: A total of 278 TNBC patients’ medical records between January 2013 and December 2018 were retrospectively collected, including white blood cells, neutrophils, lymphocytes, platelets, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum tumor markers, BI-RADS classification, TNM staging and therapeutic methods. We used the log-rank test and Kaplan-Meier curves to assess the progression-free survival (PFS) of enrolled patients. Multivariate prognostic analysis was performed by the Cox regression model. Results: The median PFS of all 278 patients was 20 months (4-72 months) at the end of follow-up. Operable patients who obtained adjuvant chemotherapy had a better median PFS (20 vs 18.5 months, P= 0.018, HR = 5.943, 95% CI: 1.36-25.92) than those without. Lymph node metastasis (52%) and chest well relapse (28%) were the critical failure forms followed by other metastases (12% lungs, 9.3% bones, 4% liver and 2.7% brain) with p value less than 0.001. Multivariate analysis indicated that platelet counts &gt; 113.5×109/L (p = 0.024), PLR ≤ 111.7 (p = 0.036) and CA15-3 ≤ 8.4 U/mL (p = 0.003) were significantly associated with the favourable prognosis of PFS in TNBC patients. Furthermore, BI-RADS of grade 2-4 had a better median PFS compared with grade of 5-6(20 vs 17.5 months, p = 0.008, HR = 2.154, 95% CI: 1.219-3.805). In subgroup analysis, forty-three early cases with pN1 stage earned additional benefits from postoperative radiotherapy in terms of low risk of distant metastasis and recurrence (p = 0.014). Residual tumor after surgery was another important factor of poor prognosis (p = 0.029). Conclusions: Adjuvant chemotherapy improved median PFS for operable TNBC patients and pretherapeutic platelets, PLR, CA15-3 and BI-RADS were the independent prognostic factors of survival. Lymph node metastasis and chest well relapse were the main patterns of treatment failure. Radiotherapy could reduce the risk of disease progression for postoperative patients with N1 stage.

DNA repair gene expression is associated with differential prognosis between HPV16 and HPV18 positive cervical cancer patients following radiation therapy

Cervical cancers are almost always induced by HPV infections, of which HPV16 and HPV18 are predominant. Cancers associated with these strains are induced through DNA repair factors and have a differential response to radiation therapy. Hence this study focuses on finding DNA repair gene expression differences in HPV16 and HPV18 positive cervical cancers after radiation therapy. A higher number of somatic mutations were observed in HPV16 positive cervical tumours for patients that were disease free when compared to those who recurred/progressed. Moreover, hierarchal clustering of RNAseq data from The Cancer Genome Atlas was conducted to identify groups of DNA repair genes associated with a differential prognosis for cervical cancer following postoperative radiation therapy. TP53BP1, MCM9 (at higher than mean levels), POLR2F and SIRT6 (at lower than mean levels), were associated with an increase in patients experiencing cervical cancer recurrence/progression following postoperative radiation therapy when HPV18 positive, but not HPV16 positive. The expression patterns of these genes provide an explanation for the higher rate of postoperative radiation therapy resistance associated with HPV18 positive cervical cancer patients. Therefore, HPV18 positive cervical tumours may be more likely retain a greater non-homologous end joining and homologous recombination pathway activity, which could dampen the effect of postoperative radiation therapy. Moreover, greater susceptibility to postoperative radiation therapy could be caused by the reliance of cervical cancer cells upon the single-strand annealing and nucleotide excision pathways for repair of DNA damage.

Abstract PD6-10: A high ratio of CD8/FOXP3 predicts an unfavorable response to postoperative radiotherapy after breast-conserving surgery: Results from the randomized SweBCG91RT trial

Abstract Purpose: The effect of postoperative radiotherapy (RT) based on the immune phenotype of tumor-infiltrating lymphocytes (TILs) has not been investigated. The purpose of this study was to analyze how the balance between CD8+ T cells and T regulatory cells (FOXP3+), which have opposite effects on the anti-tumoral defense, affects the risk of ipsilateral breast tumor recurrence (IBTR) and of any recurrence as well as the interaction with RT in a large randomized RT trial. Methods: In the SweBCG91RT trial, patients with breast cancer stage I and II were randomized to breast conserving surgery (BCS) and postoperative RT or BCS only and followed for a median time of 15.2 years. Tumor blocks were retrieved and stromal TILs were assessed through hematoxylin-eosin stained slides. CD8+ T cells and T regulatory cells were evaluated through staining for CD8 and FOXP3 and the percentage of stroma occupied by CD8+ T cells and T regulatory cells respectively was then calculated. Cutoffs at 5% and 2.5% were used to define high levels of CD8+ T cells (CD8High) and T regulatory cells (FOXP3High), respectively. In total, 943 patients were analyzed. Results: Among patients who did not receive RT, an increased risk of IBTR and of any recurrence was seen in the CD8Low/FOXP3Low (HR 2.64, CI95% 1.26-5.56, p=0.010 and HR 2.52, CI95% 1.34-4.77, p=0.004, respectively) and CD8High/FOXP3High (HR 1.94, CI95% 0.81-4.63, p=0.135 and HR 2.76, CI95% 1.36-5.57, p=0.005, respectively) groups compared to CD8High/FOXP3Low (HR 1.0) in multivariable analyses including grade and age. The effect of RT on risk of IBTR was more pronounced in the groups with CD8Low/FOXP3Low (HR 0.37, CI95% 0.24-0.57, p&amp;lt;0.001) and CD8High/FOXP3High (HR 0.43, CI95% 0.16-1.13, p=0.086) compared to CD8High/FOXP3Low (HR 0.92, CI95% 0.25-3.40, p=0.905). A potentially unfavorable effect of RT on the risk of any recurrence was observed in the CD8High/FOXP3Low (HR 1.74, CI95% 0.75-4.06, p=0.20) group in contrast to the effect of RT in patients with CD8High/FOXP3High (HR 0.53, CI95% 0.28-1.01, p=0.054) and CD8Low/FOXP3Low (HR 0.48, CI95% 0.34-0.68, p&amp;lt;0.001). A significant interaction between immune phenotype and the effect of RT was found for any recurrence (p=0.024) but not for IBTR (p=0.66). Conclusions: Our findings suggest that patients with a favorable immune phenotype (CD8High/FOXP3Low) may not derive any benefit from adjuvant RT which could be explained by an interaction through which RT may suppress an activated immune response. These results may have an impact on decisions regarding postoperative RT in early breast cancer. Citation Format: Axel Stenmark Tullberg, Henri AJ Puttonen, Erik Holmberg, Dan Lundstedt, Fredrika Killander, Emma Niméus, Anikó Kóvacs, Per Karlsson. A high ratio of CD8/FOXP3 predicts an unfavorable response to postoperative radiotherapy after breast-conserving surgery: Results from the randomized SweBCG91RT trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD6-10.

EP1.18-09 Analysis of the Role of Postoperative Radiotherapy in Pathological N2 Non-Small Cell Lung Cancer with Propensity Score Matching

N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease. For operable patients with postoperative N2 non-small cell lung cancer, the optimum adjuvant treatment strategy is still in dispute. Our aim was to assess the efficacy of conbine postoperative chemoradiotherapy (POCRT) or postoperative chemotherapy (PCT) alone following surgery in pathological N2 non-small cell lung cancer using propensity score matching, and to explore the factors influencing the prognosis. Between 2004 and 2014, a total of 175 patients fulfilled the inclusion criteria. The initiation of PCT started later than 2 weeks after the operation. The regimens of PCT in the present study included a cisplatin-based regimen and were administered for at least 2 cycles. POCRT was executed sequentially or sandwiched with PCT with three-dimensional conformal radiotherapy(3D-CRT) or intensity-modulated radiotherapy technique(IMRT). The prescription dose to clinical target volume (CTV) was 50 (range 44-60) Gy, Data were analyzed using SPSS version 24.0. Survival curves were produced using the Kaplan-Meier estimator method and compared with the log-rank test. Univariable and multivariable analyses of clinical characteristics. All available patient and tumor variables were compared using the χ2 test. Propensity score matching (PSM) analyses were used to compensate for differences in baseline characteristics between the POCRT and PCT groups to confirm the survival difference. The survival of the two groups was followed up and the effect of postoperative radiotherapy was analyzed. The median survival time was 57 vs 40 months in the POCRT and PCT groups, and the 1, 3 and 5-year OS rates in the POCRT and pCT groups were 98.3 vs. 86.1%, 71.7 vs.53.0% and 45.7 vs. 39.0%, respectively (P=0.019). Exploratory subgroup analysis found that compared with PCT, POCRT improved OS in patients with squamous cell subtype (P=0.010), no lymphovascular invasion (P=0.006), pN2a (P=0.006) or total number of metastatic lymph nodes ≤7 (P=0.016). Following PSM, a total of 113 events were identified in both the POCRT and PCT groups, with 60 and 53 patients in each group, respectively. There was no significant difference in the general clinical data between the two groups after matching. The median survival time was 57 vs 63 months in the POCRT and PCT groups after matching, and the 1, 3 and 5-year OS rates in the POCRT and PCT groups were 98.3 vs. 92.5%, 71.7 vs. 64.2% 和 45.7 vs. 50.7% respectively, with no significant difference (P=0.463). Following PSM, the survival differences between POCRT and PCT in the various subgroups were not statistically significant, except in patients with squamous cell lung cancer (P=0.010), there was also a trend toward an increase in the overall survival of pN2-NSCLC with pN2a (P = 0.196) or total number of metastatic lymph nodes ≤7 (P=0.367). Univariate and multivariate analyses indicated that T stage, total number of MLNs and POCRT were independent factors affecting OS. POCRT following complete resection clearly demonstrated superior survival compared with pCT. And POCRT may be specifically recommended to N2 patients with squamous cell lung cancer, particularly those with limited nodal involvement and T4 disease.

Effects of Postoperative Radiotherapy on Vascularized Nerve Graft for Facial Nerve Repair in a Rabbit Model

High fractional dose radiotherapy (RT) produces better radiobiological results. However, a concern always exists regarding radiation-induced damage to normal tissues, in particular, the peripheral nerves. In the present study, we assessed the effects of postoperative RT on vascularized facial nerve grafts in a rabbit model. Surgical defects were created bilaterally on the upper buccal branches of the facial nerve in rabbits. One side received a vascularized nerve graft (VNG), and the other side received a free nerve graft (FNG). RT was planned in 1 group at 1month postoperatively. The dose was equivalent to 60Gy for each side. Evaluation of the facial performance, electrophysiologic monitoring, histologic studies, toluidine blue staining, and scanning electron microcopy were performed at 3months after RT. In the RT group, the pathological changes included surrounding tissue fibrosis, nerve cell shrinkage, Schwann cell injury, and demyelination. Compared with the control group, postoperative RT had no obvious effect on the regeneration and functional recovery of the facial nerves. The functional recovery rate of the VNG was faster than that of the FNG in the RT group. In addition, the difference in the nerve conduction velocity and amplitude was statistically significant between the 2 groups. Postoperative RT influenced the functional recovery of facial nerves to a certain degree. The use of VNGs could alleviate the adverse effects of RT on facial nerve regeneration.

Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes: A Long-Term Follow-Up of the SweBCG91RT Randomized Trial.

The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1,178 patients with breast cancer stage I and II were randomly assigned to breast-conserving surgery plus postoperative RT or breast-conserving surgery only and followed for a median of 15.2 years. Tumor blocks were retrieved from 1,003 patients. Stromal TILs were assessed on whole-section hematoxylin-eosin-stained slides using a dichotomized cutoff of 10%. Subtypes were scored using immunohistochemistry on tissue microarray. In total, 936 patients were evaluated. Altogether, 670 (71%) of patients had TILs less than 10%. In a multivariable regression analysis with IBTR as dependent variable and RT, TILs, subtype, age, and grade as independent variables, RT (hazard ratio [HR], 0.42; 95% CI, 0.29 to 0.61; P < .001), high TILs (HR, 0.61; 95% CI, 0.39 to 0.96, P = .033) grade (3 v 1; HR, 2.17; 95% CI, 1.08 to 4.34; P = .029), and age (≥ 50 v < 50 years; HR, 0.55; 95% CI, 0.38 to 0.80; P = .002) were predictive of IBTR. RT was significantly beneficial in the low TILs group (HR, 0.37; 95% CI, 0.24 to 0.58; P < .001) but not in the high TILs group (HR, 0.58; 95% CI, 0.28 to 1.19; P = .138). The test for interaction between RT and TILs was not statistically significant (P = .317). This study shows that high values of TILs in the primary tumor independently seem to reduce the risk for an IBTR. Our findings further suggest that patients with breast cancer with low TILs may derive a larger benefit from RT regarding the risk of IBTR.

The effect of postoperative radiotherapy on the survival of patients with resectable stage III-N2 non-small-cell lung cancer: a systematic review and meta-analysis.

In the potentially resectable cases of stage III-N2 non-small-cell lung cancer (NSCLC), the optimal post-operative treatment regimen for these patients is uncertain and post-operative radiation therapy (PORT) with chemotherapy is typically recommended. Our aim was to reassess the data of PORT on overall survival (OS) and disease-free survival (DFS) in stage III-N2 NSCLC, in order to figure out whether PORT might lead to a moderate improvement in local control and survival besides resection and adjuvant chemotherapy. A comprehensive search strategy was performed in EMBASE, PubMed, and Cochrane Library for relevant studies comparing PORT combined with adjuvant chemotherapy or adjuvant chemotherapy alone on OS and DFS in resectable stage III-N2 NSCLC. Data were extracted to estimate the effects of PORT on OS and DFS. Eleven studies with 8,928 patients were included. This meta-analysis demonstrated a trend in improving OS associated with the use of PORT (HR=0.88; 95% CI, 0.76 to 1.03; p=0.11) and a significantly difference of effect on DFS associated with the use of PORT (HR=0.78; 95% CI, 0.66 to 0.92; p=0.003). In a subgroup analysis on Caucasian patients, there was a statistically significant benefit (HR=0.88; 95% CI, 0.81 to 0.96; p=0.003) on OS for PORT. Our findings demonstrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT is associated with improved OS and leads to a significantly increased DFS.

Effects of Postoperative Radiotherapy in Early Breast Cancer Patients Older than 75 Years: A Propensity-Matched Analysis.

Background: Currently, there is still some controversy regarding whether early breast cancer patients with a tumor size of ≤5 cm and 1-3 positive lymph nodes should undergo postoperative radiotherapy (PRT).Materials and Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Then, we conducted propensity score matching (PSM), according to the radiotherapy record. The Kaplan-Meier and Cox regression analysis were conducted to explore prognostic factors in breast cancer.Results: A total of 6,777 patients aged 75+ years old were eligible and 2,361 patients were included after PSM. We found PRT could improve patient overall survival (OS) (P = 0.01, hazard ratio [HR] = 0.88, 95% confidence interval [CI], 0.80-0.97). Subgroup analysis revealed PRT could improve OS in patients with hormone receptor positive (HR+) (P = 0.001, HR = 0.84, 95% CI, 0.76 - 0.94) or white patients (P =0.004, HR = 0.86, 95% CI, 0.77 - 0.95).Conclusions: PRT may benefit for elderly women with early breast cancer, especially in HR+ patients or white patients. These findings may inform future optimized options whether elderly female patients with early breast cancer should undergo postoperative radiotherapy.