High Risk Of Locoregional Recurrence Research Articles

Is postoperative radiotherapy effective in patients with completely resected pathologic stage IIIA(N2) non-small cell lung cancer? High-risk populations should consider it

Background and purposeWe aimed to assess the benefits of postoperative radiotherapy (PORT) in completely resected patients with pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) with a high risk of locoregional recurrence (LRR). Materials and methodsA prospective, randomized trial was conducted starting in July 2016 to explore the optimal timing of PORT in high-LRR-risk patients with completely resected IIIA(N2) NSCLC (NCT02974426). Patients were identified as high-LRR-risk patients via the prognostic index (PI) model and were randomly assigned to PORT-first or PORT-last treatment. To evaluate PORT for high-LRR-risk patients, all patients in this trial constituted the PORT cohort, whereas high-LRR-risk patients without PORT were selected from a retrospective cohort as the non-PORT cohort. Propensity score-matched (PSM) analyses were conducted to compare overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). ResultsBetween 2016 and 2022, 132 patients were included in the trial, with a median follow-up of 49.3 months. The 3-year OS rate was 83.2 %, and the 3-year DFS rate was 35.0 %. Among these patients, 122 patients (92 %) received planned PORT. For 132 intention-to-treat patients, PSM analysis with the non-PORT cohort (n = 307) resulted in 130 matched pairs. The results revealed that PORT improved LRFS (3-year LRFS, 77.6 % vs. 57.3 %; p = 0.00014), DFS (3-year DFS, 35.2 % vs. 28.6 %; p = 0.038), and OS (3-year OS, 83.0 % vs. 60.7 %; p = 0.00017), with no difference in DMFS (p = 0.17). ConclusionPORT could increase local control, DFS, and OS in high-LRR-risk patients with completely resected IIIA(N2) NSCLC. Future research should utilize multidimensional data to pinpoint more precise subgroups benefiting from PORT, with prospective trials validating these findings.

P200 INCIDENCE OF LENVATINIB INDUCED ARTERIAL HYPERTENSION IN THYROID CARCINOMA: A RETROSPECTIVE ANALYSIS OF A SERIES OF CASES

Background and Objective: Advanced thyroid cancer leads to worse overall survival and a higher risk of locoregional recurrence. Tyrosine kinase inhibitors have emerged as a management alternative in these conditions. However, serious adverse effects such as high blood pressure are common in clinical trials and real-life studies. The objective of this study was to evaluate the incidence of arterial hypertension in patients undergoing treatment for advanced thyroid cancer with the tyrosine kinase inhibitors lenvatinib Methods This is a retrospective cohort study of patients with advanced thyroid cancer being managed with Lenvatinib, a tyrosine kinase inhibitor. The incidence of arterial hypertension after the start of treatment was evaluated. Results Among the subjects included in the study (n=26), the mean age was 64.6 ±11.8; 57.7% were women and hypertension occurred in 88.5% (23/26), being CTCAE grade ≥ 3 in 43.5% (10/23). In 12 of 23 it occurred due to exacerbation of pre-existing hypertension and in 10 of 23 it corresponded to de novo hypertension induced by the drug. A patient presented grade 4 hypertension due to posterior reversible encephalopathy syndrome. 6 patients died during follow-up, all developed hypertension during treatment with Lenvatinib. Conclusions: High blood pressure is a common and early adverse effect in the management of advanced thyroid cancer with Lenvatinib. Management strategies to improve drug tolerability may improve disease outcomes, treatment adherence and patient-related outcomes.

Outcomes of adjuvant lymph node field radiotherapy and immunotherapy for stage III melanoma

PurposeWith the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma. Patients and methodsThis retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence. ResultsThirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8–45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7 % for the patients receiving immunotherapy alone (95 % CI: 42.5–82.5 %) and 83.3 % for those receiving radiotherapy and immunotherapy (95 % CI: 48.2–95.6 %; P=0.131). The locoregional progression rate was 24 % in patients receiving immunotherapy and 8 % in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6 % of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events. ConclusionIn patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies.

Protocol for correlation of histological risk assessment/scoring system with a depth of invasion in oral squamous cell carcinoma.

The commonest type of cancer in the head and neck region is oral squamous cell carcinoma (OSCC) due to its high rates of occurrence and mortality. The early diagnosis of oral cancer gives better prognosis. Brandwein-Gensler criteria predict the early stage of OSCC cases with a high risk of locoregional recurrence. To correlate Brandwein-Gensler criteria and depth of invasion of OSCC with three-year survival. In the study, This study will include 80 random histopathologically-diagnosed cases of OSCC. hematoxylin-eosin (HE)-stained section slides will be used to evaluate, Brandwein and Gensler criteria by three histopathologists in a blinded manner. The depth of invasion assessment will be done from the basement-membrane (BM), in regions where the BM has been lost, as well as from an illustrative line connecting the BM from the neighbouring epithelium to the point of deepest tumour invasion in the connective-tissue stroma with the help of a research microscope (Leica-DMLB2) in resected tissue specimens of OSCC cases. The present study will find the correlation between Brandwein-Gensler criteria and depth of invasion in OSCC in order to evaluate the locoregional recurrence in OSCC cases. In high-risk OSCC cases, there may be an increased depth of invasion in resected tissues. We hypothesized that the correlation between Brandwein-Gensler criteria and depth of invasion can be used as an independent predictor for locoregional recurrence in OSCC.

Whole-exome sequencing reveals an association of rs112065068 in TGOLN2 gene with distant metastasis of non-small cell lung cancer

Early prediction and prevention of recurring illness is critical for improving the survival rates of patients with non-small cell lung cancer (NSCLC). Previously, we demonstrated that the presence of premalignant epithelial changes in the small bronchi distant to the primary tumor is associated with NSCLC progression: isolated basal cell hyperplasia (iBCH) indicates a high risk of distant metastasis, BCH combined with squamous metaplasia (BCHSM) – a high risk of locoregional recurrence. Here, we aimed to identify germline single nucleotide variants (SNVs) and insertions and deletions (InDels) associated with distant metastasis and locoregional recurrence in cases with iBCH and BCHSM using whole-exome sequencing of 172 NSCLC patients. The rs112065068 of the TGOLN2 gene was identified only in iBCH patients and was associated with a high risk of distant metastasis (P < .001) and worse metastasis-free survival (HR = 4.19 (95 %CI 1.97–8.93); P < .001). This variant was validated in a group of 109 NSCLC patients using real-time PCR and Sanger sequencing analyses. To our knowledge, this study is the first to identify a germline variant associated with NSCLC distant metastasis.

Impact of Radiation Therapy Modalities on Loco-regional Control in Inflammatory Breast Cancer

In inflammatory breast cancer, radiation therapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiation therapy modalities on the risk of loco-regional and distant relapse. This retrospective multicenter study included patients with localized inflammatory breast cancer treated between 2010 and 2017. Standard postmastectomy radiation therapy consisted of daily fractions to a total dose of 50 Gy equivalent without a boost or bolus, while intensified radiation therapy referred to the use of a boost or bolus. The cumulative incidence curves of locoregional and distant recurrence were displayed using the competing risk method. Of the 241 included patients, 165 were treated with standard and 76 with intensified radiation therapy. There was significantly more nodal involvement in the intensified group. With a median follow-up of 40 months postradiation therapy, there was no difference between standard versus intensified radiation therapy regarding the cumulative incidence of locoregional (P = .68) or distant recurrence (P = .29). At 5 years, the risks of locoregional and distant recurrence were 12.1% (95% CI, 7.5; 17.7) and 29.4% (95% CI, 21.8; 37.3) for patients treated with standard radiation therapy and 10.4% (95% CI, 4.4; 19.3) and 21.4% (95% CI, 12.6; 31.9) for those treated with intensified radiation therapy. In multivariate analyses, triple-negative subtype and absence of complete pathologic response were associated with a higher risk of loco-regional recurrence. Radiation therapy intensification had no significant impact on locoregional and distant recurrence. For patients with a non-complete pathologic response (n = 172, 71.7%), no significant differences were observed between the 2 groups for loco-regional (P = .80) and distant (P = .39) recurrence. Severe toxicity rates were similar in both groups. Contrary to other important series, this large retrospective multicentric study did not show a locoregional or distant control benefit of intensified radiation therapy. Pooled prospective studies and meta-analyses of intensified radiation therapy are warranted to endorse this approach.

Protocol for correlation of histological risk assessment/scoring system with a depth of invasion in oral squamous cell carcinoma

Introduction: The commonest type of cancer in the head and neck region is oral squamous cell carcinoma (OSCC) due to its high rates of occurrence and mortality. The early diagnosis of oral cancer gives better prognosis. Brandwein-Gensler criteria predict the early stage of OSCC cases with a high risk of locoregional recurrence. Objectives: To correlate Brandwein-Gensler criteria and depth of invasion of OSCC with three-year survival. Methodology: In the study, hematoxylin-eosin (HE)-stained section slides will be used to evaluate Brandwein and Gensler criteria and depth of invasion in resected tissue specimens of OSCC cases. Expected results: The present study will find the correlation between Brandwein-Gensler criteria and depth of invasion in OSCC in order to evaluate the locoregional recurrence in OSCC cases. In high-risk OSCC cases, there may be increased depth of invasion in resected tissues. Conclusions: We hypothesized that the correlation between Brandwein-Gensler criteria and depth of invasion can be used as an independent predictor for locoregional recurrence in OSCC.

Next-Generation Sequencing Analysis of Mutations in Circulating Tumor DNA from the Plasma of Patients with Head-Neck Cancer Undergoing Chemo-Radiotherapy Using a Pan-Cancer Cell-Free Assay.

Using next-generation sequencing (NGS), we investigated DNA mutations in the plasma tumor cell-free circulating DNA (ctDNA) of 38 patients with inoperable squamous cell head neck cancer (SCHNC) before and after the completion of chemoradiotherapy (CRT). Baseline mutations of the TP53 were recorded in 10/38 (26.3%) and persisted in 4/10 patients after CRT. ΤP53 mutations were further detected post CRT in 7/38 additional patients with undetectable mutations at baseline (overall rate 44.7%). Furthermore, 4/38 patients exhibited baseline mutations of the EGFR, AR, FGFR3, and FBXW3, and four new gene mutations were detected after CRT (MTOR, EGFR3, ALK, and SF3B1). Τ4 stage was related with a significantly higher rate of mutations (TP53 and overall). Mutations were observed in 8/30 (26.6%) responders (complete/partial response) vs. in 6/8 (75%) of the rest of the patients (p = 0.03). Significant poorer LRFS was noted for patients with mutations detected before and after CRT (p = 0.02). Patients who had detectable mutations either before or after CRT had significantly worse DMFS (p = 0.04 overall, and p = 0.02 for TP53 mutations). It was concluded that assessment of mutations before and after the end of CRT is essential to characterize patients with a high risk of locoregional recurrence or metastatic progression.

Thyroid metastasis from nasopharyngeal cancer: a case report

Background. Nasopharyngeal cancer is a rare head and neck cancer with a relatively high risk of locoregional recurrence and distant metastases. The most common sites of metastases are bones (70–80 %) followed by liver (30 %), lung (18 %), and lymph node (axillary, mediastinal, pelvic, and inguinal). Thyroid gland is an uncommon site of metastasis with an incidence ranging from 0.5% to 24 %. Thyroid metastasis from nasopharyngeal cancer has been reported in only 9 cases in the world literature and no one in Russia. Case report. We report a case of thyroid metastasis from nasopharyngeal cancer found incidentally in a 53-year-old female patient. Conclusion. Metastases to the thyroid gland are rare, and patients with metastatic thyroid disease rarely present with organ-specifc symptoms, thus raising diagnostic diffculties for both clinicians and the pathologists. This clinical report demonstrates the diffculties of differential diagnosis,as well as the importance of a thorough collection of complaints, anamnesis, and clinical examination.

Molecular risk factors for locoregional recurrence in resected non-small cell lung cancer.

Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non-small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. A total of 118 patients who underwent tumor resection with mutation-detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3-year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR-free survival as compared to patients with wild-type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Abstract P4-07-17: Follow-up in breast cancer care: guidelines and individual risks

Abstract The aim of this study was to investigate how breast cancer follow-up in the Netherlands changed during the COVID-19 pandemic, compared to 2018-2019, and to what extent follow-up during the pandemic corresponded to the patient risk of recurrence. During the early phase of the pandemic the Dutch Society for Surgical Oncology (NVCO) issued a report with recommendations on how follow-up could be postponed, as a guidance for the pandemic, based on a low, intermediate or high risk of recurrence. In this study we investigated to what extent this advice was followed. A dataset of 33160 women diagnosed with primary invasive breast cancer between January of 2017 and July of 2021 was selected from the Netherlands Cancer Registry (NCR) and Dutch Hospital Data (DHD). The pandemic, 2020 and weeks 1-32 of 2021, was divided into six periods (A to F), based on the number of hospitalized COVID patients in the Netherlands. The five-year risk of locoregional recurrence (LRR) was determined for each patient with the INFLUENCE nomogram. The LRR risk was compared to the risk groups from the NVCO report with a Kruskal-Wallis test. The percentage of patients who received a mammogram during period A to F was compared to the same periods of 2018-2019 with a chi-squared test. Correlation between the LRR risk, and if patients had a mammogram, was investigated with logistic regression. This analysis was repeated separately for the risk groups. Correlation between the LRR risk, and time intervals between surgery and the first and second mammogram was analyzed using cox proportional hazard models, this was also repeated for the risk groups. There was a significant difference in LRR risk between the NVCO risk groups. In the low-risk group (n=7673), 86 patients (1.1%) had a risk &amp;gt;5%. In the intermediate risk group (n=19197), 18364 patients (95.7%) had a risk of &amp;lt; 5%, and 65 patients (0.34%) had a risk of &amp;gt;10%. In the high-risk group (n=2674), 2365 patients (88.4%) had a risk &amp;lt; 10%. The percentage of patients who received a mammogram was significantly lower in periods B to F of the pandemic. Logistic regression showed a negative correlation between the risk of LRR and if patients had a mammogram in 2020 (OR 0.93) and 2021 (OR 0.93). There was also a negative correlation between the risk groups and mammography in 2020 (OR 0.92 for intermediate and 0.80 for high), and for the risk groups and mammography in 2021 (OR 0.98 for intermediate and 0.95 for high). There was no significant impact of LRR risk, or risk group, on time intervals between mammograms. During the pandemic, patients with a higher LRR risk, or a higher risk according to NVCO advice, had lower odds of having a mammogram. If the advice would have been followed, in 0.5% of the patients scheduled for follow-up, the recommendation was to postpone in contrast to a high estimation of the individual risk. For 62.7%, a follow-up was recommended, despite a low estimated individuals risk. Because the number of high-risk patients is relatively low, individual risk prediction could be supportive, in case of future restrictions. This way the high-risk patients can be identified and prioritized for follow-up, and can also be encouraged to come to the hospital. Citation Format: Lotte Van Dongen, Joyce Meijer, Jolanda Van Hoeve, Desiree van den Bongard, Marielle Hendriks, Aafke Honkoop, Luc Strobbe, Cristina Guerrero Paez, Sabine Siesling. Follow-up in breast cancer care: guidelines and individual risks [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-17.

Margin Free Resection Achieves Excellent Long Term Outcomes in Parathyroid Cancer.

Long-term outcomes of parathyroid cancer remain poorly documented and unsatisfactory. This cohort includes 25 consecutive parathyroid cancer patients with median follow-up of 10.7 years (range 4.1-26.5 years). Pre-operative work-up in the center identified a suspicion of parathyroid cancer in 17 patients. En bloc resection, including the recurrent laryngeal nerve in 4/17 (23.5%), achieved cancer-free resection margins (R0) in 82.4% and lasting loco-regional disease control in 94.1%. Including patients referred after initial surgery elsewhere, R0 resection was achieved in merely 17/25 (68.0%) of patients. Cancer-positive margins (R1) in 8 patients led to local recurrence in 50%. On multivariate analysis, only margin status prevailed as independent predictor of recurrence free survival (χ2 19.5, p &lt; 0.001). Local excision alone carried a 3.5-fold higher risk of positive margins than en bloc resection (CI95: 1.1-11.3; p = 0.03), and a 6.4-fold higher risk of locoregional recurrence (CI95: 0.8-52.1; p = 0.08). R1-status was associated with an 18.0-fold higher risk of recurrence and redo surgery (CI95: 1.1-299.0; p = 0.04), and a 22.0-fold higher probability of radiation (CI95: 1.4-355.5; p = 0.03). In patients at risk, adjuvant radiation reduced the actuarial risk of locoregional recurrence (p = 0.05). When pre-operative scrutiny resulted in upfront oncological surgery achieving cancer free margins, it afforded 100% recurrence free survival at 5- and 10-year follow-up, whilst failure to achieve clear margins caused significant burden by outpatient admissions (176 vs. 4 days; χ2 980, p &lt; 0.001) and exposure to causes for concern (1369 vs. 0 days; χ2 11.3, p = 0.003). Although limited by cohort size, our study emphasizes the paradigm of getting it right the first time as key to improve survivorship in a cancer with excellent long-term prognosis.

Review for N2 Sub-staging in Non-small Cell Lung Cancer

Patients with N2 non-small cell lung cancer (NSCLC) were heterogeneous groups and required further stratification. The International Society for the Study of Lung Cancer (IASLC) divided N2 into three sub-stages: N2 at a single station without N1 involvement (N2a1), N2 at a single station with N1 involvement (N2a2), and N2 at multiple stations (N2b). These new descriptors significantly distinguished the overall survival (OS), disease-free survival (DFS), and recurrence pattern of patients with different N2 sub-stages. The OS and DFS of N2a1 were not sufficiently distinguished from N1 at multiple stations (N1b). The OS and DFS of N2a2 were intermediate between those of N2a1 and N2b. Current evidence did not support the further subdivision of the N2b. The main recurrence pattern of N2a1, N2a2 and N2b were distant metastasis, and the risks of distant metastasis increased successively. N2a1 patients were at low risk of locoregional recurrence, which could not be reduced by postoperative radiotherapy (PORT). N2a2 and N2b patients had a similar higher risk of locoregional recurrence, which could be reduced to a similar level of N2a1 patients by PORT. .

Development and Validation of a Decision Support Framework to Evaluate the Role of Postoperative Radiotherapy in Patients with Pathological N2 Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Postoperative radiotherapy (PORT) plays a highly controversial role in pN2 NSCLC disease. Recent study revealed that not all patients can benefit from PORT. Further study is needed to identify predictors for PORT. <h3>Materials/Methods</h3> A total of 1044 patients with completely resected pathologic stage T1-3N2M0 NSCLC were analyzed. Risk factors of distant metastasis were identified by the log-rank tests and the multivariable Cox models. The decision support framework (DSF) was built based on the previously published PI model and risk factors of distant metastasis. An independent dataset was used to validate the DSF. <h3>Results</h3> Clinical N2 status (HR=1.227, 95% CI 1.036 to 1.453, P=0.0178) and >4 involved lymph nodes (HR=1.272, 95% CI 1.071 to 1.510, P=0.0058) were identified as independent risk factors of distant metastasis and were also found to be associated with locoregional recurrence (LRR) in our previous work. The high-intermediate-risk histological type (micropapillary or solid positive adenocarcinomas) was found to be associated with distant metastasis (HR=1.207, 95% CI 1.062 to 1.371, P=0.0129), but not associated with LRR. We built an DSF accordingly and stratify patients into four groups: high LRR risk and high-intermediate histological risk (HHR) group, high LRR risk and low histological risk (HLR) group, low LRR risk and high-intermediate histological risk (LHR) group, and low LRR risk and low histological risk (LLR) group. PORT significantly improved OS only in the subgroup with a high risk of LRR and low-risk histological type (3-year OS rates: 66.7% for PORT vs. 50.2% for non-PORT, respectively; P=0.023). In the HHR group, PORT was associated with a not significant increase in OS. In the LLR and the LHR groups, no significant differences in OS were observed between PORT and non-PORT. <h3>Conclusion</h3> This study developed and validated a DSF combining two types of clinicopathological characteristics to predict the outcome of PORT in patients with completely resected pN2 NSCLC individually.

Re-Irradiation of Lung Lesions by Stereotactic Ablative Radiotherapy

<h3>Purpose/Objective(s)</h3> Patients with primary lung cancer or other primary cancers have a high risk of loco-regional recurrence or pulmonary metastases requiring thoracic re-irradiation. Only very limited data about lung re-irradiation exist. Stereotactic Ablative Radiotherapy (SABR) was used in various clinical situations and several attempts have been made to apply SABR to lung lesions previously irradiated. Nevertheless, the use of high dose in the re-irradiation is not without risks. Aim of this study is to evaluate the outcomes of re-irradiation by SABR in terms of Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) and to assess the toxicities and predictive factor of response. <h3>Materials/Methods</h3> From April 2011 to April 2021, 43 patients received a re-irradiation by SABR in the lung on 58 lesions. Primary cancer was lung in 72%, colon-rectal in 14%, and 14% others. Thirty-four lesions were retreated in the same lobe, 14 in the adjacent lobe, 10 in the contra-lateral lung. Four lesions had a central localization, 54 lesions had a peripheral location. The medium volume was 33.4cc (range: 0.9-260.8cc). The medium BED(10) of first treatment was 103.1 Gy (range: 39-151.2 Gy). The medium BED(10) of re irradiation by SABR was 95.34 Gy (range: 39-151.2 Gy). Thirteen lesions received 1 fraction, 45 multiple fractions (range:3-10 fractions). The schedules most represented for re-irradiation were 30 Gy in 1 fraction, 45 Gy in 3 fractions and 54 Gy in 3 fractions. <h3>Results</h3> Rates of LC at 1, and 3 years were 51% and 43%, respectively. Rates of PFS at 1, and 3 years were 38% and 21% respectively. The median OS was 32 months (range: 3–131 months), Rates of OSat 1, and 3 years were 77% and 43%. In the univariate analysis the single fraction vs. multiple fractions, and the volume (<33.4 cc) showed a statistically significant correlation with LC (P= 0,0032 and P=0,0008, respectively) and PFS (P= 0,0080 and P=0,0258). In the univariate analysis, the single fraction vs. multiple fractions showed a statistically significant correlation also with OS (P = 0,0014). In terms of acute toxicity, 26% side effects were observed, 7 cases Grade 1 (in the form of dyspnea, cough and dysphagia) and 8 cases Grade 2 (in the form of dyspnea, cough, brachial plexopathy, pain and esophageal hemorrhage). In terms of late toxicity 39% side effects were observed, 11 cases Grade 1 (in the form of dyspnea, atelectasis, fibrosis, rib fracture, pain and asthenia), 10 cases Grade 2 (in the form of dyspnea, gastro-esophageal reflux, soft tissue necrosis, pulmonary fibrosis, pleural effusion and asthenia) and 2 cases Grade 3 occurring in the form of pain and dyspnea. <h3>Conclusion</h3> SABR re-irradiation can play a role in prolonging survival in lung recurrence with an acceptable toxicity. However, more knowledge is necessary to mitigate the risk of severe toxicity.

671P Postoperative chemoradiation in combination with cetuximab followed by 6-months cetuximab maintenance in squamous cell carcinoma of the head and neck with high risk of locoregional recurrence

Post-surgery chemoradiation (pCRT) is standard in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), although there is still a need to improve the outcome. We performed an open-label, single-arm, multicenter trial (EudraCT No. 2007-002659-17) and investigated safety and efficacy of escalating the multimodal therapy by adding concomitant and maintenance cetuximab (CTX).

Prognostic significance of AKR1C4 and the advantage of combining EBV DNA to stratify patients at high risk of locoregional recurrence of nasopharyngeal carcinoma

BackgroundDistinguishing patients at a greater risk of recurrence is essential for treating locoregional advanced nasopharyngeal carcinoma (NPC). This study aimed to explore the potential of aldo–keto reductase 1C4 (AKR1C4) in stratifying patients at high risk of locoregional relapse.MethodsA total of 179 patients with locoregionally advanced NPC were grouped by different strategies; they were: (a) divided into two groups according to AKR1C4 expression level, and (b) classified into three clusters by integrating AKR1C4 and Epstein-Barr virus (EBV) DNA. The Kaplan–Meier method was used to calculate locoregional relapse-free survival (LRFS), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The Cox proportional hazards model was used to determine potential prognostic factors, and a nomogram was generated to predict 3-year and 5-year LRFS.ResultsA significant difference in the 5-year LRFS was observed between the high and low AKR1C4 expression groups (83.3% vs. 92.7%, respectively; p = 0.009). After integrating AKR1C4 expression and EBV DNA, the LRFS (84.7%, 84.5%, 96.9%, p = 0.014) of high-, intermediate-, and low- AKR1C4 and EBV DNA was also significant. Multivariate analysis indicated that AKR1C4 expression (p = 0.006) was an independent prognostic factor for LRFS. The prognostic factors incorporated into the nomogram were AKR1C4 expression, T stage, and EBV DNA, and the concordance index of the nomogram for locoregional relapse was 0.718.ConclusionsIn conclusion, high AKR1C4 expression was associated with a high possibility of relapse in NPC patients, and integrating EBV DNA and AKR1C4 can stratify high-risk patients with locoregional recurrence.

A decision support framework for postoperative radiotherapy in patients with pathological N2 non-small cell lung cancer

IntroductionPostoperative radiotherapy (PORT) plays a highly controversial role in pathological N2 (pN2) non-small cell lung cancer (NSCLC) disease. Recent studies reveal that not all patients can benefit from PORT. Further research is needed to identify predictors of PORT. MethodsA total of 1044 pathologic stage T1-3N2M0 NSCLC patients were analyzed. Risk factors of distant metastasis were identified by the log-rank tests and the multivariable Cox models. We integrated risk factors of distant metastasis and our previously published loco-regional recurrence (LRR) related prognostic index into a decision support framework (DSF) to predict the outcomes of PORT. An independent cohort was used to validate the DSF. ResultsWe defined patients with more than two of three identified LRR-related features (heavy cigarette smoking history, clinical N2 status, and more than four positive lymph nodes) as a high LRR risk group. We found the high-intermediate-risk histological type (with micropapillary and/or solid components) was associated with a higher risk of distant metastasis (HR = 1.207, 95 % CI 1.062 to 1.371, P = 0.0038), but not LRR. We built the DSF by combining these two types of features. Patients were stratified into four groups by using the DSF. PORT significantly improved OS only in the subgroup without high-risk histological features (without micropapillary or solid components) and with a high risk for LRR (three-year OS: 66.7 % in the PORT group vs 50.2 % in the non-PORT group; P = 0.023). ConclusionsA particular pN2 subgroup with a high risk of LRR and without micropapillary or solid components could benefit from PORT.

Postoperative locoregional recurrence pattern and treatment management of stage pT4 sigmoid colon cancer: a retrospective cohort study

BackgroundThis study aimed to explore the pattern of locoregional recurrence after surgery in patients with non-metastatic stage pT4 sigmoid colon cancer and the role of adjuvant radiotherapy on survival.MethodsWe retrospectively analyzed data from 208 patients who underwent surgery in our hospital. The patients were randomly divided into training and validation groups at a 1:1 ratio. Patients at high risk for locoregional recurrence were screened using Cox regression analysis. Based on the data of 2,886 patients in the Surveillance, Epidemiology, and End Results (SEER) database, the effect of adjuvant radiotherapy on overall survival (OS) and cancer-specific survival (CSS) was evaluated by Kaplan–Meier curves.ResultsOf the 208 patients, 57 (27.4%) presented with locoregional recurrences (14 anastomotic and 43 abdominal or pelvic lymph node recurrences). Multivariate analysis showed that serum CEA, differentiation, lymph node dissection number, and N stage were independent predictors of locoregional recurrence-free survival (all p < 0.05). A risk-stratification model was constructed, and a total score of ≥ 6.5 points was considered the high-risk group for locoregional recurrence. Both the training and validation sets presented that the model had a good predictive ability (area under the curve = 0.828 and 0.724, respectively). Analysis of SEER data revealed that adjuvant radiotherapy significantly prolonged OS and CSS in the high-risk population (all p < 0.05, vs. no radiotherapy).ConclusionsPatients with a total risk score of 6.5 or more had a high likelihood of locoregional recurrence, and perhaps adjuvant radiotherapy could improve their survival.

Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma.

Simple SummaryA high risk of relapse and treatment resistance are among the major challenges in locally advanced head and neck squamous cell carcinoma (HNSCC). Data show that common germline alterations in genes regulating angiogenesis may modulate treatment sensitivity, cancer progression, and prognosis, but relatively little is known about their role in HNSCC. Thus, our goal was to examine the effect of variation in these genes on survival outcomes in HNSCC patients receiving radiotherapy and cisplatin-based chemoradiotherapy. We identified genetic variants significantly affecting therapy results, constituting independent prognostic factors in these patients. Our results suggest that some polymorphisms in angiogenesis genes may be determinants of treatment efficacy and tumor aggressiveness in HNSCC, which may be of importance in standard therapy. These findings emphasize the potential value of the host genetic profile related to angiogenesis in assessing the risk of treatment failure.Fibroblast growth factor (FGF)/FGF receptor (FGFR), and platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) systems, as well as some matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in various steps of angiogenesis. Data indicate that common germline variations in angiogenesis-regulating genes may modulate therapy results and cancer progression. However, whether these variants affect clinical outcome in head and neck squamous cell carcinoma (HNSCC) is unclear. Hence, we assessed the relationship between FGF/FGFR, PDGF/PDGFR, MMP, and TIMP genetic variants and treatment outcomes in HNSCC patients receiving radiotherapy (RT) alone or combined with cisplatin-based chemotherapy. In multivariate analysis, FGF2 rs1048201 CC homozygotes showed a higher risk of death (p = 0.039), while PDGFRA rs2228230 T was strongly associated with an increased risk of locoregional relapse (HR 2.49, p = 0.001) in the combination treatment subgroup. In the RT alone subset, MMP2 rs243865 TT carriers had a higher risk of locoregional recurrence (HR 2.92, p = 0.019), whereas PDGFRB rs246395 CC homozygotes were at increased risk of metastasis (HR 3.06, p = 0.041). The MMP2 rs7201 C and TIMP2 rs7501477 T were associated with a risk of locoregional failure in the entire cohort (p = 0.032 and 0.045, respectively). Furthermore, rs1048201, rs2228230, rs246395, rs243865, rs7201, and rs7201/rs7501477 were independent indicators of an unfavorable outcome. This study demonstrates that the FGF2, PDGFRA, PDGFRB, MMP2, and TIMP2 variants may contribute to treatment failure and poor prognosis in HNSCC.