Adjuvant chemoradiation for gastric carcinoma: State of the art and perspectives

An estimated 990,000 new cases of gastric cancer are diagnosed worldwide each year. Surgical excision, the only chance for prolonged survival, is feasible in about 20% of cases. Even after surgery, the median survival is limited to 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. This led to clinical trials associating surgery with neoadjuvant or adjuvant treatments to improve tumor control and patient survival. The most studied modalities are perioperative chemotherapy and adjuvant chemoradiotherapy. To date, evidence has shown a survival benefit for postoperative chemoradiotherapy and for perioperative chemotherapy. Phase III trials are ongoing to compare these two modalities. The aim of this review is to synthesize current knowledge about adjuvant chemoradiotherapy in the management of gastric adenocarcinoma, and to consider its prospects by integrating modern radiotherapy techniques. Keywords: Gastric cancer, Adjuvant therapy, Chemoradiotherapy, IMRT, Adenocarcinom

Radiotherapy of anal canal cancer

International audienceWe present the update of the recommendations of the French society for radiation oncology on external radiotherapy and brachytherapy of anal canal carcinoma. The following guidelines are presented: indications, treatment procedure, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients

[Purpose] The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients.[Materials and methods] A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction.[Results] The median follow-up was 16 months (range, 1–70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022).[Conclusion] This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy

Impact of pre-radiation therapy quality of life in lung cancer survival: a prospective, intention-to-treat, multicenter study

[Purpose]: Lung cancer (LC) has a significant impact on patients’ health-related quality of life (HRQoL). We investigate the correlations between pre-radiation therapy HRQoL and survival. [Materials and methods]: A prospective, intention-to-treat, multicentre study of 437 patients with LC recruited at the radiation oncology departments of three different institutions was conducted between 2012 and 2016. QoL was assessed using the EORTC-QLQ-C30 (v3.0) and EORTC-QLQ-LC13 questionnaires. Global health status (GHS), physical (PF), role functioning (RF), emotional (EF), cognitive (CF), and social functioning (SF) as well as symptoms scores were evaluated in univariate and multivariate analyses. [Results]: The cohort consisted of 376 men (86%) and 61 women, with a median age of 66 years (range 31–88). Histology was: 72% (n = 315) non-small cell lung cancer and 28% small cell lung cancer. The most common stage was III (80%) and the median follow-up for alive patients was 30 months (range 7–76). Multivariate analysis showed that RF was associated with a lower risk of mortality (HR: 0.693; p = 0.008) and recurrence (HR: 0.737; p = 0.040). Additionally, lower scores on EF and PF were associated with higher mortality (HR: 0.696; p = 0.003 and HR: 0.765; p = 0.044, respectively). Appetite loss, constipation, and dysphagia were associated with a higher risk of mortality (HR: 1.985; p < 0.001, HR: 1.373; p = 0.036, and HR: 1.659; p = 0.002, respectively), while appetite loss was the only symptom associated with a higher risk of recurrence (HR: 1.525; p = 0.014). [Conclusions]: Pre-radiation therapy scores on RF, EF, and PF and symptoms like appetite loss, dysphagia, and constipation were associated with the risk of mortality. This information could be added to other prognostic factors to guide our treatment decisions

Association of single nucleotide polymorphisms at HSPB1 rs7459185 and TGFB1 rs11466353 with radiation esophagitis in lung cancer

[Background and purpose] Radiochemotherapy (RCT) success in lung cancer (LC) can be limited due to the onset of adverse effects in the adjacent normal tissue such as radiation-induced esophageal toxicity (RIET). Therefore, specific biomarkers to customize the RCT dose administration and esophageal toxicity prediction are necessary to improve treatment effectiveness.[Materials and methods] 47 LC patients prospectively recruited between 2012 and 2016 from 3 institutions were genotyped for 7 SNPs along TGFB1 and HSPB1 genes seeking an association with RIET risk development. Kaplan–Meier cumulative probability and Cox proportional hazards analyses were used to evaluate the effect of TGFB1 and HSPB1 genotypes on such risk.[Results] Multivariate analyses showed that patients carrying the HSPB1 rs7459185 CC genotype were associated with a significantly higher risk of acute grade 3 RIET than those carrying the GG/GC genotypes (HR = 17.73; 95% CI = 2.896–108.49; p = 0.002). LC patients who received higher (>median) volume of esophagus exposed to 30 Gy and harboring the rs7459185 GG/GC genotypes showed a significantly lower RIET incidence (p 60 Gy) radiation dose who presented the rs11466353 GG genotype had a significantly lower RIET incidence (p = 0.025).[Conclusion] The presence of different rs7459185/rs11466353 genotypes in LC patients associated with RIET risk and may be useful biomarkers along with other risk factors for guiding therapy intensity in an individualized therapy.This work was supported by grants from Instituto de Salud Carlos III (PI13/01155, PI16/02104) and Consejeria de Salud of the Junta de Andalucia (PI-0096-2012), Spain.Peer reviewe

Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment

[Purpose] Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC).[Materials and methods] Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3–60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12–70]); and 50 (15%) patients underwent surgery.[Results] Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31–88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025).[Conclusions] HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.This work was supported by grants from ISCIII (Fis: PI13/01155, PI16/02104) and Consejeria de Salud of the Junta de Andalucia (PI-0096-2012).Peer reviewe