Surgical resection versus transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Transarterial chemoembolization (TACE) is the gold standard treatment in intermediate hepatocellular carcinoma (HCC), but long-term disease control rates remain low. Herein, we compared results of TACE followed by hypofractionated radiotherapy (TACE-hRT) to surgical resection (SR) in early single or paucinodular intrahepatic HCC. METHODS: Between June 2004 and November 2016, data on 160 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stage A Child-Pugh A HCC treated with SR or TACE-hRT in our expert center were retrospectively reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were evaluated. Clinical outcomes were compared using the stabilized-weights inverse probability of treatment weighting propensity score. RESULTS: Ninety-eight patients underwent SR and 62 were treated by TACE-hRT. Median total dose of RT was 54 Gy (interquartile range [IQR] 54-54) in 3­Gy fractions. Median OS follow-up was 93 months. TTP did not significantly differ between patients following SR and TACE-hRT, with 1­year rates of 68.2% and 82.6% (p = 0.17), respectively. In contrast, PFS and OS were lower in the TACE-hRT group (p = 0.015 and p = 0.006), with a median OS of 37 vs. 63 months for patients with surgery and TACE-hRT, respectively. In multivariate analysis, a significant negative impact on PFS and OS was seen for age at diagnosis, on TTP for alcohol-related liver disease, and on OS for total number of HCC nodules. Symptomatic grade ≥ 3 adverse events were presented by 42 (42.9%) SR and 19 (30.6%) TACE-hRT patients (p = 0.17). CONCLUSION: In patients presenting Child-Pugh A BCLC­A HCC with high risk for surgical complications, TACE-hRT can be an effective and safe treatment. However, surgical management remains the standard of care whenever possible.

Neoadjuvant conformal radiotherapy before liver transplantation for hepatocellular carcinoma: a propensity score matched analysis of postoperative morbidity and oncological results.

Aim: To assess neoadjuvant conformal radiotherapy (CRT) before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) not suitable for standard locoregional treatments. Methods: Patients undergoing OLT for HCC with or without prior CRT were compared using 1:3 propensity score matching. Results: After propensity score matching, 23 patients with CRT were compared with 66 control subjects. Severe morbidity rate was 34.8 versus 24.2% in the CRT and non-CRT groups (p = 0.289). Complete pathological response was observed in 47.8% of CRT-targeted nodules. The 1-/3-/5-year disease-free survivals were 77.3, 77.3 and 68.7% in the CRT group versus 85.4, 68.0 and 61.7% in the non-CRT group (p = 0.829). Conclusion: Conformal radiotherapy represents a satisfactory neoadjuvant therapy for OLT candidates not suitable for standard HCC locoregional therapies.

Chemoradiotherapy of locally advanced nonsmall cell lung cancer: state of the art and perspectives.

PURPOSE OF REVIEW: The treatment of locally advanced nonsmall cell lung cancer (NSCLC) is becoming a significant challenge because of a growing proportion of patients with unresectable or potentially eligible for surgery after a multimodality treatment, stage II to III disease. Despite a multimodality approach consisting in concurrent chemoradiotherapy, the prognosis remains poor. RECENT FINDINGS: Different strategies, including induction and consolidation chemotherapy, chemotherapy regimens, fractionation and radiation doses have been evaluated in phase II and III trials, as well as new therapeutic approaches such as immunotherapy. For patients with resectable stage III disease the optimal strategy remains unclear. The American Society for Radiation and Clinical Oncology and the European Society for Medical Oncology published recent guidelines in 2015. SUMMARY: Concurrent chemoradiotherapy improves overall survival compared with sequential chemotherapy followed by radiation. Adding induction or consolidation chemotherapy to chemoradiotherapy does not appear to improve the outcome. Chemotherapy based on cisplatin combined with radiation is recommended in stage III NSCLC. The standard dose and fractionation of radiotherapy are 60 Gy, one daily fraction of 2 Gy over 6 weeks. Targeted therapies and immunotherapy may improve the management of locally advanced NSCLC in the future.

Conformal radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma: is it safe?

AIM: To report a preliminary experience of conformal radiotherapy (CRT) as bridge to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). METHODS: Data of 12 patients undergoing CRT for HCC followed by OLT between 2012 and 2014 were reviewed. RESULTS: CRT was used in a neoadjuvant or downstaging setting in nine and three patients, respectively. No radiation-related systemic toxicity was observed. Median blood loss and operating time were 1450 ml (600-4000) and 420 min (240-510), respectively. Four patients had diaphragmatic injury. Complete histological response was observed in six patients, and partial response in five. Seven patients developed severe postoperative morbidity including five anastomosis-related complications and one death. CONCLUSION: CRT for HCC provides satisfactory histological response but may compromise OLT safety.

Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial.

OBJECTIVE: The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy. BACKGROUND: Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC. METHODS: Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170). RESULTS: nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P < 0.001), LN downstaging (pN0, 69.1% vs 47.2%, P = 0.016), and reduction in the median NLNr [16.0 (range, 0-47.0) vs 22.0 (range, 3.0-58.0), P = 0.001] and NLNi [0 (range, 0-25) vs 1.0 (range, 0-25), P = 0.001]. A good histological response (TRG1/2) in the resected esophageal specimen correlated with reduced median NLNi [0 (range, 0-10) vs 1.0 (range, 0-4), P = 0.007]. After adjustment by treatment, NLNi [hazards ratio (HR) (1-3 vs 0) 3.5, 95% confidence interval (CI): 2.3-5.5, and HR (>3 vs 0) 3.5, 95% CI: 2.0-6.2, P < 0.001] correlated with prognosis, whereas NLNr [HR (<15 vs ≥15) 0.95, 95% CI: 0.6-1.4, P = 0.807 and HR (<23 vs ≥23) 1.4, 95% CI: 0.9-2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66-0.96, P = 0.018]. CONCLUSIONS: nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection.

Multidisciplinary lung cancer meetings: improving the practice of radiation oncology and facing future challenges.

Clinical guidelines widely recognize the importance of multidisciplinary meetings (MDM) in the optimal care of lung cancer patients. The published literature suggest that dedicated Lung Cancer MDM lead to increased treatment utilization rates and improved survival outcomes for patients with lung cancer. For radiation oncologists, Lung Cancer MDM have been proven to support evidence-based practice and improve the utilization of radiotherapy. Lung Cancer MDM also allow for education and promotion of specialty radiotherapy services. The fast pace of modern medicine is also presenting new challenges for the multidisciplinary lung cancer team, and technological advances are likely to lead to new changes in the structure of traditional Lung Cancer MDM.

FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2).

PURPOSE: To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET1). All included patients had a FDG PET/CT scan during RT (PET2, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year. RESULTS: Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77% received RT with induction chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95% CI 0.73 - 0.94, p < 10(-4)). A SUVmax value of 5.3 in the PET2 scan yielded a sensitivity of 70% and a specificity of 92% for predicting tumour progression or death at 1 year. CONCLUSION: This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).

Bintrafusp Alfa With CCRT Followed by Bintrafusp Alfa Versus Placebo With CCRT Followed by Durvalumab in Patients With Unresectable Stage III NSCLC: A Phase 2 Randomized Study.

INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment. METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point). RESULTS: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression-free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69-3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any-grade treatment-emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%). CONCLUSIONS: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC.

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ Patients with Squamous Cell Anal Cancer, a Subgroup Analysis of the National Multicenter Cohort FFCD-ANABASE.

PURPOSE: The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT. METHODS AND MATERIALS: Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients. RESULTS: The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women. CONCLUSIONS: HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique.

XIAP as a radioresistance factor and prognostic marker for radiotherapy in human rectal adenocarcinoma.

A differential responsiveness of patients to ionizing radiation is observed after preoperative radiotherapy for rectal adenocarcinoma that might be related, in part, to an apoptosis defect. To establish if proteins of the apoptotic cascades [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480) and radiosensitive (SW48) human colorectal cell lines. We demonstrated that, after irradiation, the SW48 cells increased the expression of the pro-apoptotic proteins, whereas the SW480 cells increased the expression of the anti-apoptotic protein XIAP. Moreover, XIAP knockdown in SW480 cells enhanced the basal and radiation-induced apoptotic index; the propensity of the SW480 cells to undergo apoptosis after radiation was higher compared with SW48 cells. In a translational study of 38 patients with rectal carcinoma, we analyzed the apoptotic profile for tumor and noncancerous tissue for each biopsy specimen using IHC. According to their response to preoperative radiotherapy, patients were classified into two groups: responsive and nonresponsive. Although no difference in expression of caspase 3, 8, or 9 was observed in the tumor/normal tissue ratio between responsive and nonresponsive patients, the ratio decreased for DIABLO and increased for XIAP. In conclusion, inhibition of XIAP rescues cellular radiosensitivity and both DIABLO and XIAP might be potential predictive markers of radiation responsiveness in rectal adenocarcinoma.

The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3).

PURPOSE: FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions. The purpose of this study was to investigate the predictive value of FDG PET performed early during CRT (on day 21) in a population of patients with oesophageal squamous cell carcinoma. METHODS: Included in this prospective study were 57 patients with a histological diagnosis of squamous cell carcinoma of the oesophagus. Of these 57 patients, 48 (84%) were evaluated (aged 63 ± 11 years; 44 men, 4 women). Each patient underwent FDG PET (4.5 MBq/kg) before CRT, according to the Herskovic protocol (t0; PET1) and on day 21 ± 3 from the start of CRT (d21; PET2). The response assessment included a clinical examination, CT scan or FDG PET and histological analysis 3 months and 1 year after PET1. The patients were classified as showing a complete response (CR) or a noncomplete response. A quantitative analysis was carried out for PET1 and PET2 using the following parameters: SUVmax, SUVmean (with SUVmean40 as the 3-D volume at an SUVmax threshold of 40% and SUVmeanp as that defined by a physician), tumour volume (TV, with TV40 defined as the TV at 40% of SUVmax, and TVp as that defined by a physician); and the total lesion glycolysis (TLG, SUVmean × TV, with TLG40 defined as the TLG at 40% of SUVmax, and TLGp as that defined by a physician). The differences in responses at 3 months and 1 year between PET1 (t0) and PET2 (d21) were assessed in terms of variations in SUV, TV and TLG using a repeated measures of variance (ANOVA). RESULTS: SUVmax, SUVmean and TLG decreased significantly between PET1 (t0) and PET2 (d21; p < 0.0001). The TV significantly decreased only when assessed as TVp (p = 0.02); TV40 did not decrease significantly. With respect to the predictive value of PET1, only TV40_1 and TVp_1 values, and therefore TLG40_1 and TLGp_1, but not the SUV values, were significantly lower in patients with CR at 3 months. SUVmax1, TVp_1 and TLGp_1 were significantly lower in patients with CR at 1 year. With respect to the predictive value of PET2, only TV40_2 and TVp_2 values, and therefore TLG40_2 and TLGp_2, but not the SUV values, were significantly lower in patients with CR at 3 months. None of the PET2 parameters had significant value in predicting patient outcome at 1 year. The changes in SUVmax, TV40, TVp, TLG40 and TLGp between PET1 and PET2 had no relationship to patient outcome at 3 months or 1 year. CONCLUSION: This prospective, multicentre study performed in a selected population of patients with oesophageal squamous cell cancer demonstrates that the parameters derived from baseline PET1 are good predictors of response to CRT. Specifically, a high TV and TLG are associated with a poor response to CRT at 3 months and 1 year, and a high SUVmax is associated with a poor response to CRT at 1 year. FDG PET performed during CRT on day 21 appears to have less clinical relevance. However, patients with a large functional TV on day 21 of CRT have a poor clinical outcome (ClinicalTrials.gov NCT 00934505).

Treatment Characteristics and Real-World Progression-Free Survival in Patients With Unresectable Stage III NSCLC Who Received Durvalumab After Chemoradiotherapy: Findings From the PACIFIC-R Study.

INTRODUCTION: The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS). METHODS: PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every 2 wk) within an early access program between September 2017 and December 2018. The primary end points are investigator-assessed rwPFS and overall survival (analyzed by Kaplan-Meier method). RESULTS: As of November 30, 2020, the full analysis set comprised 1399 patients from 11 countries (median follow-up duration, 23.5 mo). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% confidence interval: 19.1-24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 versus 19.3 mo) and among patients with programmed cell death-ligand 1 expression greater than or equal to 1% versus less than 1% (22.4 versus 15.6 mo). Overall, 16.5% of the patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis or interstitial lung disease. CONCLUSIONS: Consolidation durvalumab after definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was longer among patients who received concurrent versus sequential CRT and patients with higher programmed cell death-ligand 1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors.

TACE and conformal radiotherapy vs. TACE alone for hepatocellular carcinoma: A randomised controlled trial.

Background & Aims: Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs. classical TACE. Methods: TACERTE was an open-labelled, randomised controlled trial with a 1:1 allocation rate to two or three TACE (arm A) or one TACE + CRT (arm B). Participants had a mean age of 70 years, and 86% were male. The aetiology was alcohol in 85%. The primary endpoint was liver progression-free survival (PFS) in the intention-to-treat population. The typical CRT schedule was 54 Gy in 18 sessions of 3 Gy. Results: Of the 120 participants randomised, 64 were in arm A and 56 in arm B; 100 participants underwent the planned schedule and defined the 'per-protocol' group. In intention-to-treat participants, the liver PFS at 12 and 18 months were 59% and 19% in arm A and 61% and 36% in arm B (hazard ratio [HR] 0.69; 95% CI 0.40-1.18; p = 0.17), respectively. In the per-protocol population, treated liver PFS tended to be better in arm B (HR 0.61; 95% CI 0.34-1.06; p = 0.081) than in arm A. Liver-related grade III-IV adverse events were more frequent in arm B than in arm A. Median overall survival reached 30 months (95% CI 23-35) in arm A and 22 months (95% CI 15.7-26.2) in arm B. Conclusions: Although TACE + CRT tended to improve local control, this first Western randomised controlled trial showed that the combined strategy failed to increase PFS or overall survival and led more frequently to liver-related adverse effects. Impact and implications: Hepatocellular carcinoma is frequently treated by arterial embolisation of the tumour and more recently by external radiotherapy. We tried to determine whether combination of the two treatments (irradiation after embolisation) might produce interesting results. Our results in this prospective randomised study were not able to demonstrate a beneficial effect of combining embolisation and irradiation in these patients. On the contrary, we observed more adverse effects with the combined treatment. Clinical Trials Registration: NCT01300143.

Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE.

INTRODUCTION: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. METHODS: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. CONCLUSION: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial.

INTRODUCTION: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-ßRII (a TGF-ß "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC. METHODS: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1-high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. RESULTS: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1-16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1-15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo-not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo-NR]; hazard ratio = 1.232 [95% CI: 0.885-1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo-NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo-NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796-1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. CONCLUSIONS: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1-high, advanced NSCLC.

The role of radiotherapy in the management of thymic tumors.

Radiotherapy is a major therapeutic modality for thymic malignancies. The exact role of adjuvant radiotherapy after complete resection is still debated for stage II through III tumors. Histology or size, capsular invasion, and even molecular data may be included in the decision making. Radiotherapy may be recommended for stage III thymomas, thymic carcinoma, or after incomplete surgical resection. Combination with chemotherapy may be useful, and must be further evaluated using validated end points, including 5- and 10-year time-to-progression and overall survival. Several initiatives have been taken worldwide to launch collaborative studies in the field, including prospective trials specifically readdressing the role of radiotherapy for thymic malignancies.

Hypofractionation in Early Stage Non-Small Cell Lung Cancer.

Radiation treatment of early stage nonsmall cell lung cancer has evolved over the past 2 decades to progressively more hypofractionated treatment courses. Results comparable to surgical resection are seen with stereotactic body radiotherapy, which is now the standard of care for medically inoperable patients, and a treatment option for operable patients as well. Understanding of the optimal radiation dose and fractionation are evolving, especially for central tumors which have higher treatment toxicity than peripheral tumors.

Lymph Node Dissection in Thymoma: Is it worth it?

OBJECTIVES: Lymph node dissection (LND) and nodal metastases in thymomas remain controversial and understudied. The aim of our study was to evaluate the incidence of nodal metastasis and the short term outcomes of systematic LND in thymomas. MATERIAL AND METHODS: From December 2017 to September 2020, we performed 54 LND conducted according to the International Thymic Malignancy Interest Group (ITMIG) lymph node map. This group was compared to a historical control group of 55 patients who underwent surgery in our center from January 2015 to November 2017. RESULTS: LND was performed in 72 % and in 5 % of the cases in the study cohort group and historical control group, respectively. The number of lymph nodes retrieved was significantly higher in the study cohort group (3.89 per patient vs. 1.62, p = 0.0021). In the whole population studied, nodal metastases were found in 3 patients (2.8 % of all patients) with 5.6 % in the cohort study group vs. 0 % in the control group (p = 0.12). Patients with nodal metastasis had larger tumors (> 7 cm), and a higher histology grade (B2 and B3). There was a trend towards higher risk of laryngeal nerve palsy in the cohort study group (9.3 % vs. 1.8 %, p = 0.11). CONCLUSION: Systematic LND increases the number of lymph node harvested and detects more lymph node metastases, which remains infrequent in thymomas. The impact of LND and the true prognostic significance of lymph node metastases remains controversial. Given the potential complications, LND or sampling should not be perfomed in small, encapsulated and low grade thymomas.

Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.

[Radiotherapy for non-small cell lung cancer]. / Radiothérapie des cancers bronchiques non a petites cellules.

Radiotherapy is a major therapeutic option in non small-cell lung cancer. Concurrent chemoradiation is the standard treatment of locally advanced unresectable tumours. Current modalities of thoracic radiotherapy include three-dimensional conformal techniques, allowing dose escalation and combination with new generation cytotoxic drugs to occur. New techniques of radiotherapy are currently under development: respiratory gating and intensity-modulated techniques may allow a better focalisation of the ballistics; stereotactic radiotherapy and proton-beam radiotherapy, less available in Europe at the time, would be indicated in the exclusive treatment of early-stage tumours in non-operable patients.