Consolidation Radiotherapy Research Articles

The Theoretical Role for Radiotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Secondary Analysis of a Prospective Randomized Controlled Trial.

The role of radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) is unclear. In patients treated with upfront chemotherapy for DLBCL, indications for RT are often considered to be bulky (7.5 cm +) or extranodal disease. This is thought to improve outcomes through improvement in local control. Many trials call into question the actual benefit of RT. Alliance/CALGB 50303 was a randomized phase III trial comparing two chemotherapy regimens for the treatment for DLBCL in which no patients were to receive RT. Our objective was to assess the theoretical impact of RT by assessing outcomes of trial patients. This secondary analysis was performed using PET/CT images and data from the NCTN/NCORP Data Archive of the National Cancer Institute. Data were originally collected on the Alliance/CALGB 50303 (NCT00118209) clinical trial. Of the 524 registered patients, data and images for 155 patients were available. Two investigators measured the largest sites of nodal involvement on PET/CT and the average was calculated-the largest was used to determine bulky disease. Bulk was defined as nodal disease with maximum diameter greater than or equal to the threshold. Thresholds (in cm) examined included: 5, 6, 7, 7.5, 8, 9, and 10. PFS was estimated for patients with versus without bulky disease and compared using the log-rank test. Of the 155 evaluable pre-treatment PET/CT image sets, 135 patients had measurable nodal disease. Fifteen patients who did not complete treatment per protocol and four patients with mediastinal B-cell lymphoma were excluded. Of the 116 analyzed patients, 45% had stage IV disease, 88% had an ECOG performance status of 0-1, and one had double-hit lymphoma. IPI was 0-2 in 62% and 3-5 in 38%. Chemotherapy was R-CHOP in 61 and DA-R-EPOCH in 55. Best response was CR in 84 patients (73%), PR in 30 (26%) and SD in 1 (1%). The median follow-up was 5 years and 32 PFS events were observed. Bulky disease was associated with elevated LDH at diagnosis (using 7.5 cm threshold: LDH elevated in 72% with bulky disease v. 40% with non-bulky, p< 0.01) and more frequent use of pegfilgrastim (51% v. 31%, respectively, p = 0.04). Overall, the 5-year PFS rate was 72.3% (95% CI 64.1-81.4). Using a 7.5 cm threshold, 5-year PFS was 62.7% in patients with bulk versus 79.3% in those without (p = 0.14). There were no significant PFS differences (p>0.05) observed at any threshold. The 5-year OS was 86.4% (95% CI 80.2-93.1); no differences in OS by bulk using any threshold were observed. In this secondary analysis of a phase III randomized trial of chemotherapy alone for DLBCL, initial bulk was not shown to be significantly associated with outcomes. Prospective data comparing consolidative RT versus no RT are necessary to determine optimal treatment paradigms.

Impact of Consolidative Radiation on Overall and Progression Free Survival in Pediatric, Adolescent and Young Adult Metastatic Sarcoma

To determine the association between consolidative radiation and survival in pediatric, adolescent, and young adult (AYA) metastatic sarcoma MATERIALS/METHODS: Eligible patients included those diagnosed with metastatic bone or soft tissue sarcoma at ≤39 years of age. Patients whose cancer progressed prior to the time of local control were excluded. Consolidative radiation (RT) was defined as RT to all sites of metastatic disease. Kaplan Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cox proportional hazards was used to account for confounding variables. To adjust for immortal time bias (ITB), end of local control was chosen as a landmark time. Patients (n = 77) had a median age at diagnosis of 14.5 years (range: 1.7-29.7 years). The most common histology was Ewing sarcoma (49%), followed by rhabdomyosarcoma (30%). Median follow up was 28.5 months, without significant difference between patients treated with and without consolidative RT (23.7 vs. 21.5 months, p = 0.270). Median time to completion of consolidative RT from diagnosis was 8.5 months. Ewing sarcoma was more likely to be treated with consolidative RT compared to other histologies (p<0.001). Consolidative RT was associated with improved OS (2yr OS: 81.9% vs. 57.9%, p = 0.009) and PFS (2yr PFS: 71.2% vs. 30%, p = 0.001). On multivariate analysis, after accounting for age, histology, number, and type of metastases (lung, bone or other), consolidative RT remained independently associated with improved OS (hazard ratio (HR):0.36, 95% confidence interval [CI]: 0.17, 0.78, p = 0.010) and improved PFS (HR = 0.34, 95% CI = 0.16, 0.73, p = 0.006). The OS benefit for consolidative RT persisted after adjusting for ITB (1yr OS post-local control: 80.9% vs. 89.7%, p = 0.016). The effect of consolidative RT was validated in a dataset consisting of patients who were diagnosed with localized disease but had metastatic progression (n = 30). In this metachronous population, consolidative RT remained independently associated with improved OS (HR = 0.11, 95% CI = 0.03, 0.51, p = 0.004) after accounting for age. ConsolidativeRT was independently associated with improved OS and PFS in pediatric and AYA patients with metastatic sarcoma at diagnosis. The OS benefit extended to those who underwent consolidative RT for metastatic progression. Future work should evaluate biomarkers to optimize patient selection and timing and dose of consolidative RT.

Consolidative Radio therapy in Place of Autologous Stem Cell Transplant in Patients with Low-Risk Relapsed/Refractory (R/R) Classic Hodgkin Lymphoma (cHL) Treated with Nivolumab plus Brentuximab Vedotin: CheckMate 744

Standard of care treatment for patients with relapsed and refractory classic Hodgkin lymphoma (RRHL) involves second line therapy followed by high dose therapy and autologous stem cell transplant (HDT/ASCT) and carries with it significant costs and toxicities to the patient. Some patients with RRHL may not require such intensive therapy, especially in the era of targeted chemotherapy and checkpoint inhibitors. CheckMate 744 (NCT02927769) evaluated a novel second-line therapy that omits HDT/ASCT by combining brentuximab vedotin (BV) and a nivolumab (N) followed by consolidative ISRT for low risk RRHL. Pts were aged 5-30 y and had one prior treatment without HDT/ASCT. Low-risk RRHL were those at relapse without B symptoms or extranodal disease, limited sites of relapse (≤4 sites of disease above the diaphragm or ≤3 sites above/below the diaphragm) AND with initial Stage IA, IIA with relapse <1 year if they received ≤3 cycles of chemotherapy and no RT OR Stage IA/B, IIA/B, IIIA ≥ 1 year. Patients received 4 cycles of N + BV induction. Patients with complete metabolic response (CMR) received an additional 2 cycles of N + BV before RT consolidation. Patients with suboptimal response received 2 cycles of BV + bendamustine intensification. Those patients achieving CMR proceeded to RT consolidation. RT was delivered to a dose of 30-30.6 Gy at 1.5-1.8 Gy/fraction to an ISRT volume. Among 28 pts treated, the median age (range) was 17 (6-27) years old and 64% of patients were aged < 18 y. Most (79%) pts had stage II disease at diagnosis and 82% had relapsed ≥ 12 months after first line treatment. Of 27 pts continuing in study after induction N + BV, 6 received bendamustine + BV intensification, and 92.9% achieved complete metabolic response. Twenty-two patients received RT consolidation. RT consolidation was delivered using 3D-CRT, IMRT, or proton therapy. After a median (range) follow-up of 31.8 (2.2-55.1) months, the 3-y event-free survival rate and progression-free survival were 86.9% (69.5-94.7%) and 95% (76.7-99%), respectively. A novel combination of N + BV followed by ISRT was an effective second line therapy. This treatment regimen allowed patients to forgo high dose therapy and transplant in favor of consolidative radiotherapy using ISRT. Larger studies challenging the role of high dose therapy and transplant are needed for RRHL.

Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Center

Most small cell lung cancer cases present as Stage IV (M1) or extensive stage (ES-SCLC), which are defined as tumor extending outside the hemithorax without a tolerable radiation portal. The CREST trial demonstrated improved local control with a modest overall survival (OS) benefit at the 2-year secondary endpoint of 14% survival with consolidative thoracic radiotherapy (CTRT) compared to 3% without CTRT. Low toxicity rates were also observed. This study reports our institutional ES-SCLC experience for patients treated with CTRT. A retrospective review was conducted on ES-SCLC patients treated with CTRT at our institution between 2014 and 2019. CTRT was defined as ≥30 Gy of thoracic radiotherapy. OS and tolerability of treatment were assessed in this population. Chemotherapy details were also captured. OS rate was determined using the Kaplan-Meier method and the time from start of CTRT to last date of follow-up or death. CTRT tolerability was determined using incidence and grade of esophagitis and radiation pneumonitis as per CTCAE v5. We identified 100 ES-SCLC patients treated with any thoracic RT at our institute, of which 45 received thoracic RT for palliative intent or with <30 Gy. The remaining 55 patients received ≥30 Gy CTRT and were included for analysis. The median age was 65.1 years (range 46.6-86.9) and 36 (65%) were male. The median follow-up for this sample was 0.8 (range 0.03-4.2) years. Median chemotherapy cycles were 6 (range 1-6), most receiving ≥4 cycles (87%) and completing chemotherapy prior to CTRT initiation (91%) with a minority concurrently receiving chemotherapy and CTRT (9%). Platinum chemotherapy was the most common (96%) with 2 patients receiving etoposide alone (4%). The most common CTRT regimens were 30 Gy in 10 fractions (80%) followed by 40 Gy in 15 fractions (9%) and 45 Gy in 30 twice-daily fractions (7%). Most patients (67%) were treated with IMRT/VMAT technique, while the remaining (33%) patients were treated with 3DCRT. The median survival time was 1.3 years with 1- and 2-year OS of 57.2% (CI 44.0 - 74.3%) and 26.1% (CI 12.9 - 52.7%), respectively. CTRT was well tolerated with no grade 4+ toxicities. The most common toxicity was esophagitis with 21 patients (39%), of which 15 were G1 (28%) and 6 were G2 (11%). Radiation pneumonitis was present in 5 patients (9.2%) with 1 G1 (2%), 3 G2 (6%), and 1 G3 (2%) cases. Consolidative TRT for ES-SCLC in this institutional series was at least as good as the reported CREST outcome with modest acute toxicities in this cohort. Disease burden at diagnosis, chemotherapy response, patterns of failure, and subsequent therapies will be further investigated.

Differential Impact of Consolidative Thoracic Radiotherapy in Extensive-Stage Small Cell Lung Cancer Based on Systemic Therapy Type and Sex

Consolidative thoracic radiotherapy (cTRT) has been shown in phase III RCTs to improve overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer (ES-SCLC). This benefit was particularly pronounced in women compared to men in the 2015 CREST trial (hazard ratio [HR] 0.68 vs. 1.01, respectively). However, it is unknown whether similar findings would apply after chemoimmunotherapy (chemo-IO) became standard of care first-line treatment in 2018. In this analysis, we report national practice patterns and survival outcomes of cTRT versus no cTRT following chemo or chemo-IO, stratified by sex. Patients from the nationwide Flatiron Health de-identified electronic health record-derived database were included if they completed 4-6 cycles of first-line systemic therapy (platinum-doublet chemo or chemo-IO) for stage IV SCLC diagnosed between 2014 and 2021. Patients who progressed or started cTRT within 14 days or died within 90 days of completing systemic therapy were excluded to account for immortal time bias. We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent covariate and last date of chemo as index date. As a sensitivity analysis to address potential selection bias, we weighted the models by the inverse probability of receiving cTRT. All OS and PFS analyses were stratified by systemic therapy type and sex. A total of 1,227 patients were included (850 chemo, 377 chemo-IO). The proportion of patients who received cTRT increased from 11.7% in 2014 to 20.7% in 2017, and then decreased to 16.4% in 2021. There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. In adjusted analyses among women receiving chemo, cTRT was associated with superior OS (HR 0.68; 95% confidence interval [CI] 0.51-0.91) and PFS (HR 0.64; 95% CI 0.47-0.86) [Table 1]. There was a non-statistically significant trend towards improved OS (HR 0.57; 95% CI 0.32-1.02) and PFS (HR 0.59; 95% CI 0.34-1.02) among women receiving chemo-IO. No OS or PFS benefit with cTRT was observed in men receiving either chemo or chemo-IO. Findings were similar in weighted analyses. The survival impact of cTRT may be differentially impacted by sex, with female patients appearing more likely to benefit than male patients regardless of systemic therapy type. While the underpinnings of this association need to be elucidated, stratification by sex should be considered for RCTs studying cTRT in ES-SCLC.

Consolidative Radiotherapy for Residual PET-Avid Disease on Day +30 Post CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Up to30% of non-Hodgkin lymphoma (NHL) patients achieve a partial response (PR) to anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) on day +30. Most PR patients relapse and only 30% achieve spontaneous complete response (CR) without additional therapies. This study is the first to report on the role of consolidative radiotherapy (cRT) for PR PET-avid disease on day +30 post-CART in NHL. Aretrospective review across 3 institutions from 2018 to 2022 identified 60 patients with B-cell NHL who received CART and achieved PR (Deauville 4-5) with <5 PET-avid disease sites on day +30. Progression-free survival (PFS) was defined from CART infusion to any disease progression. Overall survival (OS) was defined from CART infusion to death. Local relapse-free survival (LRFS), calculated based on the total number of PR sites, was defined from CART infusion to local relapse (LR) in the PR site identified on day +30. cRT was defined as comprehensive (compRT) - treated all PR PET-avid sites - or focal (focRT). Followingday +30 PET scan, 45 PR patients were observed and 15 received cRT. Only one patient received consolidative systemic therapy and belonged to the cRT group. Prior to CART, bridging RT was given to 13 patients (9 in observation group and 4 in cRT group). There were no significant differences in the pre-CART and day +30 baseline characteristics, including the median size and SUVmax of the PR sites, between the two groups. However, the median number of PR sites on day +30 was higher in the cRT group (2 [range 1-3] vs 1 [range 1-3], p = 0.003). The median equivalent 2 Gy dose was 39.1 (Interquartile range 36.8-41) Gy, and the most common cRT regimen was 37.5 Gy in 15 fractions. The median follow-up was 21 months. Among the observed patients, 15 (33%) achieved spontaneous CR, and 27 (60%) experienced disease progression with all relapses involving the initial PR sites. Among patients who received cRT, 10 (67%) achieved CR, and 3 (20%) had disease progression with no relapses in the radiated PR sites. None of the 10 cRT patients achieving CR relapsed or required subsequent therapies. The 2-year PFS was 80% and 37% (p = 0.012) and the 2-year OS was 78% and 43% (p = 0.12) in the cRT and observation groups, respectively. Patients consolidated with compRT (n = 12) had superior 2-year PFS (92% vs 37%, p = 0.003) and 2-year OS (86% vs 43%, p = 0.048) compared to observed or focRT patients (n = 48). There were no grade 3+ RT-related toxicities. A total of 90 PR sites were identified; 64 were observed and 26 received cRT. Fourteen (22%) observed PR sites achieved spontaneous sustained CR and 42 (66%) experienced LR. Twenty-four (92%) PR sites consolidated with cRT achieved sustained CR and none experienced LR. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (p<0.001). NHL patients who achieve PR by PET to CART are at high risk of local progression. cRT for residual PET-avid disease on day +30 post-CART appears to alter the pattern of relapse and improve LRFS and PFS.

Circulating Tumor DNA for Early Risk Stratification of Oligometastatic Lung Cancer

Some patients with oligometastatic disease experience prolonged progression-free survival when treated with local consolidative radiotherapy (RT). Precisely identifying these patients remains challenging, however. We hypothesized that pre-RT liquid biopsy circulating tumor DNA (ctDNA) analysis could risk-stratify oligometastatic non-small-cell lung cancer (NSCLC) patients and enable earlier personalized selection for consolidative RT. A real-world multi-institutional cohort of 1,487 patients who were diagnosed with oligometastatic NSCLC was analyzed. Each patient underwent liquid biopsy ctDNA analysis using the Tempus xF assay (v2) at least once, for a total of 1,880 ctDNA assays. 20% of the cohort (n = 309) underwent RT after liquid biopsy was obtained and oligometastatic NSCLC was diagnosed by the treating physician. Each patient in the sub-cohort of 309 patients had oligometastatic disease, defined as metastatic disease present in 1-5 organ systems. Outcomes for overall survival (OS) and progression-free survival (PFS) were defined with respect to the initiation time of RT to minimize the risk of guarantee-time bias. ctDNA results were analyzed for variants using VarDict and characterized as pathogenic or likely pathogenic following ACMG/AMP guidelines for variant classification, as determined by SnpEff. Variants considered benign, likely benign, or having conflicting evidence were excluded from consideration. Overall survival was significantly worse in oligometastatic NSCLC patients with detectable ctDNA pre-RT, as compared to those without detectable ctDNA pre-RT, with a median OS of 16.8 months versus 25 months (p = 0.030, HR = 1.65, CI = 1.05-2.61). Similar findings were also observed for PFS, which was worse in patents with detectable ctDNA pre-RT, with a median PFS of 5.4 months versus 8.8 months (p = 0.004, HR = 1.57, CI = 1.15-2.13). ctDNA variant allele frequency (VAF) levels demonstrated significant risk correlations, with the maximum pre-RT ctDNA VAF associated with increased risk of both disease progression (p = 0.0084) and death (p = 0.0073). These findings were corroborated by multivariate Cox proportional hazards modeling for PFS (p = 0.02, PFS HR = 4.69, CI = 1.42-13.30) and OS (p = 0.004, HR = 5.66, CI = 1.64-16.85). Notably, multivariate Cox modeling did not show significant impacts of other clinical parameters, including gender, age at diagnosis, smoking status, and squamous histology. Additionally, the ctDNA mutational burden (the number of detectable pathogenic or likely pathogenic variants) was significantly associated with risk for both PFS (p = 0.003, HR = 1.16, CI = 1.06-1.26) and OS (p = 0.003, HR = 1.15, CI = 1.04-1.25) in a multivariate Cox regression model. These data suggest that liquid biopsy ctDNA detection represents a powerful pre-RT biomarker to risk-stratify oligometastatic NSCLC patients and potentially enable personalized decision-making for local consolidative RT.

Early Stereotactic Body Radiotherapy to the Primary Lung Lesion for Patients with Advanced NSCLC Treated with First-Line Systemic Therapy

Although adding consolidative stereotactic body radiotherapy (SBRT) to systemic therapy improves survival in advanced non-small cell lung cancer (NSCLC), the optimal timing of SBRT remains unclear. This study aimed to explore the clinical outcome of early and delayed SBRT to primary lung lesions of advanced NSCLC patients treated with first-line systemic therapy. We identified patients with advanced NSCLC who were suitable to receiveSBRT for the primary lung tumors after first-line systemic therapy. All eligible patients were treated with first-line systemic therapy and SBRT for their primary lung lesions. Early SBRT group was defined as patients who received SBRT for their primary lung tumor at the maximal response of systemic therapy. Delayed SBRT group was defined as patients who received SBRT after the occurrence of oligoprogression in primary lung tumor. The primary endpoints were progression-free survival 1 (PFS1, time from start of first-line systemic therapy to disease progression) and PFS2 (time from start of first-line systemic therapy to disease progression after SBRT). Overall survival (OS) and adverse effects (AEs) were secondary endpoints. A two-sided P value of 0.05 was considered statistically significant. All of the statistical analyses were performed with statistical software. A total of184 patients with advanced NSCLC treated with SBRT for primary tumors were screened, and 49 patients were eligible for enrollment in this study. The median age of the entire cohort was 66 years (range, 37-80 years), and 34 (69.4%) patients were male. Thirty-four patients (69.4%) were treated by target therapy and 15 (30.6%) were treated by chemotherapy and immunotherapy. Of the 49 eligible patients, 28(57.1%) received early SBRT to lung primary tumor and 21(42.9%) received delayed SBRT to lung primary tumor. The early SBRT group showed a significantly prolonged PFS1 as compared with the delayed SBRT group (mPFS1: 30 months vs. 8 months, P<0.001). The median PFS2 of the early SBRT group was longer than that of the delayed SBRT group, but the difference between the two groups did not achieve a statistical significance (mPFS2: 42 months vs. 23 months, P = 0.303). Median OS of both groups has not reached. No severe toxicities (≥grade 3) were observed in early SBRT group and only one patient in the delayed SBRT group experienced grade 3 radiation pneumonitis. Early SBRT to the primary lung lesion significantly improved PFS and is a new potentially effective and tolerable treatment option for patients with advanced NSCLC who had stable disease during first-line systemic therapy.

Survival Outcomes for Oligometastatic vs. Polymetastatic Extensive-Stage Small Cell Lung Cancer Following Consolidative Thoracic Radiotherapy

For patients with limited metastatic burden, metastasis-directed radiotherapy has been shown to be associated with improved OS for certain types of cancer. However, these prior trials did not include patients with ES-SCLC. It is not yet clear if patients with oligometastatic ES-SCLC have improved outcomes over polymetastatic ES-SCLC after cTRT. We identified patients treated with cTRT for ES-SCLC in 2013-2020 at a single institution. Oligometastatic disease was defined at the time of diagnosis as three or fewer organs with distant disease, and with each organ having three or fewer metastatic lesions. All other patients were considered polymetastatic. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare OS, progression-free survival (PFS), local recurrence-free survival (LRFS), and new metastasis-free survival (NMFS) between oligometastatic and polymetastatic ES-SCLC patients undergoing cTRT. Among 70 included patients, 36 were defined as oligometastatic. All patients received platinum-doublet chemotherapy and cT. Immunotherapy was given in 7 (19.4%) oligometastatic patients and 5 (14.7%) polymetastatic patients (p = 0.56). Median follow-up time was 38.2 months. Multivariable Cox regression analysis showed that oligometastatic disease (vs. polymetastatic disease) at diagnosis was associated with improved OS (hazard ratio [HR] 0.44, 95% CI 0.25-0.78, p = 0.005, 1-year OS 86.1% vs. 46.9%, 2-year OS 47.1% vs. 15.1%). PFS, LRFS, and NMFS were not significantly different between the cohorts. Among oligometastatic patients, pleural involvement (HR 2.44, 95% CI 1.02-5.83, p = 0.046) and lung involvement (HR 4.93, 95% CI 1.02-23.9, p = 0.047) were associated with inferior OS. Among the 26 of 36 (72.2%) oligometastatic patients with neither pleural nor bilateral lung involvement, 1-year OS was 88.5% and 2-year OS was 58.3%. We observed that oligometastatic ES-SCLC patients treated with cTRT (especially those without pleural or bilateral lung involvement) have superior OS than those with polymetastatic disease. We encourage enrollment on the NRG LU007/RAPTOR randomized trial to determine the impact of complete or incomplete consolidative RT to up to 5 sites in ES-SCLC, especially in those with oligometastatic disease.

Safety and Efficacy Analysis of Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Treated with SHR-1316 Plus Chemotherapy and Sequential Chest Radiotherapy as First-Line Therapy from a Phase II Trial

CAPSTONE-1, a phase 3 trial, showed that SHR-1316 (PD-L1 antibody) combined with standard first-line chemotherapy could prolong overall survival (OS) in patients (pts) with ES-SCLC. The CREST trial reported consolidative thoracic radiotherapy (TRT) of 30 Gy in 10 fractions provided a 10% 2-year OS benefit and more intensive TRT should be investigated in ES-SCLC. In the era of immunotherapy, the role of TRT also needs further exploration. Therefore, we designed this clinical trial to investigate the efficacy and safety of SHR-1316 plus first-line chemotherapy followed by TRT combined with SHR-1316. Key inclusion criteria were pts aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC, and an ECOG performance status of 0-1. Eligible pts would receive 4∼6 cycles of SHR-1316 (20mg/kg, D1, q3w) combined with EP/EC (etoposide, 100mg/m2, D1-5, q3w and cisplatin, 75mg/m², D1-3, q3w or carboplatin, AUC = 5, D1, q3w), followed by SHR-1316 combined with TRT (≥3 Gy*10 f or ≥2 Gy*25 f, involved-field irradiation), and then the maintenance therapy with SHR-1316 until disease progression or intolerable adverse events (AEs). The main endpoints included ORR, PFS and safety. From October 2020 to January 2023, 33 pts received SHR-1316 and sequential consolidative TRT. Among them, 19 pts received high-dose TRT (>3 Gy*10 f or ≥2 Gy*25 f) and 14 pts received low-dose TRT (≤3 Gy*10 f or<2 Gy*25 f). The median age was 62 (range: 38-73). Most pts were male (28, 84.8%), former smokers (22, 66.7%) with an ECOG performance status 1 (32, 97%). Ten (30.3%) pts were diagnosed with brain metastasis and 10 (30.3%) pts had liver metastasis at baseline. At the data cutoff date, 9 pts remained on treatment, the average number of treatment cycles was 9.2. 33 pts had at least one 1 post-treatment tumor assessment. The confirmed ORR and DCR were 90.9% (30/33) and 100% (33/33) in all pts, were 89.5% (17/19) and 100% (19/19) in high-dose TRT group, and were 92.9% (13/14) and 100% (14/14) in low-dose TRT group. The median PFS was 10.2(CI: 5.8∼14.7) months in all pts, was 7 (CI: 3.8∼10.2) months in high-dose TRT group and 10.4 (CI: 8.4∼12.3) months in low-dose TRT group. AEs occurred in 27 (81.8%) pts and grade 3 or 4 AEs occurred in 20 (60.6%) pts. The most common grade 3 or 4 AEs included neutropenia (15, 45.5%), leukopenia (8, 24.2%), lymphocytopenia (5, 15.2%), pneumonia (3, 9.1%), anemia (3, 9.1%) and thrombocytopenia (2, 6.1%). SHR-1316 plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. There is no significant difference between high-dose and low-dose TRT groups in terms of safety and efficacy according to current data.

30 Gy vs. 45 Gy Consolidative Thoracic Radiation (cTRT) for Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Multicenter, Randomized, Phase 3 Trial

Consolidative thoracic radiotherapy (cTRT) showed potential benefit to extensive stage small cell lung cancer (ES-SCLC). However, the optimum dose of cTRT is unknown. The purpose of this randomized trial was to compare the effect of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. This phase III, randomized trial was conducted in 12 public hospitals in China. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions or 45 Gy in 15 fractions cTRT. The primary outcome was 2-year overall survival (OS). Secondary outcomes included 2-year progression-free survival (PFS), 2-year local control (LC) and radiation treatment related toxicity. The primary objective was to detect an OS improvement in 45 Gy cTRT group at 2 years from 13% to 26% assuming a two-sided a = 0.05 and power of 85%, with a planned sample size of 186 patients. This trial was registered with Clinical Trials.gov, number NCT02675088. Between January 15, 2016, and September 20, 2022, 90 patients were randomly assigned either 30 Gy in 10 fractions (n = 50) or 45 Gy in 15 fractions (n = 40) cTRT group. Recruitment to the trial closed early due to slow accrual since first-line chemoimmunotherapy has become the new standard of care for ES-SCLC. The median age of patients was 58 years, 87.8% were male, 76.7% had a smoking history, 95.6% received IMRT, and 58.9% received prophylactic cranial irradiation. At a median follow-up of 39.9 months (IQR 27.2-59.2), there was no significant difference in the 2-year OS between the 45 Gy group and the 30 Gy group, at 43.4% (95% CI 29.3%-64.3%) and 40.0% (95% CI 27.9%-59.1%), respectively (log-rank p = 0.62; HR 1.13 [95% CI 0.69-1.84]). The 2-year PFS was 12.1% (95% CI 4.3%-33.8%) in the 45 Gy group and 9.0% (95% CI 3.2%-25.2%) in the 30 Gy group (log-rank p = 0.25, HR 0.76(95% CI [0.478-1.22]). There were also no significant differences in locoregional recurrence free survival (log-rank p = 0.75; HR 0.888 [95% CI 0.423-1.863]) and distant metastasis free survival (log-rank p = 0.95; HR 1.015 [95% CI 0.624-1.651]) between two groups. No grade 5 toxicity was observed in both groups. Patients treated with higher cTRT dose presented with increased incidence of grade 3+ radiation pneumonitis (10% vs 2%) and hematological toxicity (20% vs 12.5%). This randomized trial did not find a higher probability of survival improvement in patients with ES-SCLC receiving cTRT of 45 Gy in 15 fractions compared with 30 Gy in 10 fractions. In contrast, there was an increase in toxicity, especially radiation pneumonitis. Additional randomized studies investigating the role of cTRT in ES-SCLC after a response to chemoimmunotherapy are warranted.

Outcomes of Consolidative Thoracic Radiation within First-Line Chemoimmunotherapy in Extensive-Stage Small-Cell Lung Cancer: Results from a Single Cancer Center

Thoracic radiation (TRT) benefits local control undoubtedly and survival with some minor controversy in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing radiotherapy in the chemoradiotherapy era. However, whether TRT could further enhance the benefit of immune checkpoint inhibitors (ICIs) maintenance on outcomes in the immunotherapy era is still unclear. This study aims to investigate the role of consolidative TRT in ES-SCLC patients receiving first-line chemoimmunotherapy followed by immunotherapy maintenance. Outcomes of patients who were treated with first-line chemo-immunotherapy followed by ICIs maintenance for ES-SCLC were reviewed. Based on TRT or not, patients were allocated to TRT group or non-TRT group. Progression-free survival (PFS), overall survival (OS) and local-recurrence free survival (LRFS) were calculated by the Kaplan-Meier method and compared by log-rank test. A total of 100 patients with no progressive disease after 4 cycles of chemotherapy were retrospectively analyzed between January 2020 and December 2021 and were allocated into TRT group (n = 47) and non-TRT group (n = 53). The median follow-up time was 20.3 months. The median PFS and OS in TRT were 9.1 months and 21.8 months, versus 8.8 months (p = 0.93) and 24.3 months (p = 0.63), respectively, in non-TRT. ICIs agents consisted of Durvalumab (59.0%) and Atezolizumab (41.0%). The median dose of TRT is 50 Gy (IQR: 45 - 54), while the median interval time from chemotherapy completion to TRT was 31 days (IQR: 12 - 44.5). Only 10 (21.3%) patients terminated ICIs in the period of TRT. The rate of intrathoracic progression after the first-line therapy in TRT significantly decreased compared to that with non-TRT (20.0% versus 55.9%, p = 0.003). The median LRFS time in TRT was not reached, but significantly longer than 10.8 months in non-TRT (HR = 0.27, p < 0.01). Second-line chemotherapy significantly prolonged survival compared to that with chemo-free patients (mOS: 24.5 vs. 21.4 months, p = 0.026). The subgroup analysis showed a trend of patients with brain metastases benefit from TRT (21.8 versus 13.7 months, HR 0.61, p = 0.38) while liver metastases did not (13.3 versus 15.0 months, HR 1.80, p = 0.21). Of 47 patients with TRT, only 10.6% of patients experienced grade 3 radiation-induced pneumonitis, while no grade 4 or 5 adverse events occurred. None of patients experienced grade ≥ 3 treatment-related cardiac events. Consolidative TRT in the period of immunotherapy maintenance followed first-line chemo-immunotherapy did not prolong OS and PFS but increased LRFS in ES-SCLC.

Radiotherapy in Young, High-Risk Patients with Aggressive B-cell Lymphoma: Long-Term Results from the Open-Label, Randomized, Phase 3 R-MegaCHOEP Trial

The role of consolidative radiotherapy (RT) for young (< 60 years), high-risk patients with aggressive B-cell lymphoma is discussed. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantation compared to conventional R-CHOEP immunochemotherapy for patients up to 60 years1,2. Despite no prognostic difference between treatment arms even after 10-year follow-up, excellent long-term results were achieved. The presented work represents a detailed RT-analysis providing long-term data on efficacy and side-effects. The 10-year follow-up dataset of the R-MegaCHOEP trial with a median follow-up of 81.1 months (range 0.6-175.9 months) was used for this analysis. Indications for consolidative RT were extralymphatic involvement or bulky disease (maximum diameter ≥ 7.5 cm). Additionally, RT could be administered because of insufficient response at end of therapy as evaluated by CT scan. Overall, 261 patients were analyzed, 120 of whom underwent RT. Patients with RT were predominantly male (65.8 %), had an age-adjusted IPI of 2 (75 %), an elevated LDH (96.7 %) and showed an ECOG-Score of 0-1 (65 %). Bulky disease was present in 103/120 patients in the RT-arm with a bulk size of 7.5-20.0 cm (median: 11 cm) and was located predominantly in the mediastinal (44), paraaortal (17) and mesenteric (13) regions. The most frequently irradiated regions were the mediastinal (50), paraaortic (27) and mesenteric (15) regions. Median RT dose was 36 Gray in median fractions of 1.8 Gray. Toxicities were generally mild to moderate with 24 and 8 grade 3 and 4 toxicities reported during RT. During long-term follow-up, 23 secondary malignancies occurred, with RT being no significant contributing risk factor (p = 0.188). Analysis of the overall study population showed that patients with RT had an improved event-free survival (EFS; 63.9 % vs. 46.0 %; p<0.001) and progression-free survival (PFS; 67.2 % vs. 54.1 %; p = 0.025) but not overall survival (OS; 72.8 % vs. 65.9 %; p = 0.132) in comparison to non-irradiated patients after 10 years. Considering only those patients with RT after a complete remission/unconfirmed complete remission after systemic therapy, a significantly improved EFS (66.4 % vs. 46.0 %; p = 0.006), but not PFS and OS, was shown (PFS: p = 0.054; OS: p = 0.222). For patients with bulky disease, RT resulted in a significantly better outcome (10-year EFS: 64.4 % vs. 34.5 %; p<0.001; 10-year PFS: 68.3 % vs. 47.4 %; p = 0.003; 10-year OS: 71.5 % vs. 59.4 %; p = 0.011), when compared to patients without RT. For patients with extralymphatic involvement, RT improved EFS (10-year EFS: 61.7 % vs. 51.1 %; p = 0.017), but not PFS or OS (PFS: p = 0.068; OS: p = 0.305). RT improved outcome in young, high-risk patients with aggressive B-cell lymphoma and bulky disease. NCT00129090. 1 Lancet Oncol 2012;13(12):1250-1259. 2 Lancet Haematol 2021;8(4):e267-e277.

Radiotherapy Effect on Long-Term Net Survival Benefit for Early-Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era

It is controversial whether to add consolidative radiotherapy (RT) after chemoimmunotherapy in the first-line treatment for diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the long-term net survival benefit of RT for early-stage DLBCL in the rituximab era. The data of 10,841 adult patients with early-stage DLBCL from the Surveillance, Epidemiology, and End Results (SEER) database between 2002 and 2015 were extracted and analyzed. The patients had received combined modality treatment (CMT, chemotherapy plus RT) or chemotherapy alone. Linear regression analysis was performed for RT utilization by year of diagnosis. Competing risk analysis was used to evaluate the cumulative incidence of mortality according to the cause of death. Inverse probability of treatment weighting (IPTW) was used to balance the distribution of covariates between treatment arms. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were performed to estimate the net survival benefit of RT by controlling for background mortality. Linear regression revealed that the slope of the best-fit line for RT utilization over time was negative between 2002 and 2015 (m = -0.006, P = 0.003). A total of 4,648 deaths were recorded among 10,841 patients; 55.6% were lymphoma-related death (LRD), and 44.4% were attributed to other causes. Patients initially treated with CMT had a lower cumulative incidence of LRD than chemotherapy alone (HR 0.63, 95% CI: 0.57-0.69; P < 0.001). The 10-year overall survival (OS) rate of 66.1%, RS rate of 85.0%, and SMR of 1.71 achieved with CMT were significantly better than chemotherapy alone (OS, 53.0%; RS, 69.8%; SMR, 2.62; P < 0.001). By IPTW and multivariable analysis, the addition of RT remained associated with better OS (HR 0.67, 95% CI: 0.62-0.71; P < 0.001) and RS (HR 0.69, 95% CI: 0.65-0.74; P < 0.001). RT was associated with better long-term net survival in patients with early-stage DLBCL in the rituximab era.

Quality Analysis of Radiation Therapy for Hodgkin Lymphoma in the HD 16/17 Trials: A Final Report By the Reference Radiation Oncology Panel of the German Hodgkin Study Group

The HD 16 and 17 trials by the German Hodgkin Study Group (GHSG) have evaluated the use of consolidative radiotherapy (RT) in early-favorable and -unfavorable stage Hodgkin lymphoma (HL), respectively (1, 2). Quality of RT planning and execution is pivotal for treatment outcome in HL with protocol violations jeopardizing prognosis (3). Consequently, the present work aims at a decisive analysis of quality and dosimetry in the modern era. Random samples of 100 involved-field RT (IFRT) plans in HD16 and 176 plans in HD17 (134 involved-node RT (INRT) and 42 IFRT) were selected for analysis. Evaluation was performed systematically by the reference radiation oncology panel using pre-chemotherapy imaging, recommendation by the reference radiation oncology and RT planning imaging and graded as "correct", "minor" or "major deviation", respectively. RT doses to the target volume and organs at risks (OAR) were analyzed using dose-volume histograms. Median RT doses were 20 Gy (19.8 Gy-21.6 Gy) in HD16 and 30 Gy in HD17 (IFRT: 18-30.6 Gy, INRT: 14 Gy-40 Gy). Overall, 84.0%, 69.0%, and 76.1% of RT series in HD16, the IFRT-group of HD17 and the INRT-group of HD17, respectively, were planned correctly. The main reason for major deviation was an insufficient coverage of an involved region (11 %-14.3 %). There was no significant difference in quality between IFRT and INRT in HD17 (p = 0.418 for any deviations; p = 0.466 for major deviations). In comparison to previous GHSG studies in the respective stages, a significant increase in correct RT-series (p<0.001) and decrease in major deviations (p<0.001) occurred. However, doses to OAR varied individually with median values of 4.3 Gy (0.2 Gy-9.2 Gy), 4.7 Gy (0.2 Gy-15.2 Gy) and 3.8 Gy (0.0 Gy-16.0 Gy) for mean doses to the right lung, left lung and heart in HD16, respectively. Correspondingly, values were 9.8 Gy (0.3 Gy-20.0 Gy), 10.5 Gy (0.2 Gy-26.5 Gy) and 13.1 Gy (0.5 Gy-30.4 Gy) for mean doses to the right lung, left lung and heart in HD17, respectively. The size of the planning target volume decreased significantly with INRT compared to IFRT (median values: 1163.1 ml vs. 1464.3 ml; p = 0.043). However, only some OAR-parameters (V25 of the right and left lung, respectively, thyroid and spinal cord) showed significant differences between INRT and IFRT in HD17. The use of intensity-modulated techniques in HD 17 resulted in an increase in V5 and V10 of the lungs with a concomitant decrease in V20-V30. Quality of RT in the planning and treatment of HL has improved significantly with the latest GHSG study generation. Future analyses will focus on a further individualization of treatment fields.

Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer

Local consolidative radiotherapy (LCT) for oligometastatic disease is a promising paradigm improving outcomes for various malignancies but has been underexplored for metastatic thyroid cancer. We hypothesize that LCT to distant sites with definitive RT doses can yield favorable outcomes and defer systemic therapy escalation for these patients. We reviewed 96 thyroid cancer patients who received 175 LCT courses from 2010-2022 to 228 metastatic sites, including: thorax (45%), bone (40%), brain (6%), head/neck (5%), and abdomen (3%). Common prescriptions were 50-55Gy/4-5fxs or 56-70Gy/8-10fxs for lung; 52.5-60Gy/15fxs for mediastinum; and 18-24Gy/1fx or 27-30Gy/3fxs for bone. RECIST v1.1 and CTCAE v5.0 were used to define progression and toxicities, respectively. Outcomes were evaluated via Kaplan-Meier and associations examined via Cox proportional hazards modeling. Median age was 63 years (range: 26-92), with 62 oligometastatic cases (total 1-5 sites) and 34 oligoprogressive (with 1-5 growing sites). Primary disease was controlled in all patients, with 39% receiving post-op RT and 66% prior RAI. Histologies included papillary (40%), anaplastic (25%), follicular (12%), medullary (9%), Hurthle (7%), and poorly-differentiated (7%). Median time from initial diagnosis to LCT was 3 yrs (IQR 1-8), and median follow-up from 1st LCT was 21 mos (IQR 9-51). Patients received an average 2 LCT courses (range 1-8) treating 1-4 sites. Median survival (OS) from 1st LCT was 9 yrs (95% CI = 5-14). On multivariable analysis (MVA), worse OS was associated with anaplastic histology (HR 4.6, p<.01), but longer OS was associated with prior RAI (HR 0.33, p = .02) and oligometastatic disease (HR 0.3, p = .01). For anaplastic histology, median OS was 1.2 years vs. 9.3 years for non-anaplastic; 3-yr OS was 36% vs. 88% (log-rank, p<.01). Five-year OS for oligometastatic cases was 75% vs 53% for oligoprogressive (log-rank, p = .04). Median progression free survival (PFS) from 1st LCT was 15.5 mos (95% C I = 11-20). On MVA for all LCT courses, time to any progression (TTP) was negatively associated with anaplastic histology (HR 1.7, p = .02) and 2nd or higher LCT course (HR 1.45, p = .05), but favorably associated with thoracic site (HR 0.49, p<.01). Following later LCT courses, median TTP was 11 mos vs 17 mos for initial LCT course (log-rank, p = .03). After LCT to lung/chest, TTP was 18.6 mos vs 9.5 mos for non-thoracic sites (log-rank, p<.01). Only 6% of failures occurred at previously treated lesions. Most LCT courses (67%) were without ongoing chemotherapy, while 25% entailed continuing the same regimen and 9% had planned treatment post-RT. There were 2 Grade 3 toxicities (pneumonitis and esophagitis) and no Grade 4-5 events. With high local control rates and minimal toxicity, LCT can be a feasible strategy to defer systemic therapy escalation for oligometastatic and oligoprogressive thyroid cancer.

Role and Modality of Combining Radiotherapy with Immunotherapy in Stage III-IV Unresectable Small Cell Lung Cancer

The combination of radiotherapy and immunotherapy was rarely reported in the management of small cell lung cancer (SCLC). We retrospectively assessed the role and modality of this combination in Stage III-IV unresectable SCLC. Patients with stage III and IV SCLC were enrolled according to AJCC 8th edition. Both efficacy and safety of immunotherapy combined with radiotherapy were evaluated. Thereinto, patients received first-line chemo-immunotherapy and sequential thoracic consolidation radiotherapy (TCRT) were further evaluated. Survival and descriptive analyses were performed. Between January 1, 2019 and December 31, 2021, 51 patients were included in our analysis. Median follow-up was 28.0 months (95% CI 22.8-33.2). Patients received radiotherapy in treatment course had a prolonged 2-year overall survival (OS). And in the first-line immunotherapy cohort of 27 patients, the addition of TCRT significantly improved 2y-OS (72.22% vs. 13.89%, p = 0.0048), 2y-locoregional recurrence free survival (LRRFS) (90.00% vs 48.00%, p = 0.011), and 2y-distance progression free survival (DPFS) (66.67% vs. 16.67%, p = 0.039). Subgroup analyses showed that TCRT rendered superior outcomes regardless of brain metastases. Dose-escalation (45 Gy/15f) and earlier radiotherapy seemed to improve the benefit. Of 70.37% (19/27) patients experienced disease progression in the TCRT evaluation cohort, 63.16% (12/19) patients failed in brain. A tendency toward better OS and superior brain metastases free survival (BMFS) were observed after receiving prophylactic cranial irradiation (PCI). Finally, the most common grade 2 or higher toxic effects were pneumonitis in all patients (11.76% of immune-related vs. 7.84% of radiation related). Earlier addition of TCRT to immunotherapy could significantly improve survival and extracranial control for stage IIIA-IVB unresectable SCLC patients, with no increased risk of adverse events. In the era of immunotherapy, PCI may still be a recommended strategy. Further investigation is warranted.

Decreased lymphoma-related deaths and improved long-term relative survival with radiotherapy for early-stage diffuse large B-cell lymphoma in the rituximab era

BackgroundWe aimed to investigate the incidence of lymphoma-related death (LRD) and the long-term net survival benefit of radiotherapy (RT) for early-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Methods10,841 adults diagnosed with early-stage DLBCL between 2002–2015 were retrospectively analyzed using data from the Surveillance, Epidemiology, and End Results database. Primary therapy was categorized into combined-modality treatment (CMT, n = 3,631) and chemotherapy alone (n = 7,210). Competing risk analysis was used to evaluate the cumulative incidence of mortality. Inverse probability of treatment weighting (IPTW) was used to balance groups. The net survival benefit of RT was estimated through relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression, while controlling for background mortality. ResultsPatients initially treated with CMT had a lower cumulative incidence of LRD compared to those who received chemotherapy alone (HR 0.63, 95%CI: 0.57–0.69; P < 0.001). The 10-year overall survival (OS), RS, and SMR for CMT were 66.1%, 85.0%, and 1.71 respectively, which were significantly better than those for chemotherapy alone (53.0%; 69.8%; 2.62; all P < 0.001). IPTW and multivariable analysis revealed that the addition of RT led to better OS (HR 0.67, 95%CI: 0.62–0.71; P < 0.001) and RS (HR 0.69, 95%CI: 0.65–0.74; P < 0.001). Moreover, compared with chemotherapy alone, the benefit of OS and RS for CMT increased over time within 10 years of diagnosis. ConclusionRT reduced LRD and improved the long-term net survival in early-stage DLBCL in the rituximab era. Further prospective studies are warranted to assess the specific patient population that would benefit the most from consolidative RT in early-stage DLBCL.

Primary Prevention of Neutropenia by Empegfilgrastim in Patients with Advanced Stages of Classical Hodgkin Lymphoma Treated with Intensive First-Line Chemotherapy with a Modified 6-Cycle Program EACODD-14 Under the Protocol “LKh-Rossiya-1”

Aim. To assess the efficacy of a long-acting form of the granulocyte colony-stimulating factor (G-CSF) empegfilgrastim in primary prevention of neutropenia in patients with advanced stages of classical Hodgkin lymphoma (cHL) who received intensive chemotherapy with reduced inter-cycle interval under the protocol “LKh-Rossiya-1”.&#x0D; Materials &amp; Methods. The study enrolled 35 patients with newly diagnosed cHL. All patients had advanced stages (IIB X/Е and III/IV) of the disease. They were treated at the NI Pirogov National Medical and Surgical Center from March 2013 to August 2022. The primary prevention of neutropenia by long-acting G-CSF (empegfilgrastim) was administered to 21 patients under the protocol “LKh-Rossiya-1”. They received 6 chemotherapy cycles of modified EACODD-14, in total 126 cycles. The control group consisted of 14 patients who received 6 ЕАСОРР-14 chemotherapy cycles (in total 84 cycles) with dacarbazine as substitution for procarbazine. In the control group, the primary prevention of neutropenia was carried out using discrete G-CSF (filgrastim). The median (range) follow-up in the main (n = 21) and control (n = 14) groups was 18 (5–36) and 39 (29–116) months, respectively. The treatment efficacy was assessed based on PET-CT in 31 patients and on CT in 4 patients.&#x0D; Results. By the end of chemotherapy, complete metabolic response was achieved in 28 (80 %) out of 35 patients (95 % in the EACODD-14 and 73 % in ЕАСОРР-14 groups). In 6 (17 %) patients, partial remission was confirmed only by CT scan, and in 1 (3 %) patient, PET/CT showed stabilization. After consolidation radiotherapy, complete remission was reported in all 35 patients. Both groups received the full chemotherapy program per protocol. Without a violation of G-CSF regimen, the EACODD-14 group received 121 (96 %) cycles out of those 126 planned, whereas the ЕАСОРР-14 group received all 84 cycles per protocol. Full implementation of 107 (88.4 %) cycles in the first group and 24 (29 %) cycles in the second group was achieved in 12 (57 %) and 5 (36 %) patients, respectively (p &lt; 0.001). Neutropenia grade 4 was more often identified in filgrastim than in empegfilgrastim recipients (57 % vs. 19 %; p &lt; 0.05) and in a larger number of cycles (15 % vs. 3 %; p &lt; 0.01). The rate of infection episodes in the ЕАСОРР-14 group was higher (50 % vs. 28 %) and in more cycles (15 % vs. 5 %; p &lt; 0.05). Due to the use of long-acting G-CSF (empegfilgrastim) the number of inpatient days could be reduced from 9 to 5.&#x0D; Conclusion. The results of this study demonstrate the advantage of long-acting G-CSF (empegfilgrastim) as compared with its discrete form (filgrastim) in intensified programs with a reduced inter-cycle interval and high risk of febrile neutropenia (EACODD-14 and EACOРР-14). The use of empegfilgrastim allowed to administer three times as many chemotherapy cycles adhering to the principle of dose intensity in a larger number of patients with advanced cHL stages.

215 Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Centre

215 Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Centre