Palliative Thoracic Radiotherapy Research Articles

Sex Differences in Presentation, Treatment, and Survival in Patients Receiving Palliative (Chemo)Radiotherapy for Non-Small Cell Lung Cancer.

The aim of this study was to analyze sex differences in a real-world cohort of patients who received palliative thoracic radiotherapy or chemoradiotherapy for non-small cell lung cancer. Retrospectively, baseline, treatment, toxicity, and survival data from a single institution were analyzed. The study included 181 patients (82 females, 99 males). Despite borderline significant differences in disease presentation (T and N stage), final assignment to stage II, III or IV was similar. The same was true for target volume size. Neither radiotherapy parameters nor systemic treatment approaches were significantly different. Toxicity profiles and survival were similar too. Less than 1 out of 3 patients experienced high-grade toxicity, largely esophagitis. Median survival was 8.1 (males) versus 7.8 months (females) and the corresponding 2-year survival rates were 16 and 15%, respectively (p=0.78). Relevant sex differences were not observed in this study of common radiotherapy regimes such as 10 fractions of 3 Gy or 15 fractions of 2.8 Gy, the latter often combined with carboplatin/vinorelbine chemotherapy.

EP09.01-05 Is Palliative Thoracic Radiation Beneficial in Stage IV Non-small Cell Lung Cancer (NSCLC) In the Era of Modern Systemic Therapy?

EP09.01-05 Is Palliative Thoracic Radiation Beneficial in Stage IV Non-small Cell Lung Cancer (NSCLC) In the Era of Modern Systemic Therapy?

Pneumonitis after Palliative Thoracic Radiotherapy +/- Immunotherapy: A Retrospective Propensity-Matched Cohort Study

Patients (pts) with advanced lung cancer often receive combined palliative thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICI). There are limited data assessing the toxicities of combined ICI-RT in this setting. We sought to compare the rates of clinically significant pneumonitis among pts with lung cancer receiving palliative thoracic RT with or without recent or concomitant ICI. We hypothesized there would be a higher rate of grade 2+ pneumonitis among RT pts who received recent or concomitant ICI compared to those who did not. We retrospectively identified consecutive pts with advanced/recurrent lung cancer from a tertiary academic center who received palliative thoracic RT with recent (defined as within 95 days of RT start) or concomitant ICI (ICI-RT group) between January 2014 and February 2020. Pts were propensity matched in a 1:1 manner (by age, sex, ECOG, RT modality, and RT dose) to lung cancer pts who received palliative thoracic RT without any history of ICI receipt (RT-only group). The presence and grade (CTCAE v5.0) of pneumonitis were independently assessed by two investigators. The primary endpoint was grade 2+ pneumonitis, estimated using the cumulative incidence function and compared between the ICI-RT and RT-only groups using Gray's test. The secondary endpoint was overall survival, estimated using the Kaplan-Meier method and compared between groups using the log-rank test. A total of 146 pts were included in the study (73 in each group). There were no statistically significant differences between the ICI-RT and RT-only groups with respect to age (median 67.7 vs. 67.6, p = 0.97), sex (52% vs. 52% female, p = 1.00), pre-treatment ECOG 0-1 (74% vs 75%, p = 0.85), or biologically effective dose greater than 45 (48% vs. 48%, p = 1.00). The most common RT regimens were 30 Gy in 10 fractions (33 pts, 23%) and 20 Gy in 5 fractions (18 patients, 12%). A plurality of cases utilized 3DCRT (67 pts, 46%). In the ICI-RT group, the median time from last dose of ICI to the start of palliative RT was 16 days; three pts in this group-initiated ICI while receiving RT treatment. The most common ICI was pembrolizumab (36 pts, 49%). A total of eleven grade 2+ pneumonitis events (nine grade 2 and two grade 3 events) were observed. The ICI-RT group had a higher cumulative incidence of grade 2+ pneumonitis compared with the RT-only group (1-year rate, 12.3% vs. 2.7%, p = 0.029); grade 3 pneumonitis occurred in 1/73 (1.4%) in each group. There was no difference in overall survival between groups (median 239 vs. 218 days, p = 0.76). In pts with advanced lung cancer treated with palliative thoracic RT, recent or concomitant ICI use was associated with a higher cumulative incidence of grade 2+ pneumonitis. However, the incidence of grade 3+ pneumonitis was low (1.4%) regardless of ICI receipt.

Palliative Radiotherapy for Non-metastatic Non-small-cell Lung Cancer: Impact of Blood Test Results on Survival.

Non-small-cell lung cancer (NSCLC) not amenable to curative treatment can be managed with palliative thoracic radiation or chemoradiation, however, with variable success. This study evaluated the prognostic impact of the LabBM score [serum lactate dehydrogenase (LDH), C-reactive protein, albumin, hemoglobin, platelets] in 56 patients who were scheduled to receive at least 10 fractions of 3 Gy. Uni- and multivariate analyses of prognostic factors for overall survival were employed in a retrospective single-institution study of stage II and III NSCLC. The first multivariate analysis showed that hospitalization in the month before radiotherapy (p<0.001), concomitant chemoradiotherapy (p=0.03), and LabBM point sum (p=0.09) were the leading predictors of survival. A second model with individual blood tests rather than the sum score suggested that concomitant chemoradiotherapy (p=0.002), hemoglobin (p=0.01), LDH (p=0.04), and hospitalization before radiotherapy (p=0.08) played important roles. Surprisingly long survival was seen in patients without prior hospitalization who received concomitant chemoradiotherapy and had favorable LabBM score (0-1 points): median 24 months, 5-year rate 46%. Blood biomarkers provide relevant prognostic information. The LabBM score has 1) previously been validated in patients with brain metastases and 2) demonstrated encouraging results in a cohort irradiated for different palliative non-brain indications, e.g., bone metastases. It might be helpful in predicting survival in patients with non-metastatic cancer, e.g., NSCLC stage II and III.

Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE)

Palliative thoracic radiotherapy (RT) can alleviate local symptoms associated with advanced non-small cell lung cancer (NSCLC), but esophagitis is a common treatment-related adverse event. Whether esophageal-sparing intensity-modulated RT (ES-IMRT) achieves a clinically relevant reduction in esophageal symptoms remains unclear. To examine whether ES-IMRT achieves a clinically relevant reduction in esophageal symptoms compared with standard RT. Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE) is a multicenter phase 3 randomized clinical trial that enrolled patients between June 24, 2016, and March 6, 2019. Data analysis was conducted from January 23, 2020, to October 22, 2021. Patients had up to 1 year of follow-up. Ninety patients at 6 tertiary academic cancer centers who had stage III/IV NSCLC and were eligible for palliative thoracic RT (20 Gy in 5 fractions or 30 Gy in 10 fractions) were included. Patients were randomized (1:1) to standard RT (control arm) or ES-IMRT. Target coverage was compromised to ensure the maximum esophagus dose was no more than 80% of the RT prescription dose. The primary outcome was esophageal quality of life (QOL) 2 weeks post-RT, measured by the esophageal cancer subscale (ECS) of the Functional Assessment of Cancer Therapy: Esophagus questionnaire. Higher esophageal cancer subscale scores correspond with improved QOL, with a 2- to 3-point change considered clinically meaningful. Secondary outcomes included overall survival, toxic events, and other QOL metrics. Intention-to-treat analysis was used. Between June 24, 2016, and March 6, 2019, 90 patients were randomized to standard RT or ES-IMRT (median age at randomization, 72.0 years [IQR, 65.6-80.3]; 50 [56%] were female). Thirty-six patients (40%) received 20 Gy and 54 (60%) received 30 Gy. For the primary end point, the mean (SD) 2-week ECS score was 50.5 (10.2) in the control arm (95% CI, 47.2-53.8) and 54.3 (7.6) in the ES-IMRT arm (95% CI, 51.9-56.7) (P = .06). Symptomatic RT-associated esophagitis occurred in 24% (n = 11) of patients in the control arm vs 2% (n = 1) in the ES-IMRT arm (P = .002). In a post hoc subgroup analysis based on the stratification factor, reduction in esophagitis was most evident in patients receiving 30 Gy (30% [n = 8] vs 0%; P = .004). Overall survival was similar with standard RT (median, 8.6; 95% CI, 5.7-15.6 months) and ES-IMRT (median, 8.7; 95% CI, 5.1-10.2 months) (P = .62). In this phase 3 randomized clinical trial, ES-IMRT did not significantly improve esophageal QOL but significantly reduced the incidence of symptomatic esophagitis. Because post hoc analysis found that reduced esophagitis was most evident in patients receiving 30 Gy of RT, these findings suggest that ES-IMRT may be most beneficial when the prescription dose is higher (30 Gy). ClinicalTrials.gov Identifier: NCT02752126.

126 - Survival outcomes of palliative thoracic radiotherapy in non-small cell lung cancer

126 - Survival outcomes of palliative thoracic radiotherapy in non-small cell lung cancer

Combination of Palliative Thoracic Radiotherapy With Bevacizumab for Stage IV Nonsquamous NSCLC: Is There Any Impact of Time Interval on Survival?

Background:The time interval between palliative thoracic radiotherapy and bevacizumab treatment strongly influences the frequency of adverse events (AEs) when both are concurrently applied to patients with advanced lung cancer. Herein, we aimed to elucidate the optimal time interval between the treatments in these patients.Methods:The medical records of patients with stage IV nonsquamous non–small-cell lung cancer (NSCLC) without epidermal growth factor receptor and anaplastic lymphoma kinase alteration who underwent palliative thoracic radiotherapy and bevacizumab treatment from January 2008 to January 2020 were collected and analyzed. Patients were divided into 2 groups based on the time interval between treatments: <3 weeks (⩽3W group) and >3 weeks (>3W group). The progression-free survival (PFS) and overall survival (OS) for the time intervals were evaluated using the Kaplan-Meier method and Cox proportional hazard models. Adverse events were assessed by the fifth version of the Common Terminology Criteria for Adverse Events.Results:In total, 72 patients with stage IV NSCLC (⩽3W group, 37 patients; >3W group, 35 patients) who concurrently or sequentially received palliative thoracic radiotherapy and bevacizumab treatment were included in this study. In the >3W and ⩽3W groups, the median PFS (8 vs 6 months, respectively) and OS (15 vs 12 months, respectively) differed significantly. Multivariate analyses findings revealed significantly shorter OS in the latter group. In addition, the frequency of most AEs was marginally higher in the latter group (P > .05).Conclusions:The time interval between palliative thoracic radiotherapy and bevacizumab treatment that offers optimal safety is >3 weeks.

Clinical profile and initial treatment of non-small cell lung cancer: a retrospective cohort study at the Uganda Cancer Institute.

Lung cancer is a major global public health burden constituting 11.6% of all new cancer diagnoses and 18.4% of all cancer-related mortality. To describe the clinical profile and initial treatment of non-small cell lung cancer in Uganda. We reviewed charts of a cohort of patients with a histologically confirmed diagnosis of non-small cell lung cancer, treated between January 2013 and November 2015 at the Uganda Cancer Institute. A total of 74 patients met the inclusion criteria. The median age was 56 years (IQR 47-70), with 16.2% below the age 45 years, and 51% were female. Only 10 percent were active smokers and the most frequent histological subtype was adenocarcinoma (71%). The majority (91.9%) had stage IV disease at diagnosis and frequent metastases to contralateral lung, liver, and bones. Twenty-seven (27) patients received platinum-based chemotherapy, while 27 patients received erlotinib, and only 4 patients received palliative thoracic radiotherapy. The median survival time was 12.4 months, and the overall response rate was 32.7%. There was no survival difference by type of systemic treatment, and on multivariate analysis, poor performance status was predictive of adverse outcomes (p < 0.001). Patients with non-small cell lung cancer in Uganda frequently presented with late-stage disease at diagnosis. The majority of patients were female, never-smokers, and had predominantly adenocarcinoma subtype.

Identification of Clinical Predictors of Benefit of Palliative Thoracic Radiotherapy

Palliative thoracic radiotherapy (PTRT) is frequently utilized for relief of pain, obstruction and hemoptysis from lung and bronchial primary tumors and metastatic disease. Historically, the prognosis for these patients has been dismal with radiotherapy (RT) often serving as a last line of therapy. However, with continued advancements in systemic therapies for non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and other malignancies, PTRT may provide increased benefit both in relief of symptoms and prolongation of life for select patients. In this study, we sought to determine clinical predictors of benefit of PTRT in a contemporary cohort of patients with the goal of aiding in appropriate patient selection for escalation or de-escalation of RT in patients with locally advanced or metastatic disease.Patients treated with standard palliative courses of RT, including 8 Gy/1 fx, 20 Gy/5 fx, and 30 Gy/10 fx, to the thoracic cavity between 2014 and 2020 were identified. Clinical information was collected, including age, ECOG PS, histology, stage, presence of brain metastases, presence of lung collapse, lines of previous systemic therapy, neutrophil-lymphocyte ratio (NLR), mutational status, and survival outcomes. Kaplan-Meier analyses were used for survival and sensitivity analyses. Cox regression was performed for multivariate analysis.161 evaluable patients were identified who received PTRT for various indications including dyspnea, SVC syndrome, hemoptysis, pain and obstruction/lung collapse. A majority of patients (61%) had a diagnosis of NSCLC, although SCLC (10%) and other histologies (29%) were also included. 94% of patients were metastatic at the time of receipt of PTRT. Multivariate analysis identified female sex, multi-fraction regimens, better baseline ECOG performance status, presence of an actionable mutation, absence of brain mets, and non-lung histologies as positive predictors of survival following PTRT (P < 0.05). Other factors including age, number of lines of systemic therapy and NLR were not identified as independent predictors in this cohort in either multivariate or univariate analyses. Notably, 14 patients failed to complete prescribed therapy all of whom had ECOG PS of 2 or greater at start of RT.Patients with symptomatic lung disease derive differential benefit from PTRT with ECOG 0-1, absence of brain mets and presence of actionable mutations important clinical predictors of longer-term survival following treatment. Single fraction courses should be strongly considered for poor PS patients who may derive less significant survival benefit from PTRT and are at higher risk for early treatment discontinuation.

Survival and Local Control Outcomes Following Palliative Radiation for Malignant Airway Obstruction

Palliative radiation may be beneficial for patients with metastatic or locally advanced disease causing malignant airway obstruction (MAO). However, the subset of patients most likely to benefit from palliative airway radiation is unknown. In this study, we seek to report local control and survival outcomes for patients treated with palliative radiation for MAO and provide prognostic factors for improved overall survival.An IRB approved single institution retrospective review of patients treated with palliative thoracic radiation for MAO from 2008-2016 was undertaken. The primary study endpoint was overall survival (OS) and secondary endpoints included local response and airway specific progression free survival. Kaplan-Meier survival, and Cox proportional hazards regression analyses were performed to identify factors associated with OS. Variables with clinical and univariate significance were modelled using multivariate logistic regression analysis.Palliative radiation for MAO was identified for 237 patients (median age of 63.8 yrs). 88.6% of patients were treated for primary lung cancer and 41.6% of those patients had adenocarcinoma histology. At time of analysis, 78.5% patients had died. Median follow-up was 2 months. Out of 116 patients with imaging follow-up: 31.0% had airway specific progression, 68.9% had complete or partial response at last follow up. For those patients with palliative tumor response, median time to progression was 5.0 (Range 1.1-17.8) months. Kaplan-Meier estimate of median overall survival following start of radiation therapy was 5.0 (95% CI 3.8-5.8) months. In multivariable analyses, there was a marginally increased hazard ratio for patients who had dyspnea at rest HR 2.09 (95% CI 0.78-5.62), oxygen requirement at presentation HR 1.28 (95% CI 0.81-2.01), and higher ECOG level 2-4 HR 1.21 (95% CI 0.81-1.80). Conversely, squamous cell histology and treatment with BED10 greater than or equal to 39 (equivalent to the commonly used 30Gy in 10 fraction regimen) were significantly predictive of improved OS, HR 0.56 (95% CI 0.32-0.97) and HR 0.42 (95% CI 0.28-0.64) respectively.To our knowledge, this analysis is the largest collection of patients receiving palliative thoracic radiotherapy for MAO. These data show that MAO is a poor prognostic feature for survival, but treatment responses are seen. Increased BED delivered and squamous cell carcinoma, a radiosensitive tumor histology, were associated with improved survival. These results may help to inform optimized patient selection for and outcomes of patients with MAO receiving palliative RT.

1235P Comparative study between two 17-gray fractions versus thirteen 39-gray fractions palliative thoracic radiotherapy in advanced non-small cell lung carcinoma

In an effort to improve symptom palliation, palliative thoracic radiotherapy (TRT) has been integrated into various palliative approaches in patients with advanced non-small cell lung cancer (NSCLC). Palliative TRT can effectively palliate locoregional symptoms like haemoptysis, cough, shortness of breath, chest pain. Palliative TRT can be given using both hypofractionated and multifractionated regimens. Hypofractionated regimens are convenient to deliver and also cost-effective. Furthermore, hypofractionated palliative TRT may release radiotherapy sources and make radiotherapy more available for other groups of cancer patients.

Lung cancer epidermal growth factor receptor mutations and radiotherapy response: A multicentre clinical study

PurposeTo examine the impact of epidermal growth factor receptor (EGFR) mutations on objective response to palliative lung radiotherapy in patients with metastatic non-small cell lung cancer (NSCLC). Materials and MethodsA multicentre retrospective study was conducted of patients with metastatic NSCLC diagnosed between March 2010 and June 2012 who received palliative radiotherapy to the chest. Patients included for study had baseline imaging and follow-up imaging 1–3 months after radiotherapy. The primary endpoint was 1–3 month local objective imaging response by the Response Evaluation Criteria in Solid Tumours (RECIST). Patients were divided into EGFR mutation positive (EGFR+) and EGFR wild type (WT) cohorts for analysis. ResultsThere were 121 patients for study inclusion: 89 (74%) were EGFR WT and 32 (26%) were EGFR+. The response rate between EGFR WT and EGFR+ cohorts was not significantly different (49 vs. 63%, p = 0.21). On multivariate analysis, initiation of a tyrosine kinase inhibitor (TKI) after radiotherapy was associated with a higher rate of response (OR: 5.07, 95%CI: 1.08–23.69, p = 0.039) but EGFR mutation status was not. For the EGFR+ cohort, patients with disease progression after initial management on a TKI had a worse response rate compared to patients who were TKI-naïve before starting radiotherapy (30 vs. 77%, p = 0.018). Local control was not statistically different between the EGFR cohorts. ConclusionThe EGFR mutation status alone was not an independent predictor of objective radiographic response to palliative thoracic radiotherapy. Acquired resistance to TKI therapy may be associated with disease cross-resistance to palliative radiotherapy.

Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy.

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.

A nomogram to predict the overall survival of patients with symptomatic extensive-stage small cell lung cancer treated with thoracic radiotherapy.

BackgroundSmall cell lung cancer (SCLC) makes up 13% of lung malignancies. Only one-third of SCLC patients received their diagnosis at the limited stage. Treatment for symptomatic extensive-stage (ES) SCLC with persistent intrathoracic disease is still controversial. The present research aimed to analyze the impact of palliative thoracic radiotherapy (TRT) as a treatment for this patient group and build a prognostic nomogram.MethodsIn this retrospective, multi-center study, we analyzed 120 patients with ES-SCLC and a World Health Organization performance status of 1–2 who were diagnosed between March 2014 and September 2019. A nomogram was formulated to predict the patients’ 1- and 2-year overall survival (OS).ResultsThe study cohort had a median age of 62 years, and males accounted for 85% of enrollees. A significant extension was observed in the median OS in the TRT group compared to the no TRT group (P<0.001). When the patients were stratified by TRT dose, no significant differences in OS were noted (P=0.530). However, higher levels of inflammatory markers prior to TRT were associated with a shorter OS (neutrophil-to-lymphocyte ratio, P=0.002; platelet/lymphocyte ratio, P=0.023). The nomogram’s Harrell’s concordance (C)-statistic reached 0.70, and the calibration curve analysis revealed goodness of fit.ConclusionsThe neutrophil-to-lymphocyte ratio is an independent factor predicting survival in ES-SCLC patients treated with palliative TRT. Our nomogram, which incorporates immunological markers, has higher accuracy than existing models for the prediction of individuals’ chances of survival, and it could be a significant tool for clinicians in the development of tailored therapeutic strategies.

P30.06 Outcome Differences Amongst Histopathological Variants of Non Small Cell Lung Cancer Treated With Palliative Radiotherapy

Squamous cell carcinoma and adenocarcinoma are the two major histopathological subtypes of non small cell lung cancer. Amongst these, Squamous Cell subtype is predominant in India. Thoracic palliative radiation therapy offers symptomatic relief to patients with distressing symptoms caused out of loco-regionally advanced disease. But the overall outcome of patients are often dependent upon intrinsic tumor biology and histopathological subtypes, apart from other relevant patient related characteristics. Between August 2018 and January 2020, newly diagnosed 48 patients of histopathologically proven non small cell lung carcinoma, presenting with thoracic distressing symptoms were included in this single armed, single institutional, prospective, observational study, after seeking informed consent from all, out of whom 36 patients had squamous cell carcinoma, while rest 12 had adenocarcinoma. Patients of stage IIIB to IVB, with ECOG performance status 2-3, requiring palliative radiation therapy for relief of local thoracic symptoms were included. All patients were treated with 30 Gy, divided in 10 fractions (3 Gy per fraction), over 2 weeks time (5 days in a week). Treatment response was assessed after 6 weeks of completion of radiation therapy by contrast enhanced CT scan of thorax in accordance with RECIST 1.1 criteria. Patients with partial response and stable disease were considered as treatment responders (having local control) while patients with progressive disease were taken as treatment non-responders. Patients were followed up via phone calls to the patients themselves or to their family members. Survival period was recorded as starting from the time of histopathological diagnosis to the date of death or termination of the study (June 2020). Tabled 1Distribution of patients with two major histopathological subtypes of non small cell lung cancer in accordance with treatment response at 6 weeks post palliative radiation therapyHistopathological subtypesPartial ResponseStable DiseaseProgressive DiseaseSquamous Cell Carcinoma (n=36)12 (33.33%)10 (27.78%)14 (38.89%)Adenocarcinoma (n=12)2 (16.67%)8 (66.67%)2 (16.67%) Open table in a new tab Adenocarcinoma variant responded more to radiation therapy as compared to squamous cell carcinoma in terms of local control (Treatment responders; adenocarcinoma vs squamous cell carcinoma : 83.33% vs 61.11%), though more percentage of patients with squamous cell carcinoma had partial response. Median overall survival (OS) of all 48 patients were 5.85 months. Patients with adenocarcinoma experienced better survival than that of squamous cell carcinoma (Median overall survival; adenocarcinoma vs squamous cell carcinoma : 11.35 vs 4.95 months) after palliative radiation therapy. Adenocarcinoma subtype of non small cell lung cancer tend to have better objective response after palliative thoracic radiotherapy in advanced stage diseases along with better overall survival as compared to squamous cell carcinoma.

Palliative Thoracic Radiotherapy for Non-Small Cell Lung Cancer in Outpatients: Reasons for Unplanned Hospitalization and Its Impact on Survival.

BackgroundThe aims of the study were to examine the rates of and reasons for unplanned hospitalization after start of palliative radiotherapy or chemoradiation (CRT), and to study whether unplanned hospitalization deteriorates patients’ prognosis. In addition, risk factors were identified.MethodsA retrospective review of 136 patients treated with palliative radiotherapy or CRT was performed. Inclusion criteria were prescribed total dose at least 30 Gy and outpatient at the start of treatment. Uni- and multivariate analyses were employed.ResultsFifty-eight patients (43%) were hospitalized within 3 months from start of radiotherapy or CRT. Their median overall survival was 6.7 months as compared to 11.1 months in non-hospitalized patients (P = 0.09). The median length of hospitalization was 8 days (range 1 - 61). In patients with possibly treatment-related hospitalization (n = 32), median survival was 5.0 months, significantly shorter than the 11.1 months observed in the remaining patients (P = 0.006). In multivariate analysis, only one variable was significantly associated with higher risk of unplanned hospitalization: previous hospitalization in the last 4 weeks before commencing radiotherapy or CRT.ConclusionsUnplanned hospitalization occurred frequently in a standard care setting without early involvement of a dedicated palliative team. Patients with preceding hospitalization might represent a group that is particularly vulnerable, thus qualifying for a targeted intervention aiming at continued outpatient care.

Palliative Thoracic Radiotherapy for Non-small Cell Lung Cancer: Is There any Impact of Target Volume Size on Survival?

Recent studies suggested that target volume size impacts survival in patients with non-small cell lung cancer (NSCLC) receiving radical radiotherapy. Little is known about the impact of target volume size in palliative radiotherapy or chemoradiotherapy. Therefore, we analyzed the overall survival stratified for clinical and planning target volume (CTV and PTV) size. A retrospective study of 77 patients who received palliative (chemo)radiotherapy (at least 30 Gy) for non-metastatic NSCLC, largely stage III was performed. Typical radiation doses were 10-13 fractions of 3 Gy and 15 fractions of 2.8 Gy. Median survival was 12 months (2-year rate 18%). Three prognostic factors emerged in the multivariate analysis. Hospitalization in the last 4 weeks before radiotherapy increased the hazard of death by a factor of 2.8 (p=0.002). Presence of a T1 or 2 tumor decreased the hazard of death by a factor of 0.5 (p=0.03). Concomitant chemoradiotherapy decreased the hazard of death by a factor of 0.4 (p=0.003). Target volume size was not significantly associated with survival, suggesting that large size should not preclude palliative (chemo)radiotherapy as long as normal tissue dose constraints can be met.

Practice Recommendations for Lung Cancer Radiotherapy During the COVID-19 Pandemic: An ESTRO-ASTRO Consensus Statement

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk–benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided.ConclusionThis joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.

Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk–benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. ConclusionThis joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.

EP1.01-55 Neoantigen Deletion Leads to Hyperprogressive Disease (HPD) in Non-Small Cell Lung Cancer (NSCLC) Treated with PD-1/PD-L1 Inhibitors

Hyperprogressive disease (HPD) is a distinct pattern of progression described in patients with cancer treated with PD-1/PD-L1 inhibitors. The incidence of HPD is reported to be 13.8% in advanced NSCLC. Recently multiple characteristics have been recognized to predict the risk of HPD, however the mechanism underlying have not been systemically studied. We report a Chinese patient who developed hyperprogressive disease after 4 cycles of PD-1 blockade treatment. Clinical and demographic data was collected from electronic records. Whole exome sequencing (WES) of the primary tumor was performed to identify tumor mutation burden (TMB) and tumor neoantigen burden (TNB) following the restricted pipeline. Liquid biopsy targeting ctDNA and T cell receptor (TCR) was constructed to monitor the efficacy of immunotherapy. A 70-year-old male with smoking history underwent chest CT scan in February 2018 and was found to have a right upper lobe mass with intrapulmonary metastasis in different lobes and multiple lymph nodes. Resection of right lower lung by video-assisted thoracic surgery (VATS) revealed poorly differentiated, squamous cell carcinoma. In July 2018, he progressed after two cycle of chemotherapy and radiation therapy targeting newly bone metastasis of lumbar spine, then he was screened to start Nivolumab at dose of 240mg daily/2 weeks. After four cycle of Nivolumab, he obtained PD and was assigned to palliative thoracic radiation therapy. The PD-L1 expression level of our patient was 1%≤TC<5%, next generation sequencing (NGS) didn’t show alteration in genes related to HPD, such as MDM2/MDM4 or EGFR. Blood sample retrieved before and after immunotherapy revealed the increase in bTMB (from 7.70 Muts/Mb to 18.00 Muts/Mb), however TNB truly expressed as neoantigens were rather lower compared to TMB, indicating the low immunogenicity of tumor. We also found a sharp fluctuate in the detection of driver genes mutations in ctDNA (TP53,CDKN2A,ERBB3,FBXW7), and the majority of high-frequency TCR dropped significantly during immunotharapy. It is reported that NSCLC with a high tumor mutation burden (TMB) may benefit from PD-1/PD-L1 inhibitors treatment, and TMB is considered as the surrogate of tumor neoantigen burden (TNB). However the deletion of neoantigen may occur at different level, including copy number variation at the DNA level, down-regulation of transcription level and inherited variation at the epigenetic level, resulting in the low immunogenicity of primary tumor. Deletion of neoantigen may provide a mechanism of immune evasion which leads to the resistance to PD-1/PD-L1 inhibitors. In this case, treatment of checkpoint inhibitors may activate certain signaling pathway of driver genes to support the hyperprogression disease (HPD). This case report focusing on neoantigen provides a new approach to predict the presence of hyperprogressive disease (HPD) before immunotherapy, and explains the potential mechanism of HPD.