Development Of Radiation Pneumonitis Research Articles

DNA Repair Genetics and the Risk of Radiation Pneumonitis in Patients With Lung Cancer: A Systematic Review and Meta-analysis

AimsERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer. Materials and methodsSNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active. DNA repair SNPs reported by at least two independent studies were pooled for meta-analysis. The study endpoint was radiation pneumonitis (RP) after radiotherapy. Recessive, dominant, homozygous, heterozygous, and allelic genotype models were used where appropriate. ResultsA total of 16 studies (3080 patients) were identified from the systematic review and 12 studies (2090 patients) on 11 SNPs were included in the meta-analysis. The SNPs were ATM rs189037, ATM rs373759, NEIL1 rs4462560, NEIL1 rs7402844, APE1 rs1130409, XRCC3 rs861539, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, ERCC2 rs13181, and XRCC1 rs25487. ERCC1 rs11615 (236 patients) and ERCC2 rs238406 (254 patients) were not significantly associated with RP. Using the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001). ConclusionGenetic variation in the DNA repair pathway genes may play a significant role in the risk of developing radiation pneumonitis in patients with lung cancer. Further studies are needed on genotypic features of DNA repair pathway genes and their association with treatment sensitivity, as such knowledge may guide personalized radiation dose prescription.

Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger

PurposeTo evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). Materials and MethodsTwenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. ResultsThe largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child–Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. ConclusionsAblative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.

Radiothérapie stéréotaxique (RTST) pulmonaire des tumeurs de moins de 3 cm (stade I) et 5 cm (stade II) non opérées : 10 ans d’expérience de l’Institut du Cancer de Montpellier (ICM)

PurposeSearch for predictive factors on survival and local control for less than 3 centimeters (cm) (stage I) and 5cm (stage II) inoperable lung tumors treated by Stereotactic Body Radiation Therapy (SBRT) in a retrospective monocentric study from Montpellier Cancer Institute (ICM) Patients and methodEvery patients treated at ICM for a stage I or II inoperable lung tumors from 2009 to 2019 were analyzed. ResultsOne hundred and seventy nine lesions were treated in 176 patients, with a major part (82,7%) in operated due to chronic obstructive pulmonary disease. Median overall survival for all patients was 71,7 months with a 35 months follow-up and the 2 years loco-regional free survival was 94,0 months. Better associated outcomes were stage I (median overall survival 71,7 versus 29,0 months P=0,004 ; HR=2,37 P=0,005), BED≥150Gy (median time-to-progression not reached versus 76,7 months P=0,025), small size of Planning Target Volume (PTV) (HR=0,42 P=0,032 when PTV<15,6 cc). 7,3% of all patients developed radiation pneumonitis. ConclusionSBRT is associated with an excellent overall survival and a high rate of local control for less than 3cm (stage I) and 5cm (stage II) lung tumors but a low rate of toxicities. For these patients with many comorbidities, BED over 150Gy seems to be associated with a better loco-regional free survival, while cause of death is often other than lung cancer.

Radiotherapy in Lung Cancer: Ally or Foe of Immunotherapy?

Radiotherapy is the most common local treatment for lung cancer. The spectrum of its use ranges from the treatment of early-stage tumors in patients who are not candidates for surgery to the treatment of advanced, unresectable tumors and, very frequently, of metastatic lesions. With great interest, radiotherapy has also been currently cited as a source of neoantigens, stimulating the immune system and enhancing the effect of immunomodulatory drugs. However, the side effects of irradiation on the lung parenchyma and on the immune system can turn it into a hidden foe, impairing patients’ quality of life and survival. Pneumonitis and immunosuppression are two of the side effects of radiotherapy that best exemplify this hidden damage. Studies have shown decreased survival in patients who develop radiation pneumonitis or have a large volume of immune tissue irradiated. Irradiating less lung tissue will reduce damage to lung function and loss of immune cells. However, this alone is not sufficient for dose protection in lymphoid tissue, given the circulation of lymphoid cells in the great vessels and heart and their production in thoracic vertebral bone marrow. Identifying the optimal total dose and the most appropriate daily dose to reduce damage and boost the immune system is the target of our investigations. Although we still do not have an optimal algorithm for dose, fraction, and cost-effectiveness for radiation doses delivered to healthy tissues, we know which path to take.

Implementation and Safety of a Single Fraction Peripheral Lung SBRT during the Global COVID-19 Pandemic, a Single Institution's Experience

Purpose/Objective(s)In response to the COVID-19 pandemic, a single fraction peripheral lung SBRT program was established to minimize potential COVID-19 exposures. This analysis aims to review clinical and treatment characteristics and associated toxicities in appropriately selected patients for this newly implemented technique.Materials/MethodsFrom May 2020 until Feb 2022, patients with peripheral lung tumors who met eligibility for 3400cGy in a single-fraction SBRT were treated at a tertiary academic cancer center. Patient, treatment, and toxicity parameters were retrospectively collected. Radiation dosimetric parameters were tabulated. Toxicities were quantified using CTCAE v5.0. Fisher's exact test was used to assess the differences in toxicities with clinical and dosimetric parameters. P-value < 0.05 was considered significant.Results23 patients were analyzed with a median age of 72 years (IRQ: 67-80) and 61% were females. 96% were smokers and 43% had COPD. All patients were ECOG ≤ 2. Majority of patients (96%) had early-stage primary lung cancer while 4% had pulmonary oligometastatic cancer. 39% of patients were treated on SABR-BRIDGE protocol while another 35% were medically inoperable and 26% refused surgery. A total of 23 peripheral lesions were treated with median greatest dimension of 1.7 cm (IQR: 1.4-2), ITV 4.9 cm3 (IQR: 3.6-8.4) and PTV 18.1 cm3 (IQR: 12.8-26). 87% had PTV within 1 cm form chest wall. After median follow-up of 6 months (IQR: 2-12), 52% of patients experienced grade ≤ 2 toxicities and no patients experienced ≥ grade 3. Radiation pneumonitis was the most common toxicity (35%; 5/8 with asymptomatic radiographic) followed by fatigue (30%) and chest wall pain (30%; 3/7 with grade 2). Two patients (9%) had rib fractures. Chest wall pain was significantly higher in patients with tumor diameter >1.5 cm (p = 0.02). No other significant difference was observed between clinical or dosimetric parameters and development of radiation pneumonitis or chest wall pain (p > 0.05). On the other hand, patients with ribs fractures were observed to have larger tumors (mean 3.2 vs. 1.7 cm), ITVs (mean 30 vs. 11 cm3), PTVs (mean 61 vs. 16 cm3), chest wall V30Gy (mean 4.8 vs. 0.4 cm3), and ribs V30Gy (mean 1.1 vs. 0.1 cm3). Only 1 patient had local failure after 12 months while another patient on SABR-BRIDGE underwent surgical resection after 6 months in which there were 20% viable tumor cells.ConclusionSingle fraction peripheral lung SBRT is a practical and safe option with no grade ≥ 3 toxicity. Our observed toxicities are within previously reported ranges. We observed that patients with rib fractures had larger tumors and higher V30Gy to chest wall and ribs. Careful patient selection and dosimetric efforts to limit high fall-off dose to chest wall and ribs may limit these toxicities.

Association between DNA Repair Gene Pathway Polymorphisms and Risk of Radiation Pneumonitis: A Systematic Review and Meta-Analysis

<h3>Purpose/Objective(s)</h3> Radiation pneumonitis is a dose-limiting toxicity of radiotherapy. Genetic variation in this pathway affects post-radiotherapy DNA repair and subsequently the level of toxicity. Previous studies published within this area in lung cancer treatment have been inconsistent. Our meta-analysis therefore aimed at examining the effect of SNPs on radiation pneumonitis of lung cancer patients receiving radiotherapy. <h3>Materials/Methods</h3> We performed a systematic review of relevant studies published on or before 12 October 2021 on PubMed, Scopus, Embase, and Web of Science databases. Studies with genotyping data of lung cancer patients receiving radiotherapy were included. Conference abstracts, reviews, non-English articles, studies in which radiotherapy was used as a neoadjuvant therapy were excluded. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS) by two independent reviewers. We calculated the pooled odds ratios and the 95% confidence intervals to evaluate the association between each DNA repair gene pathway polymorphism and all-grade radiation pneumonitis. The allelic, dominant, recessive, homozygous and heterozygous genotype models were used to assess the association. <h3>Results</h3> 706 studies were initially obtained after database searching and de-duplication. 15 studies (2964 patients) were included in the systematic review. The median follow-up time ranged from 3 months to 39.5 months. Under the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing radiation pneumonitis compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04, I-square = 0%, total number of patients: 341). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing radiation pneumonitis compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001, I-square = 0%, total number of patients: 432). Other SNPs were found to have no significant associations with all-grade radiation pneumonitis. <h3>Conclusion</h3> This systematic review and meta-analysis showed that two SNPs in the DNA repair gene pathway are significantly associated with the risks of developing radiation pneumonitis in lung cancer patients. Further cohort studies assessing a combination of DNA repair gene polymorphisms with a greater sample size are needed.

Pulmonary Function Testing (PFT) after Photon and Proton Radiotherapy for Stage II-III Breast Cancer

<h3>Purpose/Objective(s)</h3> The Breast Cancer Lung Late Effects (BELLE) study prospectively enrolled patients with breast cancer who received adjuvant photon (XRT) or proton (PT) radiotherapy (RT) to evaluate potential early markers of induced lung injury, including pulmonary function tests (PFTs). <h3>Materials/Methods</h3> Patients ≥18 years with AJCC 8^th edition anatomic stage II-III or greater breast cancer were enrolled into the BELLE study between May 27, 2016 and May 26, 2020. All patients underwent clinical evaluation, computed tomography imaging, PFTs, and QoL questionnaires at baseline, 6 months, and 12 months relative to RT start. Fisher's exact tests and Kruskal-Wallis rank sum tests were used to compare the XRT and PT groups. <h3>Results</h3> A total of 37 patients were included in the final analysis (XRT, n=21; PT, n=16). Median age at diagnosis was 51 years (range, 31-76); 26 patients identified as white (70.3%), 8 as Black (21.6%), and 3 other (7.1%). Most patients did not have pre-existing respiratory disease (83.8%) or prior smoking history (62.2%), while 35.1% were former smokers and 1 was a current smoker (2.7%). The median BMI was 29.4 (range, 18.9-44.2). Most patients received chemotherapy (75.7%) and regional nodal irradiation (RNI; 78.4%). Median lung V20 was 25.3% (range, 5.6-39.7) and median lung V5 was 59.6% (range, 29.7-86.4). XRT patients had more pre-existing respiratory disease and were less likely to receive RNI (p=0.027 and p=0.006, respectively). There was no statistically significant difference between the XRT and PT cohorts for median lung V20 or V5. The median FEV1/FVC ratio at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (80.2 % vs 81.5%, p=0.81; 79.3% vs 81.3%, p=0.95; and 80.6% vs 79.4% p>0.99, respectively). Similarly, the median FVC values at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (3.4 L vs 3.1 L, p=0.76; 3.2 L vs 3.0 L, p=0.38; and 3.5 L vs 3.0 L, p=0.23, respectively). While the median DLCO at baseline was significantly worse for the PT cohort (91% vs 76%, p=0.005), there was no difference between cohorts at 6 and 12 months (79.0% vs 78.0%, p=0.38; 89.0% vs 84.0%, p=0.80, respectively). Four patients developed radiation pneumonitis (RP) within a year of RT including 3 with transient grade 1 (n=1 PT; n=2 XRT) and 1 with grade 3 (XRT). <h3>Conclusion</h3> Despite high variability among patients across all PFT parameters, the median FEV1/FVC ratio and FVC were stable over time and did not cross the threshold for concern of restrictive lung disease in either cohort. Although DLCO decreased at 6 months in the XRT cohort, both cohorts showed improvement at one year without diagnosis of restrictive lung disease. Utilizing PFTs as an early marker of RT-induced lung injury, neither patients treated with XRT nor PT exhibited sustained PFT abnormalities with 1 year of follow-up.

Research Progress on Radiotherapy Combined with Immunotherapy for Associated Pneumonitis During Treatment of Non-Small Cell Lung Cancer.

Radiation pneumonitis is a common and serious complication of radiotherapy for thoracic tumours. Although radiotherapy technology is constantly improving, the incidence of radiation pneumonitis is still not low, and severe cases can be life-threatening. Once radiation pneumonitis develops into radiation fibrosis (RF), it will have irreversible consequences, so it is particularly important to prevent the occurrence and development of radiation pneumonitis. Immune checkpoint inhibitors (ICIs) have rapidly altered the treatment landscape for multiple tumour types, providing unprecedented survival in some patients, especially for the treatment of non-small cell lung cancer (NSCLC). However, in addition to its remarkable curative effect, ICls may cause immune-related adverse events. The incidence of checkpoint inhibitor pneumonitis (CIP) is 3% to 5%, and its mortality rate is 10% to 17%. In addition, the incidence of CIP in NSCLC is higher than in other tumour types, reaching 7%–13%. With the increasing use of immune checkpoint inhibitors (ICls) and thoracic radiotherapy in the treatment of patients with NSCLC, ICIs may induce delayed radiation pneumonitis in patients previously treated with radiation therapy, or radiation activation of the systemic immune system increases the toxicity of adverse reactions, which may lead to increased pulmonary toxicity and the incidence of pneumonitis. In this paper, the data about the occurrence of radiation pneumonitis, immune pneumonitis, and combined treatment and the latest related research results will be reviewed.

Volumetric Estimation of Lung Dose and Its Association with Pneumonitis Following Radiotherapy in Breast Cancer Patients

Introduction: Lung is a major organ at risk during Post Mastectomy RadioTherapy (PMRT), because of the risk of Radiation Pneumonitis (RP). In countries like India 2D RT is widely used due to limited access to advanced technologies. We estimated the lung dose volumetrically in breast cancer patients treated with 2D tangential techniques, the incidence of acute RP and its association with lung dose. Methodology: Retrospective study of patients who underwent PMRT was done. The images with structure sets of cases planned using 2D technique were transferred to TPS and 3 D plans were generated. CLD, MLD, LL were measured from the 2D plan in the CT simulator. LDmean and V20 were measured from from DVH, in the TPS. Correlation between V20 and LDmean was done with CLD, MLD and LL. The incidence of radiation pneumonitis and its association with lung dose also was studied. Result: Total 50 patients were analyzed of which 3 patients had radiation pneumonitis. The mean CLD was 2.28 cm ± 0.54cm, MLD was 2.32 ± 0.6cm and LL was 12.52 ±2cm. V20 for two fields (MT+LT) was 17.04 ± 5.6 Gy and for three field (MT,LT and SCF) was 28.75 ± 8.6 Gy. Positive correlation was found between for V20 &amp; LDmean and CLD, MLD &amp; LL (p&lt;0.05) 6% of patients developed Radiation pneumonitis but did not have association with V20 or MLD. Conclusion: Radiation pneumonitis is major concern after chest wall irradiation and the incidence is expected to be high with conventional technique where the volume is not accurately measured. It is still an option in countries like India with resource constraints by planning cautiously with the indicators of irradiated lung, like CLD and MLD within limits thus minimizing the incidence of radiation induced lung injury.&#x0D;  &#x0D;  

A Semiautomated Chart Review for Assessing the Development of Radiation Pneumonitis Using Natural Language Processing: Diagnostic Accuracy and Feasibility Study.

BackgroundHealth research frequently requires manual chart reviews to identify patients in a study-specific cohort and examine their clinical outcomes. Manual chart review is a labor-intensive process that requires significant time investment for clinical researchers.ObjectiveThis study aims to evaluate the feasibility and accuracy of an assisted chart review program, using an in-house rule-based text-extraction program written in Python, to identify patients who developed radiation pneumonitis (RP) after receiving curative radiotherapy.MethodsA retrospective manual chart review was completed for patients who received curative radiotherapy for stage 2-3 lung cancer from January 1, 2013 to December 31, 2015, at British Columbia Cancer, Kelowna Centre. In the manual chart review, RP diagnosis and grading were recorded using the Common Terminology Criteria for Adverse Events version 5.0. From the charts of 50 sample patients, a total of 1413 clinical documents were obtained for review from the electronic medical record system. The text-extraction program was built using the Natural Language Toolkit Python platform (and regular expressions, also known as RegEx). Python version 3.7.2 was used to run the text-extraction program. The output of the text-extraction program was a list of the full sentences containing the key terms, document IDs, and dates from which these sentences were extracted. The results from the manual review were used as the gold standard in this study, with which the results of the text-extraction program were compared.ResultsFifty percent (25/50) of the sample patients developed grade ≥1 RP; the natural language processing program was able to ascertain 92% (23/25) of these patients (sensitivity 0.92, 95% CI 0.74-0.99; specificity 0.36, 95% CI 0.18-0.57). Furthermore, the text-extraction program was able to correctly identify all 9 patients with grade ≥2 RP, which are patients with clinically significant symptoms (sensitivity 1.0, 95% CI 0.66-1.0; specificity 0.27, 95% CI 0.14-0.43). The program was useful for distinguishing patients with RP from those without RP. The text-extraction program in this study avoided unnecessary manual review of 22% (11/50) of the sample patients, as these patients were identified as grade 0 RP and would not require further manual review in subsequent studies.ConclusionsThis feasibility study showed that the text-extraction program was able to assist with the identification of patients who developed RP after curative radiotherapy. The program streamlines the manual chart review further by identifying the key sentences of interest. This work has the potential to improve future clinical research, as the text-extraction program shows promise in performing chart review in a more time-efficient manner, compared with the traditional labor-intensive manual chart review.

Lung Dose Measured on Postradioembolization 90Y PET/CT and Incidence of Radiation Pneumonitis.

Radiation pneumonitis is a rare but possibly fatal side effect of 90Y radioembolization. It may occur 1-6 mo after therapy, if a significant part of the 90Y microspheres shunts to the lungs. In current clinical practice, a predicted lung dose greater than 30 Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in the literature. In this study, the relationship between the lung dose and the eventual occurrence of radiation pneumonitis after 90Y radioembolization was investigated. Methods: We retrospectively analyzed 317 90Y liver radioembolization procedures performed during an 8-y period (February 2012 to September 2020). We calculated the predicted lung mean dose (LMD) using 99mTc-MAA planar scintigraphy (LMDMAA) acquired during the planning phase and left LMD (LMDY-90) using the 90Y PET/CT acquired after the treatment. For the lung dose computation, we used the left lung as the representative lung volume, to compensate for scatter from the liver moving in the craniocaudal direction because of breathing and mainly affecting the right lung. Results: In total, 272 patients underwent 90Y procedures, of which 63% were performed with glass microspheres and 37% with resin microspheres. The median injected activity was 1,974 MBq (range, 242-9,538 MBq). The median LMDMAA was 3.5 Gy (range, 0.2-89.0 Gy). For 14 procedures, LMDMAA was more than 30 Gy. Median LMDY-90 was 1 Gy (range, 0.0-22.1 Gy). No patients had an LMDY-90 of more than 30 Gy. Of the 3 patients with an LMDY-90 of more than 12 Gy, 2 patients (one with an LMDY-90 of 22.1 Gy and an LMDMAA of 89 Gy; the other with an LMDY-90 of 17.7 Gy and an LMDMAA of 34.1 Gy) developed radiation pneumonitis and consequently died. The third patient, with an LMDY-90 of 18.4 Gy (LMDMAA, 29.1 Gy), died 2 mo after treatment, before the imaging evaluation, because of progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of a lung shunt after 90Y radioembolization is rare (<1%). No radiation pneumonitis developed in patients with a measured LMDY-90 lower than 12 Gy.

Investigating Patient-Reported Outcomes as a Tool for Assessing Risk of Developing Radiation Pneumonitis After Thoracic Radiation in Patients With Non-Small Cell Lung Cancer

Patient reported outcomes (PRO) show promise in predicting which patients are at risk for worst outcomes after chemoradiation (CRT) and may be used to improve symptom management. We investigate if patient-reported symptoms collected during thoracic radiation (TRT) may help identify patients at risk of developing radiation pneumonitis (RP) post-TRT.Between 2016 to 2020, patients with stage III NSCLC treated with definitive-intent TRT at our institution were identified. Patients completed a 10-item symptom-report questionnaire using the PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE v.1.0) weekly during RT and at follow-up. Physicians graded lung-specific symptoms and side-effects using CTCAE v4.0 at the same time-points. RP was defined as radiographic inflammation of the lung within the radiation field attributable to TRT, and excluding other causes. Patient and treatment characteristics were recorded. Descriptive statistics and univariate competing risks analysis were performed to describe and identify variables associated with development of RP.Of 131 patients identified: median age was 66 years, 53% were male, and 45.8% patients had co-morbid lung disease. Patients received a median of 63 Gy (Interquartile range (IQR): 60-63 Gy) with chemotherapy (88%). The median mean-lung-dose (MLD) was 14.5 Gy (IQR: 12-17 Gy) and the median lung V20 was 20% (IQR: 20%-30%). After TRT, 61 patients received immunotherapy. In the entire cohort, twenty-four patients (18%) developed any grade RP, of which n = 21 were grade ≥2. The median time to diagnosis of RP after TRT was 3.0 months. Factors associated with the development of RP included: age (HR 1.06, P = 0.0004) and MLD (P = 0.0005). In terms of PROs associated with development of RP: patient reported severe pain was significantly associated (HR 3.4, P = 0.01), while moderate anxiety (HR 2.3, P = 0.06), and cough (HR 4.53, P = 0.06) were non-significantly associated with RP. Physician assessed grade 2 dyspnea where medical intervention was needed was associated with RP (HR 3.43, P = 0.02).Patient symptom reports during treatment may be associated with the risk development of RP. Larger studies of prospectively collected PROs during TRT are needed to further explore these potential associations with RP.

Correlation Between Lung Density Changes Under Different Dose Gradients and Radiation Pneumonitis—Based on an Analysis of Computed Tomography Scans During Esophageal Cancer Radiotherapy

PurposeTo assess the relationship between different doses of radiation and lung density changes and to determine the ability of this correlation to identify esophageal cancer (EC) patients who develop radiation pneumonitis (RP) and the occurrence time of RP.MethodsA planning computed tomography (CT) scan and a re-planning CT scan were retrospectively collected under institutional review board approval for each of 103 thoracic segment EC patients who underwent radiotherapy (RT). The isodose curve was established on the planning CT with an interval of 5 Gy, which was used as the standard for dividing different gradient doses. Planning CT and re-planning CT scans were matched and the mean lung CT value (HU) between different doses gradients was automatically obtained by the software system. The density change value (ΔHU) was the difference of CT value between each dose gradient before and after treatment. The correlation between ΔHU and the corresponding dose was calculated, as well as the regression coefficients. Additionally the correlation between ΔHU and the occurrence and time of RP (< 4 weeks, 4–12 weeks, > 12 weeks) was calculated.ResultsThe radiation dose and ΔHU was positively correlated, but the correlation coefficient and regression coefficient were lower, 0.261 (P <0.001) and 0.127 (P <0.001), respectively. With the increase of radiation dose gradient, ΔHU in RP≥2 group was higher than that in RP<2 group, and there was significant difference between two groups in ΔHU20-25, ΔHU25-30, ΔHU30-35, ΔHU35-40, ΔHU40-45, ΔHU45-50 (p<0.05). The occurrence time of RP was negatively correlated with the degree of ΔHU (P<0.05), with a high correlation coefficient (Y = week actual value −0.521, P < 0.001) (Y = week grade value −0.381, P = 0.004) and regression coefficient (Y = week actual value −0.503, P<0.001) (Y = week rating value −0.401, P=0.002).ConclusionsA relationship between radiation dose and lung density changes was observed. For most dose intervals, there was an increase of ΔHU with an increased radiation dose, although low correlation coefficient. ΔHU were obvious after irradiation with dose ≥20 Gy which was closely related to the occurrence of RP. For patients with RP, the more obvious ΔHU, the earlier the occurrence of RP, there was a significant negative correlation between them.

Radiation Recall Pneumonitis After Treatment With Checkpoint Blockade Immunotherapy: A Case Series and Review of Literature.

BackgroundRadiation recall pneumonitis (RRP) is a poorly understood clinical syndrome in which patients develop radiation pneumonitis triggered by a systemic agent, often years after the completion of radiation therapy. Immune checkpoint blockade agents have only recently been posited as a trigger for RRP. Here, we present three cases of immunotherapy-induced RRP.Case PresentationOur first patient was diagnosed with primary lung adenocarcinoma, and 4.5 years after completing radiation therapy developed symptomatic RRP immediately following a second dose of nivolumab-containing immunotherapy regimen. Our second patient was diagnosed with primary bladder cancer metastatic to the mediastinum, which was treated twice with radiation therapy. He developed RRP in the days following his second course of ipilimumab-pembrolizumab which was months after his second course of radiation that he received. Our final patient was diagnosed with metastatic small cell lung cancer and received local consolidative radiation therapy in addition to whole-brain radiation. He developed RRP on the 11th day after concluding his 4th cycle of nivolumab-ipilimumab, approximately 7 months after having had completed chest radiation therapy.ConclusionsImmunotherapy-induced RRP is a rare diagnosis which can present more focally than traditional immunotherapy pneumonitis and which must be clinically differentiated from other local processes such as pneumonia. Further research should explore the mechanisms underlying these radiation recall reactions as many patients receive radiation and immunotherapy during the course of their cancer treatment.

Risk factors for radiation pneumonitis in lung cancer patients with subclinical interstitial lung disease after thoracic radiation therapy

BackgroundPrevious studies have found that patients with subclinical interstitial lung disease (ILD) are highly susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. In the present study we aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy in lung cancer patients with subclinical ILD.MethodsWe retrospectively analyzed data from lung cancer patients with subclinical ILD who were treated with thoracic intensity-modulated radiation therapy with a prescribed dose of ≥ 50 Gy in our institution between January 2016 and December 2017.ResultsEighty-seven consecutive lung cancer patients with subclinical ILD were selected for the study. The median follow-up period was 14.0 months. The cumulative incidence of grades ≥ 2 and ≥ 3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, a mean lung dose ≥ 12 Gy was a significant risk factor for grade ≥ 2 RP (p = 0.049). Chemotherapy with gemcitabine in the past, V5 ≥ 50%, and subclinical ILD involving ≥ 25% of the lung volume were significantly associated with grade ≥ 3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively).ConclusionMean lung dose is a significant risk factor for grade ≥ 2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5 ≥ 50%, and those with subclinical ILD involving ≥ 25% of lung volume have an increased risk of grade ≥ 3 RP in lung cancer patients with subclinical ILD.

Multi-Institutional Retrospective Analysis of the Outcomes of Proton Beam Therapy for Patients With 1 to 3 Pulmonary Oligometastases From Various Primary Cancers

PurposeOur purpose was to evaluate the efficacy of proton beam therapy (PBT) in patients with 1 to 3 pulmonary oligometastases from various primary cancers in Japan. Methods and MaterialsThis multi-institutional retrospective survey included 118 patients with 141 metastatic lung tumors from miscellaneous primary cancers, across 6 Japanese institutions, and involved the analyses of local progression-free rate (LPF), distant progression-free rate, progression-free survival rate, cause-specific survival rate, and overall survival rate (OS). Treatment-induced adverse effects of grade ≥2 were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0). Cox proportional hazards regression models were used in univariable analysis and multivariable analysis (MVA) for the identification of the prognostic factors of LPF and OS. ResultsThe median follow-up duration from the time of PBT was 25.5 months. The major primary disease sites included colorectal cancer (42.4%), lung cancer (11.9%), head and neck cancer (8.5%), and kidney cancer (8.5%). For years 1, 2, and 3, LPFs were 92.2%, 86.3%, and 78.4%; distant progression-free rates were 59.1%, 44.1%, and 34.0%; progression-free survival rates were 49.6%, 31.7%, and 24.2%; cause-specific survival rates were 83.4%, 72.5%, and 64.8%; and OS rates were 79.0%, 67.8%, and 59.6%, respectively. Eight patients developed acute adverse effects (grade ≥2). Ten patients developed radiation pneumonitis (grade 2) as a late adverse effect. None of the patients developed severe late toxicity (grade ≥3). Colorectal cancer as the primary disease was the only prognostic factor associated with LPF that remained independently significant in the MVAs performed using 3 sets of parameters (hazard ratio [HR], 3.31-4.76 in 3 MVA sets). In the MVA, the significant prognostic factors for OS were performance status (HR, 2.78; 95% confidence interval, 1.01-7.67) and total tumor volume (HR, 1.01; 95% confidence interval, 1.00-1.02). ConclusionsPBT provides promising outcomes for pulmonary oligometastasis with acceptable toxicities.

Chemoradiotherapy for limited-stage small-cell lung cancer and interstitial lung abnormalities

BackgroundPatients with lung cancer and interstitial lung disease treated with radiotherapy are at risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILAs) and radiation pneumonitis in patients with limited-stage small-cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is uncertain for patients with SCLC and ILAs treated with chemoradiotherapy. We investigated the impact of ILAs on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILAs treated with chemoradiotherapy.MethodsWe retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016.ResultsIn the univariate analysis, the patients with ILAs showed a higher incidence rate of radiation pneumonitis compared with those without ILAs (64% vs. 10%, P < 0.001). Multivariate analysis confirmed that ILAs were significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILAs showed poorer overall survival than those without ILAs (median, 18.9 vs. 67.9 months, P = 0.0338). Multivariate analysis showed that ILAs were a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILAs treated with chemoradiotherapy were 36% and 26%, respectively, and 8% and 0%, respectively, for those treated with chemotherapy alone.ConclusionsILAs were found to be a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. Patients with LS-SCLC and ILAs who were treated with chemoradiotherapy had both the possibility of long-term survival and risk of radiation pneumonitis.

Radiation-induced lung damage in patients treated with stereotactic body radiotherapy after EGFR-TKIs: is there any difference from stereotactic body radiotherapy alone?

To quantitatively evaluate lung damage after treatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and stereotactic body radiotherapy (SBRT) in patients with nonsmall cell lung cancer (NSCLC), and compare that of SBRT only treatment. Eligible patients from an IRB-approved prospective clinical trial had one month of EGFRTKIs treatment followed by SBRT (TKI + SBRT) and with 3-month follow-up high resolution CT. NSCLC patients treated with SBRT alone during the same time period without EGFR-TKIs or other systemic therapies were identified as controls. The lung damage was assessed clinically by pneumonitis and quantitatively using by CT intensity (Hounsfield unit, HU) changes. The mean HU values were extracted for regions of the lungs receiving the same dose range at 10 Gy intervals to generate dose-response curves (DRC). The relationship of HU changes and radiation dose was modeled using a Probit model. Four out of 20 (25%) TKI + SBRT patients and none of 19 (0%) SBRT alone patients had developed grade 2 and above pneumonitis (P=0.053), respectively. Sixty percent of TKI + SBRT patients and 30% SBRT alone patients had HU changes of the normal lung density >200 HU, respectively. There were significant differences in the DRC and in lung HU changes between the two groups (all P<0.05). The physical dose for a 50% complication risk (TD50) of CT lung damage was 52 Gy (CI: 46-59) in TKI + SBRT group versus 72 Gy (CI: 58-107) in SBRT alone group (P<0.01). Compared to patients treated with SBRT alone, patients treated with EGFR-TKIs followed by SBRT were more incline to develop radiation pneumonitis, and resulted in greater lung CT intensity changes and steeper dose-CT lung damage response relationship at 3 months post treatment. Future study with larger number of patients and longer follow-up period is warranted to validate this finding.

Amiodarone Use and Radiation Pneumonitis in Patients Undergoing Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

Stereotactic body radiation therapy (SBRT) has become a standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. Amiodarone is a well-known cause of pneumonitis and an increasing number of patients treated with SBRT are also on amiodarone. Given this potential risk of pulmonary toxicity, it is of interest to examine whether amiodarone may potentiate the risk of RP. We sought to examine the impact of amiodarone use on RP in patients treated with SBRT. Patients with early-stage NSCLC who were taking amiodarone and underwent SBRT from January 2005 to January 2019 were identified from an IRB-approved institutional database. Amiodarone was required to be taken within 3 months before or after SBRT for inclusion. RP status was confirmed using CTCAE guidelines. Follow-up was defined as the time from the end of SBRT treatment until the most recent follow-up or date of death. Thirty-three patients met the inclusion criteria. Median follow up was 14 months (range, 1 to 55 months). The median dose of radiation was 54 Gy (range, 45 to 60) delivered in 3 to 12 fractions. Three patients (9%) developed radiation pneumonitis; all cases of pneumonitis were grade 2. One patient (3%) had a diagnosis of interstitial lung disease (ILD) and no presence of pneumonitis. In this single-institution series, the use of amiodarone in concert with lung SBRT was not associated with numerically increased rates of RP compared with the established literature. These results will need to be validated in larger cohorts with proper control of established metrics (lung V20, ILD), as well as other patient populations such as those undergoing cardiac radio-ablation, where the risks and mechanisms of injury may be different.

65: Feasibility of An Assisted Chart Review for Assessing The Development of Radiation Pneumonitis

65: Feasibility of An Assisted Chart Review for Assessing The Development of Radiation Pneumonitis