Rate Of Radiation Pneumonitis Research Articles

Hypofractionated Radiotherapy Dose Scheme and Application of New Techniques Are Associated to a Lower Incidence of Radiation Pneumonitis in Breast Cancer Patients.

Purpose: Radiation pneumonitis (RP) is one of the most severe toxicities experienced by patients with breast cancer after radiotherapy (RT). RT fractionation schemes and techniques for breast cancer have undergone numerous changes over the past decades. This study aimed to investigate the incidence of RP as a function of such changes in patients with breast cancer undergoing RT and to identify dosimetric markers that predict the risk of this adverse event.Methods and Materials: We identified 1,847 women with breast cancer who received adjuvant RT at our institution between 2015 and 2017. The RT technique was individually tailored based on each patient's clinicopathological features. Deep inspiration breath hold technique or prone positioning were used for patients who underwent left whole-breast irradiation for cardiac sparing, while those requiring regional lymph node irradiation underwent volumetric-modulated arc therapy (VMAT).Results: Of 1,847 patients who received RT, 21.2% received the conventional dose scheme, while 78.8% received the hypofractionated dose scheme (mostly 40 Gy in 15 fractions). The median follow-up period was 14.5 months, and the overall RP rate was 2.1%. The irradiated organ at risk was corrected concerning biologically equivalent dose. The ipsilateral lung V30 in equivalent dose in 2 Gy (EQD2) was the most significant dosimetric factor associated with RP development. Administering RT using VMAT, and hypofractionated dose scheme significantly reduced ipsilateral lung V30.Conclusions: Application of new RT techniques and hypofractionated scheme significantly reduce the ipsilateral lung dose. Our data demonstrated that ipsilateral lung V30 in EQD2 is the most relevant dosimetric predictor of RP in patients with breast cancer.

EP1.18-06 Results of Cytoreductive Wedge Resection of the Primary Site in Multidisciplinary Treatment of Stage III Non-Small Cell Lung Cancer

In patients with stage III non-small cell lung cancer (NSCLC), radical lung resection for curative intent sometimes can not be performed because of the highly local invasiveness of the tumor and/or the patient’ poor general condition. In such cases, combination of radiation therapy, chemotherapy, and sometimes additional immunotherapy is considered. We have performed surgical excisional biopsy by wedge resection for primary site of the lung tumor not only with the diagnostic purose, but also with the intent of cytoreduction and sometimes narrowing the later irradiation range to reduce the risk of radiation pneumonitis (RP). The aim of this study was to determine the results of this cytoreductive wedge resection (CWR) retrospectively, exploring the risk of RP and progression-free survival (PFS). We analyzed the medical records of 64 patients who were diagnosed clinical stage III NSCLC at our hospital between October 2012 and May 2018. The patients were divided into three groups according to the diagnostic method (42 patients were radical resection group, 10 patients were CWR group, and 12 patients were biopsy group that was including the patients diagnosed by surgical incisional biopsy and the primary tumor remained). The relationships between clinicopathological characteristics and the diagnostic method, and PFS among the three groups were investigated. They were aged between 47 and 88 years (average 70.9), and 41 were men. Thirty-seven patients had adenocarcinoma, 19 had squamous cell carcinoma, and 8 had other. No significant difference was found in age, smoking index, performance status, adverse events in chemoradiotherapy among the 3 groups. In the biopsy group, men and squamous cell carcinoma were significantly more compared with the other 2 groups. PFS was not significantly different between the radical resection group and the CWR group but the biopsy group was significantly associated with shorter PFS (median 552 days, 533 days vs. 360 days, p = 0.01). The incidence of RP was 25% in the CWR group and 57% in the biopsy group (p = 0.20). The CWR group showed no inferiority upon PFS compared with the radical resection group. The CWR group showed more than a half rate of RP compared with the biopsy group however this was not statistically significant. It was suggested that the surgical removal of the primary tumor could reach the PFS that is not inferior to the radical resection, and also might reduce the risk of RP compared with the biopsy group.

Metabolic Risk Factors for the Development of Radiation Pneumonitis in Stage III Non-Small Cell Lung Cancer (NSCLC)

Radiation pneumonitis (RP) is a dose-limiting toxicity associated with radiotherapy in the treatment of non-small cell lung cancer (NSCLC). Several studies have linked diabetes as a risk factor for development of radiation-induced lung injury and statin medications as a protective parameter. We aimed to further investigate these findings and explore other metabolic risk factors for the development of RP. After IRB approval, we retrospectively evaluated 162 patients with stage III NSCLC treated with definitive chemoradiation at our institution between 2001 and 2014. Chemotherapy was delivered as couplet therapy with the majority of patients receiving carboplatin-paclitaxel (141/162, 87.2%). Patient information including age, gender, comorbidities, medications, serum glucose values, toxicities, disease, and treatment parameters were collected from patients’ medical records. Serum glucose values spanning from 90 days prior to 90 days post-radiation therapy (n=2870) were collected. We then categorized values into pre-, during, and post-radiotherapy; defined as within 90 days prior to, during, and within 90 days post-radiotherapy. Patients were then stratified into groups achieving serum glucose values ≥150, ≥175, and ≥200 mg/dL at each of the preceding time points. Chi-Squared analyses were used to analyze the effect categorical variables had on the development of RP in our study population. Parameters achieving significance were selected for analysis against pulmonary toxicity grade. We further used a binary logistic regression model to assess how continuous variables may affect the development of RP. The median prescribed dose was 72 Gy (range= 54-84). The overall rate of RP was 17.9% (n=29). In our dataset, 3/46 (6.5%) diabetic patients developed RP vs. 22/101 (21.8%) patients without diabetes (p=0.022). The rate of radiation-induced lung injury in insulin users was 3/42 (7.1%) vs. 22/105 (21.0%) in non-users (p=0.044). Both diabetes (2.2% vs. 14.9%, p=0.022) and insulin (2.4% vs. 14.3%, p=0.036) were associated with lower incidence of RP requiring medical intervention (grade ³2). Diabetes was further correlated with reduced incidence of grade ³3 RP (0% vs. 9.1%, p=0.037). Serum glucose values at the aforementioned time points were not associated with RP. Neither statins nor other diabetic medications correlated with RP risk. Gross tumor volume (GTV), planning target volume (PTV), radiation technique, radiation dose, dose per fraction, and treatment duration were not significant predictors of our primary endpoints. Finally, patients who developed RP had similar rates of mortality, loco-regional recurrence, and distant metastasis to those without. In contrast to prior data, we identify both diabetes and insulin therapy as protective factors against the development of RP in the treatment of NSCLC. These results should be confirmed by subsequent high-quality prospective studies.

Dosimetric Lung Constraints and Neutrophil-Lymphocyte Ratio as Predictors of Radiation Pneumonitis in Lymphoma Patients treated with Mediastinal IMRT

Lung dosimetry is correlated with radiation pneumonitis (RP) in lymphoma patients treated with mediastinal intensity modulated radiation therapy (IMRT). Furthermore, salvage chemotherapy in the refractory setting and the inflammatory milieu may influence toxicity and outcomes. We hypothesized that implementation of strict dosimetric lung constraints (DLCs) would lower the RP rate compared to historical data. We also examined the relationship between pre-IMRT neutrophil-lymphocyte ratio (NLR) and symptomatic RP. We retrospectively reviewed 261 patients with mediastinal lymphoma treated with IMRT between 2009 and 2018; 190 and 71 patients were treated, respectively before and after implementation of DLCs- mean lung dose (MLD) ≤ 13.5 and total lung irradiated to > 5 Gy (V5) ≤ 55%. We compared symptomatic RP incidence before and after DLC implementation and analyzed the clinical, treatment, and dosimetric factors associated with RP. We compared pre-IMRT NLR in patients who did and did not develop RP. Overall, median age was 33 years, 54.4% were female and 82% had stage I/II lymphoma. Also, 75% of patients (n=195) received IMRT after frontline chemotherapy (median dose 30.6 Gy); 25% of patients (n=66) received IMRT after salvage chemotherapy for refractory disease (median dose 39.8 Gy). The RP incidence was lower in patients treated after DLC implementation (5/71) compared to those treated before (27/190) (7.0% vs 14.2%, p=0.12). In patients treated after DLC implementation, 97% (n=69) had MLD ≤ 13.5 Gy and 91% (n=64) had V5 ≤ 55 %. For patients who received IMRT after frontline chemotherapy, RP incidence was significantly lower after implementation of the DLCs (0/49) compared to those treated before (16/146) (0 vs 11%, p=0.02). While the lung V10, V15, V20, and V25 were significantly lower (p<0.05) for patients treated for refractory lymphoma after DLC implementation (n=22) compared to those treated before (n= 44), the incidence of RP was similar in refractory patients treated before (11/44, 25%) and after (5/22, 22.7%) DLC implementation (p>0.05). In the 66 patients who received prior salvage chemotherapy, mean pre-IMRT NLR was significantly lower in patients who developed RP than those who did not (2.04 vs 5.42, p = 0.02). After institutional implementation of MLD ≤ 13.5 Gy and V5 ≤ 55 %, RP incidence was reduced in patients receiving IMRT after frontline chemotherapy, with no patients experiencing RP. However, RP incidence was similar before and after employment of DLCs in patients treated with salvage chemotherapy prior to RT. Thus, stricter DLCs and inflammatory factors may influence RP risk in the salvage population despite lower lung doses after DLC implementation. NLR should be further evaluated as a potential factor associated with RP in lymphoma patients treated with IMRT for refractory disease.

Safety and outcomes of volumetric modulated arc therapy in the treatment of patients with inoperable lung cancer.

Background: Published data on the effects and toxicities of volumetric modulated arc therapy (VMAT) in the management of inoperable lung cancer are scarce.Materials and methods: The clinical outcomes and pulmonary toxicities of 134 patients with consecutive inoperable lung cancer who underwent VMAT from March 2011 to September 2016 were retrospectively reviewed. The dosimetric and characteristic factors associated with acute radiation pneumonitis (RP) and pulmonary fibrosis were evaluated with univariate and multivariate analysis.Results: The average prescription doses to these 134 patients were 57.07±6.27 Gy (range 52-64 Gy). The overall median follow-up time was 18.6 months (range, 2-45 mo), with a median follow-up time for the surviving patients of 20 months (range, 7-45 mo). The 2-year progression-free survival (PFS) and overall survival (OS) for all patients were 18.2% and 38.4%, with a median PFS and OS of 7.6 months and 18.6 months, respectively. The percent of patients with grade III/higher RP and pulmonary fibrosis were 10.5% and 9.0%, respectively. V13 (p=0.02) and age (p=0.02) were independently associated with acute RP according to multivariate analysis. The constraints for lung dosimetric metrics V10,V13,V20 and V30 were approximately 49%,41%,26% and 17% in VMAT treatment of lung cancer to limit the RP rate < 10%.Conclusion: VMAT can be delivered safely with acceptable acute and late toxicities for lung cancer patients. Lung dosimetric metrics were valuable in predicting acute RP. A lung V13 constraint of 40% was helpful to limit the RP rate < 10% in VMAT treatment of lung cancer patients.

Radiation pneumonitis in lung cancer treated with volumetric modulated arc therapy.

Few studies to date have assessed the incidence of radiation pneumonitis (RP) in lung cancer patients who have been treated with volumetric modulated arc therapy (VMAT). This study is aimed at reporting the RP incidence rate and the risk factors associated with a symptomatic RP in patients with lung cancer treated with VMAT. A total of 77 consecutive lung cancer patients treated with VMAT from 2013 through 2015 were reviewed. RP severity was graded according to the Common Terminology Criteria for Adverse Events (CTCEA) v.4. Univariate and multivariate analyses were performed to identify the significant factors associated with RP. VMAT allowed us to achieve most planning objectives on the target volumes and organs at risk, for PTV V95% =96.8%±3.1%, for lung V5 =41.3%±8.7%, V10 =30.0%±7.1%, V20 =20.9%±5.7%, for heart V5 =43.2%±29.9%, for esophagus V60 =8.1%±12.9%. The maximum dose of spinal cord was 34.4±9.5 Gy. The overall incidence of symptomatic RP (grade ≥2 by CTCAE) was 28.6% in the entire cohort, and the rate of grade ≥3 RP was 11.7%. Based on the multivariate analysis, factors predictive of symptomatic RP included lung volume receiving ≥10 Gy (V10) (P=0.019) and C-reactive protein changing level (P=0.013). Our data showed that the incidence rate of RP was acceptable in lung cancer patients treated with VMAT. Additionally, we found that V10 might be an important factor for predicting the development of RP when VMAT was used; but this observation needs to be validated in future studies.

Comorbidity indexing for prediction of the clinical outcome after stereotactic body radiation therapy in non-small cell lung cancer

PurposeTo determine the prognostic impact of comorbidity and age in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) using the age-adjusted Charlson Comorbidity Index (aCCI).Patients and methodsBetween November 2008 and January 2015, 196 consecutive patients with medically inoperable NSCLC were treated with SBRT at a single institution. The prescribed isocenter dose was either 60.0 Gray (Gy) in six fractions for central lung cancer or 56.25 Gy in three fractions for peripheral lung cancer. Baseline comorbidities were retrospectively retrieved according to available outclinic medical records as well as the hospital information system. The aCCI was scored for each patient and subjected according to outcome and toxicity as well as all of the single items of the aCCI and other clinical parameters using univariate and multivariate analysis.ResultsThirty-one point 6 % (62/196) of patients were deceased, of whom 17.3% (34/196) died due to lung cancer and 14.3% (28/196) due to comorbidities. The median overall survival (OS) was 15.0 months (95% CI [11.9–18.1]), whereas the median cancer-specific survival (CSS) was not reached. An aCCI ≥7 compared with an aCCI ≤6 was significantly associated with an increased risk of death (HR 1.79, 95% CI [1.02–2.80], p = 0.04) and cancer-specific death (HR 9.26, 95% CI [4.83–24.39], p < 0.001), respectively. Neither OS nor CCS were significantly associated with age, sex, side (left vs. right), lobe, localization (central vs. peripheral), packyears, TNM, or any item of the aCCI. Considering the 14.3% (28/196) of deceased patients who died due to comorbidities, aCCI ≥9 was significantly associated with non-cancer-related death (HR 3.12, 95% CI [1.22–8.33], p = 0.02). The observed cumulative rate of radiation pneumonitis (RP) ≥2 was 12.7% (25/196). The aCCI had no statistical association with RP.ConclusionAdvanced age and numerous comorbidities characterizing this patient population were successfully assessed using the aCCI in terms of survival. Therefore, we recommend that age and comorbidity be indexed using the aCCI as a simple scoring system for all patients treated with SBRT for lung cancer.

Propensity Score-Matched Analysis to Evaluate the Impact of Re-irradiation on Long-term Prognosis for Recurrent Esophageal Cancer

There was no consensus on the treatment of recurrent esophageal cancer after radiotherapy. Our study aimed to explore whether re-irradiation improves outcomes in recurrent esophageal cancer after primary definitive radiotherapy. We respectively analyzed 70 patients with recurrent esophageal cancer who were treated at our institution, from June 2000 to June 2014. Propensity score matching was used to create patient groups that were balanced across several covariates (age, gender, smoking, drinking, and primary location). The patients were divided into two groups: a re-irradiation group comprising patients who underwent re-radiotherapy (re-RT) and a palliative group, comprising a control group of patients who underwent palliative therapy without re-RT. Outcomes measure included overall survival (OS) and toxicities. The median follow-up was 87 months (range 2-206). The median doses of primary radiotherapy for re-irradiation group and palliative group were 60 Gy (range 40-73) and 66 Gy (range 50-76), respectively. The median dose was 50 Gy (range 21-70) for re-RT. In our follow-up, all the patients in the palliative group died, while seven patients remained alive in the re-irradiation group. The 1-year, 3-year, and 5-year OS in the re-irradiation group and palliative group were 65.9% vs. 28.6%, 24.6% vs. 2.9%, and 14.1% vs. 0%, respectively (P < 0.001). Their median OS was 16 months (range, 2-85) and 6 months (range, 1-60), respectively. Further subgroup analysis did not demonstrate a survival benefit with chemoRT as compared to re-RT alone for recurrent esophageal cancer (P = 0.75). The univariate analysis showed that re-irradiation was the independent prognosis factor for recurrent esophageal cancer (P < 0.001). Regarding toxicities, there were 3 (8.57%) and 2 (5.71%) cases of tracheoesophageal fistulas, 7 (20%) and 1 (2.85%) cases of pericardial/pleural effusion in the re-irradiation group and palliative group, respectively (P > 0.05). The re-irradiation group had a higher rate of radiation pneumonitis (22.8% vs. 5.71%, P = 0.040), but no pneumonia-related deaths occurred. Re-irradiation could improve the long-term prognosis of recurrent esophageal cancer after primary definitive RT. Although the radiation pneumonitis is more frequent in the re-irradiation group, re-irradiation is well tolerated.

Dose-Volume Parameters Predict Radiation Pneumonitis after Surgery with Induction Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer.

To clarify the relationship between dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) after surgery in cases of non-small cell lung cancer (NSCLC) treated with induction concurrent chemoradiotherapy (CCRT). Patients with NSCLC treated with induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 2.0 Gy fractions once daily for a total of 46 Gy) before surgery were reviewed. We calculated the percentage of lung volume receiving at least 20 Gy (V20) and the mean lung dose (MLD) for the total lung volume and the lung remaining after resection. Factors affecting the incidence of RP at grade 2 or higher (≥ G2 RP) were analyzed. Eighteen of 49 patients (37%) experienced ≥G2 RP. The V20 and MLD for the lung remaining after resection (V20r and MLDr) were significant predictors according to the multivariate analysis (p=0.007 and 0.041, respectively). The incidence of ≥G2 RP was 8% in patients with V20r<10%, and 13% in patients with MLDr<5.6 Gy, respectively. The optimal approach to reduce the rate of postoperative RP in patients with induction CCRT for NSCLC is to keep the V20r below 10% and/or the MLDr below 5.6 Gy in the radiotherapy planning.

Efficacy and safety of weekly nab-paclitaxel plus cisplatin with concurrent intensity-modulated radiotherapy in patients with inoperable, locally advanced esophageal cancer: a pilot trial.

BackgroundNab-paclitaxel is produced by the combination of paclitaxel particles with human serum albumin. Encouraging efficacy has been observed with nab-paclitaxel-based chemotherapy in a variety of solid tumors. The aim of the study reported here was to evaluate the efficacy and safety of weekly nab-paclitaxel plus cisplatin with concurrent intensity-modulated radiotherapy in patients with locally advanced esophageal cancer.MethodsSeventeen patients with esophageal cancer were enrolled between July 2014 and December 2015.The treatment included radical radiotherapy (95% planning target volume 60Gy/30f) and concurrent chemotherapy comprising nab-paclitaxel 60mg/m2/week plus cisplatin 25mg/m2/week, administered on days 1, 8, 15, and 22 of each 28-day cycle. The end point of this study included objective response rate (ORR), local-recurrence free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).ResultsAll the patients enrolled in the trial had squamous cell carcinoma. The median follow-up duration was 20.47 months. The ORR was 88.2%. LRFS, DMFS, PFS and OS at 3 years were 61%, 40%, 17% and 35%, respectively. The trial regimen was well tolerated, with grade 3–4 myelosupression, grade 3 radioactive esophagitis, and grade 3 radiation pneumonitis rates of 17.6%, 17.6%, and 11.8%, respectively.ConclusionWeekly nab-paclitaxel plus cisplatin with concurrent intensity-modulated radiotherapy is an effective and well-tolerated treatment option for inoperable, locally advanced squamous cancer of esophageal.

Is severe emphysema, as defined by quantitative CT measurement, a negative risk factor of radiation fibrosis?

To investigate whether patients with emphysema, as evaluated by quantitative CT image measurement, are at risk of developing radiation pneumonitis (RP) after radiotherapy (RT) for non-small cell lung cancer (NSCLC). Between March 2011 and June 2015, 68 consecutive patients with Stage I NSCLC treated with a RT dose of 75 Gy given in 30 fractions were enrolled. The median age was 79 years and there were 45 males and 23 females. The number of patients with T1 and T2 were 49 and 19, respectively. The severity of emphysema was evaluated by the percentages of the low attenuation area (LAA) of ≤-860 or -950 Hounsfield unit (HU) and average HU in the whole lung. The mean difference percentages of LAA of ≤-860 (p = 0.0004) or -950 HU (p = 0.005) and average HU (p = 0.001) in patients with RP were significantly lower than those in patients without RP. The area under curve (AUC) of average HU was significantly higher than AUC of LAA of ≤-860 (p < 0.0001) or -950 HU (p < 0.0001). The RP rate after RT was significantly lower when the average HU values were ≤-850 HU (p = 0.0003). Patients with emphysema evaluated by average HU (≤-850 HU) in the whole lung were found to be at low risk of RP after RT. Advances in Knowledge: Quantitative measurement of average HU from CT images was predicted of RP after RT.

Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer.

Purpose This randomized trial compared outcomes of passive scattering proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT and thereby reduces toxicity without compromising tumor control. The primary end points were grade ≥ 3 radiation pneumonitis (RP) and local failure (LF). Patients and Methods Eligible patients had stage IIB to IIIB NSCLC (or stage IV NSCLC with a single brain metastasis or recurrent lung or mediastinal disease after surgery) who were candidates for concurrent chemoradiation therapy. Pairs of treatment plans for IMRT and PSPT were created for each patient. Patients were eligible for random assignment only if both plans satisfied the same prespecified dose-volume constraints for at-risk organs at the same tumor dose. Results Compared with IMRT (n = 92), PSPT (n = 57) exposed less lung tissue to doses of 5 to 10 Gy(RBE), which is the absorbed Gy dose multiplied by the relative biologic effectiveness (RBE) factor for protons; exposed more lung tissue to ≥ 20 Gy(RBE), but exposed less heart tissue at all dose levels between 5 and 80 Gy(RBE). The grade ≥ 3 RP rate for all patients was 8.1% (IMRT, 6.5%; PSPT, 10.5%); corresponding LF rates were 10.7% (all), 10.9% (IMRT), and 10.5% (PSPT). The posterior probability of IMRT being better than PSPT was 0.54. Exploratory analysis showed that the RP and LF rates at 12 months for patients enrolled before versus after the trial midpoint were 21.1% (before) versus 18.2% (after) for the IMRT group (P = .047) and 31.0% (before) versus 13.1% (after) for the PSPT group (P = .027). Conclusion PSPT did not improve dose-volume indices for lung but did for heart. No benefit was noted in RP or LF after PSPT. Improvements in both end points were observed over the course of the trial.

Clarithromycin mitigates radiation pneumonitis in patients with lung cancer treated with stereotactic body radiotherapy.

Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3. CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be confirmed in prospective studies.

Toxicité aiguë de la tomothérapie des cancers mammaires

PurposeHelical radiation intensity modulated by tomotherapy improves dose distribution to complex and large volumes. The aim of the study was to assess acute toxicity of this technique during breast cancer irradiation after conserving surgery or mastectomy. Patients and methodsCutaneous toxicities, lung and oesophageal side effects, and breast lymphedema were retrospectively collected according to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy between May 2010 and December 2014. After conservative surgery, the dose administered to breast volume and the tumour bed was respectively 52.2Gy and 63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions. Univariate and multivariate analyses were performed to highlight risk factors for dermatitis and breast oedema. ResultsThe rate of dermatitis grade 2 and 3 were 22.9% and 1.7% respectively. In univariate analysis, factors associated with acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI) (P<0.0001), the use of chest compression mask (net) (P=0.005) and the localization of the irradiation (P <0.0001). In multivariate analysis, BMI greater than 25kg/m2 (odds ratio [OR]: 3.61, 95% confidence interval [CI]: [1.93–6.74], P<0.0001), the use of a chest mask (OR 2.01, 95% CI [1.06–3.79] P=0.0328) and irradiation after conservative treatment increase the risk of acute radiation dermatitis (mastectomy: OR 0.64, 95% CI [0.04–0.43]; mastectomy with immediate reconstruction with prosthesis: OR 0.13 95% CI [0.10–0.38] P=0.0003). The incidence of breast oedema grade 2 or above was 19.5%, in univariate analysis, there was a correlation with BMI (P=0.003) and smoking (P=0.009). In multivariate analysis, smoking and BMI greater than 25kg/m2 increased the risk of breast oedema (OR 2.47, respectively [95% CI 1.22–5.01] P=0.012 and OR 2.37 [95% CI 1.22–4.59] P=0.01). The rate of radiation pneumonitis of grade 2 or above was 1.4%. Among the patients, 19.9% had esophagitis grade 1 or 2. ConclusionThe helical irradiation intensity modulation tomotherapy is a well-tolerated treatment for breast cancer that reduces the high radiation doses to organs at risk.

Definitive Chemoradiation Therapy for Esophageal Cancer in the Elderly: Clinical Outcomes for Patients Exceeding 80 Years Old

The optimal treatment approach for patients ≥80years ("elderly") with esophageal cancer is not well established. We assessed the clinical outcomes in elderly patients treated with definitive chemoradiation therapy (CCRT) at our institution. 56 consecutive patients ≥80years with esophageal cancer treated with conventional CCRT between 2001 and 2016 were propensity score matched 1:2 to generate 2 younger patient cohorts treated with CCRT without surgery: "intermediate" (65-79years, n=112) and "younger" (<65years, n=112). Treatment related toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The rates of overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. The median ages of the 3 cohorts were 81years (elderly, 80-92years), 71years (intermediate, 65-79years), and 58years (younger, 20-64years). The elderly cohort was more likely to have cardiac comorbidities. Although the clinical complete response (cCR) rate deviated significantly among the 3 cohorts, (78%, 72%, and 56%; P=.004), the data failed to identify statistically significant differences among RFS, 2-year, and 5-year OS, or in median survival, which was 15.5months, 23.6months, and 20.2months (P=.468), respectively. The overall severe toxicity rates were 38%, 32%, and 30%, respectively (P=.644), including comparable rate of radiation pneumonitis (P>.05). The elderly cohort, however, did show statistically significant evidence of an increased rate of severe radiation pneumonitis (grade ≥3) which was observed to be 11% versus 4% and 0%, respectively (P=.003). The studied elderly population showed evidence of similar long-term clinical efficacy after definitive CCRT when compared with cohorts of younger patients with similar prognostic status. An increased rate of pulmonary toxicity was identified, without evidence of differences for nonpulmonary severe adverse events. Understanding the prognostic risk factors of pulmonary toxicity after CCRT may effectuate improved long-term outcomes for elderly population.

Risk Factors Associated With Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non-small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size ( P = .041), mean lung dose ( P = .028), V2.5 ( P = .024), V5 ( P = .014), V10 ( P = .004), V20 ( P = .024), V30 ( P = .020), V40 ( P = .040), and V50 ( P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 ( P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

Radiation Pneumonitis in Association with Internal Mammary Node Irradiation in Breast Cancer Patients: An Ancillary Result from the KROG 08-06 Study.

PurposeThe aim of this study is to present the incidence of radiation pneumonitis (RP) reported within 6 months after treatment for breast cancer with or without internal mammary node irradiation (IMNI).MethodsIn the Korean Radiation Oncology Group (KROG) 08-06 phase III randomized trial, patients who were node-positive after surgery were randomly assigned to receive radiotherapy either with or without IMNI. A total of 747 patients were enrolled, and three-dimensional treatment planning with computed tomography simulation was performed for all patients. Of the 747 patients, 722 underwent chest X-rays before and within 6 months after radiotherapy. These 722 patients underwent evaluation, and RP was diagnosed on the basis of chest radiography findings and clinical symptoms. The relationship between the incidence of RP and clinical/dosimetric parameters was analyzed.ResultsRP developed in 35 patients (4.8%), including grade 1 RP in 26 patients (3.6%), grade 2 RP in nine patients (1.2%); there was no incidence of grade 3 or higher RP. Grade 2 RP cases were observed in only the IMNI group. The risk of developing RP was influenced by IMNI treatment; pneumonitis occurred in 6.5% of patients (n=23/356) who underwent IMNI and in 3.3% of patients (n=12/366) who did not (p=0.047). The differences in lung dosimetric parameters (mean lung dose, V10–40) were statistically significant between the two groups.ConclusionIMNI treatment resulted in increased radiation exposure to the lung and a higher rate of RP, but the incidence and severity of RP was minimal and acceptable. This minor impact on morbidity should be balanced with the impact on survival outcome in future analyses.

Tomotherapy improves local control and changes failure patterns in locally advanced malignant pleural mesothelioma

PurposeThe purpose of the study was to determine whether intensity modulated radiation therapy delivered via helical tomotherapy improves local control (LC) after pleurectomy/decortication (P/D) for malignant pleural mesothelioma compared with 3-dimensional conformal radiation therapy (3D-CRT). Methods and materialsForty-five consecutive patients were treated with adjuvant radiation to 45 Gy in 1.8 Gy fractions after P/D between 2006 and 2014; 23 received 3D-CRT, and 22 received tomotherapy. Kaplan-Meier analysis was used to calculate overall survival, time to in-field or local failure (LF), and time to out-of-field failure. The Student t test and Fisher exact test were used to detect between-group differences. ResultsMedian follow-up time was 19.4 months and 12.7 months for the 3D-CRT and tomotherapy groups, respectively. Eighty-two percent of patients had T3/T4 disease, and 64% had positive nodes; 17.4% and 41% of patients in the 3D-CRT and tomotherapy groups had nonepithelioid histology, respectively. Mean planning target volume dose, percentage of planning target volume receiving 100% of the prescription dose, and lung doses were significantly greater with tomotherapy (P < .05), but toxicity rates (including radiation pneumonitis rates) were equivalent. LC was significantly improved with tomotherapy on Kaplan-Meier analysis with outcomes censored at 2 years (P < .05); uncensored, this became a trend (P = .06). Median time to LF was 19 months with tomotherapy and 10.9 months in 3D-CRT (the latter interval being less than the median follow-up in the tomotherapy group). On univariate analysis, treatment modality was the only significant predictor of LC (P < .05). Isolated LF was significantly more frequent with 3D-CRT (P < .05). Conversely, isolated out-of-field failure was significantly more frequent with tomotherapy (P < .05). Overall survival and out-of-field control were not significantly different. ConclusionTomotherapy after P/D for malignant pleural mesothelioma is associated with improved target coverage that translates into improved LC compared with 3D-CRT. This is related to a change in failure patterns, with isolated LF being more common in the 3D-CRT group and isolated out-of-field failures predominating in the tomotherapy group.

TH‐AB‐BRB‐04: Dosimetric and Clinical Benefits of Conformal Radiotherapy Plus Volumetric Modulated Arc Therapy in the Treatment of Non‐Small Cell Lung Cancer

Purpose:The purpose of this manuscript is to investigate the dosimetric and clinical benefits of a technique by combining conformal radiotherapy (CRT) plus volumetric modulated arc therapy (VMAT) in the treatment of non‐small cell lung cancer (NSCLC).Methods:There were 200 NSCLC patients analyzed retrospectively and treated by CRT, CRT plus VMAT, and full course of VMAT, respectively. Dosimetric differences, radiation pneumonitis (RP) rates and their correlation were investigated.Results:The number of patients analyzed in CRT, CRT plus VMAT and full course of VMAT were 42, 28, and 53, respectively. The V93 and V95 (percent volume covered by isodose line) of planning target volume (PTV) were improved from 95.7%±2.2% and 94.5%±2.4% in CRT to 97.9%±4.6%, 98.3%±3.2% and 96.3%±5.8%, 97.1%±4.1% in CRT plus VMAT and full course of VMAT, respectively. CRT plus VMAT improved the PTV coverage compared with CRT in a cost of higher spinal cord maximum dose (p=0.02), larger lung volume receiving 5 Gy (V5, p=0.02) and mean lung dose (MLD) (p=0.04), and decreased the low dose lung volumes compared with VMAT. The RP rates were 26%, 39% and 49% for CRT, CRT plus VMAT and VMAT, respectively. V5 was significantly associated with RP and had a threshold of 60% and 65% for CRT plus VMAT and VMAT, respectively, to limit the RP rate &lt;30%.Conclusion:CRT plus VMAT is a promising with increased target coverage compared with CRT and reduced low dose lung volume and RP compared with full course of VMAT in the treatment of NSCLC. V5 was significantly associated with RP and with a predicted threshold of 60% and 65% for CRT plus VMAT and VMAT, respectively, to limit the RP rate &lt;30%. Clinical trials with large population are needed to further verify the benefits of CRT plus VMAT in the treatment of NSCLC.

Risk of Pneumonitis After Stereotactic Body Radiation Therapy in Patients With Previous Anatomic Lung Resection

BackgroundStereotactic body radiation therapy (SBRT) has emerged as a standard treatment of early-stage, medically inoperable lung cancer. Limited data have evaluated the radiation pneumonitis (RP) risk with SBRT after previous anatomic lung resection (ALR). We assessed the incidence of RP and all pulmonary toxicity (PT) in patients who underwent lung SBRT after ALR and compared them with those of patients without previous ALR. Materials and MethodsWe reviewed the medical records of 84 consecutively treated patients with stage T1-T2b non–small-cell lung cancer (NSCLC) treated with 88 courses of SBRT for 94 lung tumors from January 2007 to December 2014, including 17 patients with previous ALR. The rates of RP and all PT were compared between the patients with and without previous ALR. ResultsAt a median follow-up duration of 18.3 months (range, 1.8-85.6 months), the crude grade 2+ RP rate was 5.9% and 2.8% for patients with and without previous ALR, respectively (P = .51). The corresponding 2-year estimates of freedom from RP were 89% and 97% (P = .51). The crude rate of all grade 2+ PT was 11.8% and 2.8% for those with and without previous ALR (P = .11), with 2-year estimates of freedom from PT of 97% and 84% (P = .11), respectively. The 2 cohorts were well matched by the mean lung dose, percentage of lung volume receiving 20 Gy (P = .86), and prescribed dose (P = .75). The 2-year estimates of local control, cause-specific survival, and overall survival were similar between the 2 cohorts. ConclusionThe observed rates of PT were low among all patients, with a trend toward increased grade 2 and 3 lung toxicity among patients with previous ALR. Previous ALR did not increase the risk of grade 4 and 5 RP, and SBRT appears safe and effective in this population.