Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT

COVID-RO study: the radiation oncology practice at times of COVID-19 outbreak — international survey

Background: Radiation therapy (RT), an essential treatment of cancer, involves multiple hospital visits. We hypothesized that radiation departments would adjust their work patterns and RT protocols in response to the SARS-CoV-2 pandemic. Materials and methods: An electronic survey was sent during April 2020 to an international sample of radiation oncologists. The survey explored various aspects of departmental preparedness, and changes to their institutional RT protocols. Results: A total of 68 radiation oncologists from 13 countries answered the survey. Healthcare systems were at least moderately affected in 76%. Most institutes appeared well prepared for the outbreak: regarding the availability of personal protective equipment, tests, and telemedicine/videoconference facilities. Screening for SARS-CoV-2 was applied in 59% of responders. Modification of RT protocols were minor in 66%, significant in 19% and no changes made in 15%. The extent to which protocols were modified correlated with overall healthcare disruption (p = 0.028). Normal fractionation was recommended to continue in 83% and 85% of head & neck, and cervical cancers vs. 64% of lung cancers (p = 0.001). In case the pandemic worsens, there was strong agreement to prioritize RT for aggressive cancers (80%), delay RT for slow-growing tumors (78%) and change to evidance-based hypofractionations protocols (79.4%). The option of delayed/omitted adjuvant RT  (not site specific) was selected in 47%.  Conclusion: This international survey concludes that, by making significant organizational adjustments and minor protocol modifications, RT may be safely continued during this pandemic. If the crisis worsens, there was strong agreement to continue the treatment of aggressive tumors and utilize evidence-based hypofractionated protocols

Long-Term Survival of Patients with Metastatic Non-Small-Cell Lung Cancer over Five Decades

Objective. Novel therapeutics and supportive care improved outcomes for metastatic non-small-cell lung cancer (mNSCLC) patients. Major advances over the past five decades include the introduction of combination chemotherapy, small molecules targeting mutant proteins, especially EGFR, and more recently immunotherapy. We aim to document real-world long-term survival over the past five decades. Methods. Survival statistics were extracted from the Survival, Epidemiology, and End Results (SEER) database for mNSCLC patients during 1973–2015. Two- and five-year survival (2yS and 5yS) were analyzed using Kaplan–Meier and proportional hazard models. Results. The study population consisted of 280,655mNSCLC patients diagnosed during 1973–2015. Longer survival was seen in younger, female, married, Asian/Pacific Islander race, adenocarcinoma, lower grade, more recent diagnosis, higher income, and chemotherapy-treated patients. 2yS increased during the study period from 2.6% to 12.9%, and 5yS increased from 0.7% to 3.2%. 2yS of patients <50 years of age rose from 2.1% to 22.8%, and their 5yS rose from 0.7% to 6.2%. 2yS of adenocarcinoma patients improved from 2.7% to 16.2%, and their improved 5yS from 1.1% to 3.9%. Conclusions. Between 1973 and 2015, there was a dramatic improvement in long-term survival, with an approximately five-fold increase in both 2yS and 5yS. Nonetheless, absolute numbers of long-term survivors remained low, with less than 4% living 5 years. This provides a baseline to compare long-term outcomes seen in the current generation of clinical trials

Total dose, fraction dose and respiratory motion management impact adrenal SBRT outcome

Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites. However, the optimal radiation dose for long-term local control of adrenal metastases has yet to be determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control. Materials/Methods: After IRB approval, a retrospective data review of patients treated with SBRT for adrenal metastases at a medical center in Israel between 2015 and 2021 was conducted. A biological effective dose was calculated using an alpha beta ratio of 10. Kaplan Meier and Cox regression were calculated using SPSS software to describe the hazard ratio for local control and survival. Results: 83 cases of adrenal SBRT were identified. The average age was 67 (range 42–92 years old). Non-small cell lung cancer was the primary site in 44 % of patients. A total of 70 % of the patients had oligometastatic disease (less than five lesions), and the rest were polymetastatic, responding to systemic therapy with oligo progression in the adrenal. The average gross tumor volume (GTV) was 42 ml. Respiratory control was applied in 88 % of cases; 49.3 % used 4-D/ITV, and 38.5 % used breath-hold or continuous positive airway pressure (CPAP) with free breathing. On multivariable analysis, Dose above 75 Gy (biological effective Dose) (HR = 0.41, p = 0.031), Dose above 8 Gy per fraction (HR = 0.53p = 0.038), and breath-holds or CPAP (HR = 0.65, p = 0.047) were significant for local control. From multivariable analysis, we computed a predicted nomogram curve using seven clinical parameters to evaluate local control odds. Conclusion: In this single institution series reported to date, we found unilateral adrenal SBRT safe, yet bilateral treatment harbors a risk of adrenal insufficiency. Biological effective Dose > 75 Gy (BED), motion management with breath-hold or CPAP, and Dose per fraction > 8 Gy were the enhanced local controls. We propose a nomogram to help in decision-making regarding total Dose and Dose per fraction when treating adrenal SBRT

Reexpansion of atelectasis caused by use of continuous positive airway pressure (CPAP) before radiation therapy (RT)

Introduction: Although radiation therapy (RT) is an effective treatment for malignant atelectasis, its accurate delivery is challenging because of difficulty differentiating between tumor and atelectatic lung. Furthermore, reexpansion of lung during treatment repositions tumor and normal structures necessitating replanning to ensure treatment accuracy. Facilitating lung reexpansion before initiation of RT may improve RT treatment accuracy, spare normal tissue, and reduce obstructive symptoms. We report a case of reexpansion of right upper lobe (RUL) atelectasis caused by use of continuous positive airway pressure (CPAP) before RT. Case report: A 52-year-old woman presented with dyspnea and cough. Imaging studies showed an RUL mass with atelectasis. Bronchoscopy showed extrinsic compression of the RUL and middle lobe bronchi. Biopsy showed small cell lung cancer. Staging with positron emission tomography-computed tomography (CT) and contrast enhanced CT of brain showed no other disease. Following 4 cycles of platinum-based chemotherapy, CT imaging showed a decrease in tumor volume, but persistent RUL atelectasis. She agreed to participate in an institutional study to evaluate the use of CPAP to reduce respiratory motion and immobilize tumors during RT. During CPAP training, she complained of vertigo, headache, and weakness and refused simulation. The next day she reported less dyspnea and completed training and CT simulation without difficulty. CT simulation with CPAP showed reexpansion of the RUL. Lung volume increased from 2170 to 3767 mL (74 %). Gross tumor volume, clinical volume, and planning volume decreased 46%, 45%, and 38%, respectively. Mean lung dose and mean heart dose decreased 20% and 51%, respectively. CPAP was used daily for 1 hour before and during treatment. Cone beam CT scans showed that the RUL remained inflated throughout treatment. Conclusion: This is the first reported use of CPAP for reexpansion of atelectasis before RT planning and treatment. Reexpansion of atelectasis improved RT planning, decreased dose to uninvolved lung, and removed the need for replanning. Further study of CPAP as an initial intervention to improve RT delivery in patients with malignant atelectasis is warranted

The IASLC Thymic Epithelial Tumors Staging Project: unresolved issues to be addressed for the next 9th edition of the TNM classification of malignant tumors

: Thymic epithelial tumors are presently staged using a consistent tumor, node and metastasis (TNM) classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC). The stage classification is incorporated in the 8th edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC) - Thymic Domain is in charge for the next (9th) edition expected in 2024. The present paper represents the mid-term report of the SPFC Thymic Domain: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the 9th edition of the TNM classification based on the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics (CRAB). These issues are grouped into issues of general importance, and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-Thymic Domain for the discussion of the 9th edition is provided

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors

International audienceIntroduction: In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification. Methods: A central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world. Results: A total of 11,347 patients were collected. Submitting organizations were the following: Japanese Association for Research in the Thymus, European Society of Thoracic Surgeons, Chinese Alliance for Research in Thymoma, Korean Association for Research in the Thymus, International Thymic Malignancy Interest Group, and Réseau tumeurs THYMiques et Cancer. Additional contributions came from centers in the United States, United Kingdom, Turkey, Australia, Spain, and Italy. A total of 9147 cases were eligible for analysis. Eligible cases for analysis came from Asia and Australia (5628 cases, 61.5%), Europe (3113 cases, 34.0%), and North America (406 cases, 4.4%). Conclusions: This report provides an overview of the database that has informed the proposals for the updated T, N, and M components and the stage groups for the ninth TNM of malignant tumors

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors

International audienceIntroduction: A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the ninth edition stage classification system. This article outlines the proposed definitions for the T categories for the ninth edition TNM stage classification of thymic malignancies. Methods: A worldwide collective database of 11,347 patients with thymic epithelial tumors was assembled. Analysis was performed on 9147 patients with available survival data. Overall survival, freedom-from-recurrence, and cumulative incidence of recurrence were used as outcome measures. Analysis was performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors. Results: Proposals for the T categories include the following: T1 category is divided into T1a (≤5 cm) and T1b (>5 cm), irrespective of mediastinal pleura invasion; T2 includes direct invasion of the pericardium, lung, or phrenic nerve; T3 denotes direct invasion of the brachiocephalic vein, superior vena cava, chest wall, or extrapericardial pulmonary arteries and veins; and T4 category remains the same as in the eighth edition classification, involving direct invasion of the aorta and arch vessels, intrapericardial pulmonary arteries and veins, myocardium, trachea, or esophagus. Conclusions: The proposed T categories for the ninth edition of the TNM classification provide good discrimination in outcome for the T component of the TNM-based stage system of thymic epithelial tumors