Ipsilateral lung dose as a correlative measure for radiation pneumonitis in patients treated with definitive concurrent radiochemotherapy.

Objective: Mean lung dose (MLD) and percent of total lung (TL) volume that receive a dose greater than 20 Gy (V20) have been the most validated parameters in the prediction of radiation pneumonitis (RP). However, these parameters present mean values of TL parenchyma and predict the right and the left lung as a unique functional organ unit, not take into account the difference in function and dose density between the lungs. Furthermore, there have been very limited data evaluating ipsilateral lung dosimetric constraints in addition to TL parameters to predict RP in non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCT). Methods: Between 2010 and 2017, clinical-radiological findings of NSCLC patients treated with RCT were evaluated in terms of RP, retrospectively. MLD, V20, and V30 values of ipsilateral lung were assessed from dose-volume histogram and registered. The primary endpoint was to assess the relation between ipsilateral lung dose constraints and RP risk. Results: There were 75 patients. There was ≥Grade 2 RP in 33 cases (%44). In univariate analysis, ipsilateral MLD, ipsilateral V20, ipsilateral V30, and TL V30 were found to be significant. Ipsilateral MLD and PTV were found to be the independent risk factors for RP. Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL. Conclusions: In NSCLC patients treated with RCT, MLD, V20, and V30 values of ipsilateral lung parameters might increase the predictability of RP risk in addition to TL parameters. Advances in Knowledge: Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL.

New Pulmonary Infiltrates Observed on Computed Tomography-Based Image Guidance for Radiotherapy Warrant Diagnostic Workup for Coronavirus Disease 2019.

INTRODUCTION: Screening for coronavirus disease 2019 (COVID-19) exposure, coupled with engaged decision making to prioritize cancer treatment in parallel with reducing risk of exposure and infection, is crucial in the management of COVID-19 during cancer treatment. After two reported case studies of imaging findings during daily computed tomography (CT)-based image-guided radiotherapy (RT) scans, a call for submission of anonymized case reports was published with the objective of rapidly determining if there was a correlation between the onset of new pulmonary infiltrates found during RT and COVID-19. We hereby report the results of the aggregate analysis. METHODS: Data of deidentified case reports for patients who developed biochemically confirmed COVID-19 during RT were submitted through an online portal. Information requested included a patient's sex, age, cancer diagnosis and treatment, and COVID-19 diagnosis and outcome. Coplanar CT-based imaging was requested to reveal the presence or absence of ground-glass opacities or infiltrates. RESULTS: A total of seven reports were submitted from Turkey, Spain, Belgium, Egypt, and the United States. Results and imaging from the patients reported by Suppli et al. and McGinnis et al. were included for a total of nine patients for analysis. All patients were confirmed COVID-19 positive using polymerase chain reaction-based methods or nasopharyngeal swabs. Of the nine patients analyzed, abnormalities consistent with ground-glass opacities or infiltrates were observed in eight patients. CONCLUSIONS: This is the largest case series revealing the potential use of CT-based image guidance during RT as a tool for identifying patients who need further workup for COVID-19. Considerations for reviewing image guidance for new pulmonary infiltrates and immediate COVID-19 testing in patients who develop new infiltrates even without COVID-19 symptoms are strongly encouraged.

Can consolidative thoracic radiotherapy improve outcomes in extensive-disease small cell lung cancer after chemotherapy with complete/near-complete responders?

BACKGROUND: In extensive-disease-small cell lung cancer (ED-SCLC), the median survival is 8-10 months and 2-year survival is <5%. Primary tumor progression occurs in 90% of patients approximately within 1 year. The role of consolidative thoracic radiotherapy (C-TRT) for the postchemotherapy residue with the aim of improving local control (LC) and survival is currently of great interest. The objective of this study is to determine the effectiveness of C-TRT on LC, progression-free survival (PFS), and overall survival (OS) in ED-SCLC. MATERIALS AND METHODS: Medical records of patients diagnosed as SCLC between January 2010 and December 2015 were evaluated retrospectively. Patients who received C-TRT were identified. Pre- and post-chemotherapy radiological evaluations, radiotherapy schedules, relapse patterns, toxicity incidence, LC, PFS, and OS were analyzed. RESULTS: Among 552 SCLC patients, 26 ED-SCLC patients who underwent C-TRT were analyzed. Median follow-up was 7.5 months (range, 6.5-8.5 months). Nearly 50% of the patients had >4 metastatic lesions. Restaging was performed mostly by positron emission tomography/computed tomography and cranial magnetic resonance imaging. All patients had complete or near-complete response distantly. C-TRT was 10 × 300 cGy (n = 1), 23 × 200 cGy (n = 2), 25 × 200 cGy (n = 7), 30 × 200 cGy (n = 12), and 33 × 200 cGy (n = 4). There was no toxicity ≥ Grade 3. LC rate was 77%; there was no isolated local relapse. PFS was 3 months. Median survival was 13 months. The 1- and 2-year OS rates were 62% and 8%, respectively. CONCLUSION: In ED-SCLC patients, C-TRT may prevent isolated local recurrence and may improve 1-year survival. This survival improvement might be the reflection of high intrathoracic control achieved in 77% of patients.

Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy--Are we underestimating diabetes?--Turkish oncology group (TOG)/Lung cancer study group.

INTRODUCTION: To evaluate the clinical and dosimetric parameters that increase the risk of radiation pneumonitis (RP) in locally advanced non-small cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy of nationwide multicentric data analysis. METHODS: All data of 268 patients who underwent definitive chemoradiotherapy were retrospectively collected from eight institutes participating in this study. Patient, tumor and treatment-related factors and dosimetric parameters were analyzed for grade ≥2 RP. The toxicity scoring system of The Radiation Therapy Oncology Group used for grading the severity of pneumonitis. A relationship with the risk of RP with potential predictive factors were evaluated by univariate and multivariate analyses. A recursive partition analysis (RPA) was applied to stratify patients according to the risk of developing RP. RESULTS: There were 90 (33.6%) patients who had grade ≥2 RP. The median time to pneumonitis after treatment was 4 months (range:1-6 months). In univariate analysis, diabetes mellitus (DM), use of cisplatin/etoposide, total and daily radiotherapy (RT) fraction dose, the planning target volume (PTV) size, mean lung dose, V5, V10 and RT technique were associated with the development of pneumonitis. In multivariate analysis, only DM (P = 0.008) was found to be independent risk factors for RP. According to RPA, the risk of developing RP was highest in patients with DM. CONCLUSIONS: In our study, besides the known dosimetric factors, DM was found to be the most important risk factor causing RP development in multivariate analysis and RPA. The risk is tripled compared to patients without DM.

Radiation-Associated Chronic Dysphagia Assessment by Flexible Endoscopic Evaluation of Swallowing (FEES) in Head and Neck Cancer Patients: Swallowing-Related Structures and Radiation Dose-Volume Effect.

PURPOSE: We aimed to restore dose-volume parameters of swallowing-related structures (SRSs) by evaluating long-term swallowing dysfunctions after radiotherapy (RT) in head and neck cancer patients (HNCPs). MATERIALS AND METHODS: Head and neck cancer patients whose pharyngeal region was involved in RT portal and treated with definitive RT/chemoradiotherapy (CRT) were included in the analyses. Patients underwent objective swallowing assessment by flexible endoscopic evaluation of swallowing (FEES). Volumes of SRSs that received 55 Gy (V55) (mean dose [Dmean]) were evaluated according to the dose-volume histograms of each patient. For every SRS, optimal dose-volume cut-off values were determined by receiver operating characteristic curve analysis. RESULTS: Fifty-five patients at a median 20 months (range, 12-26 months) after their treatments were evaluated. There was a strong negative correlation between FEES scores and dose-volume parameters of SRS ( r ⩽ -0.5, P < .0001). According to our results, middle pharyngeal constrictor (MPC) and inferior pharyngeal constrictor (IPC) had a Dmean > 57 Gy, base of tongue (BOT) Dmean > 50 Gy, supraglottic larynx (SGL) and glottic larynx (GL) Dmean > 55 Gy, and cervical esophagus (CE) Dmean > 45 Gy. MPC V55 > 70%, IPC V55 > 50%, BOT V55 > 65%, CE V55 > 40%, and SGL and GL V55 > 50% were significant predictors for dysphagia. CONCLUSION: It was found that dysphagia correlates strongly with dose-volume parameters of SRSs. IPC, SGL, and CE were found to be structures significantly associated with dysphagia.

Fasting Blood Glucose Level in Locally Advanced Non-Small Cell Lung Cancer: a New Prognostic Factor?

Hyperglycemia may lead to proliferation, invasion, apoptosis inhibition, migration, and eventually metastasis of cancer cells by several mechanisms. In this study, the effect of hyperglycemia on overall survival (OS), disease-free survival (DFS), and locoregional recurrence (LRR) was investigated in NSCLC. One stage IIIA-IIIB NSCLC patient treated with chemoradiotherapy between 2010 and 2015 was enrolled. Fasting blood glucose (FBG) levels were recorded in pre-treatment, treatment, and post-treatment periods. Median age was 54 years (51-62). Fifty-two patients had squamous cell carcinoma (SCC); 19 had adenocarcinoma. Median follow-up was 19 (11-30), median survival was 19 (13-24), and DFS was 9 (7-11) months. Diabetic patients had shorter survival than non-diabetics 12 (95%CI, 10-14) vs. 25 months (95%CI,18-32), p = 0.005. Number of patients with LRR was also higher in diabetics compared to non-diabetics (8/12 vs. 11/37, p = 0.039). OS was shorter in patients with hyperglycemic-FBG and diabetic-FBG levels in pre-treatment period (log-rank p = 0.03 and 0.023, respectively). Diabetic-FBG level in pre-treatment period was found to be the only independent risk factor for survival. In subgroup analysis, these differences were apparent in SCC (log-rank p = 0.009 for hyperglicemic, log-rank p = 0.017 for diabetic-FBG). LRR was 68% in patients with diabetic-FBG, 36.5% in patients with non-diabetic-FBG in post-treatment period (p = 0.015). Patients with LRR had significantly higher median FBG value in post-treatment period compared to non-relapsing patients, 138 mg/dL (119-228) and 111 mg/dL (99-164), respectively (p = 0.022). The patients with hyperglycemic and diabetic-FBG levels in pre-treatment period had shorter survival compared to normoglycemic ones. The patients with diabetic-FBG level in post-treatment period had higher LRR, and relapsing patients had higher FBG levels in post-treatment period.

Is Hippocampal Avoidance During Whole-Brain Radiotherapy Risky for Patients With Small-Cell Lung Cancer? Hippocampal Metastasis Rate and Associated Risk Factors.

OBJECTIVES: Hippocampal avoidance during whole-brain radiotherapy is performed to prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless, the estimated risk of metastases in hippocampal avoidance area in small-cell lung cancer is unknown. The current study aimed to characterize the metastatic distribution within the brain relative to the hippocampus, estimate the incidence of hippocampal metastasis in patients with small-cell lung cancer, and identify clinical and radiographic variables that may be associated with the risk of hippocampal avoidance area metastasis. MATERIALS AND METHODS: Patients with small-cell lung cancer treated with therapeutic whole-brain radiotherapy between January 2010 and December 2015 were reviewed. T1-weighted, postcontrast axial magnetic resonance images obtained just before therapeutic cranial irradiation were retrieved and reviewed for each patient. The hippocampal avoidance area was defined as hippocampus and 5-mm ring area adjacent to the hippocampus to account for necessary dose falloff between the hippocampus and the whole-brain planning target volume. Metastatic lesions within hippocampal avoidance area were defined as hippocampal metastasis. Hippocampal metastasis rate and characteristics of patients with hippocampal metastasis were analyzed and compared to patients without hippocampal metastasis. RESULTS: Fifty-four patients evaluated with cranial magnetic resonance imaging were enrolled. Hippocampal metastasis rate was 32% (17 patients). A total of 4.4% of all metastases involved the hippocampal avoidance area. The most common location was frontal lobe. Being younger than 65 years of age was found to be an independent risk factor for HM (odds ratio: 4.8, 95% confidence interval: 1-23.2, P = .049). The number of brain metastases was significantly higher in patients with hippocampal metastasis ( P = .027), and hippocampal metastasis rate was also higher in patients having larger hippocampus ( P = .026) and larger brain volumes ( P = .02). CONCLUSION: Hippocampal metastasis might be more common in small-cell lung cancer. Reducing the dose to the hippocampus by hippocampal avoiding whole-brain radiotherapy plan in small-cell lung cancer may be risky for the development of HM compared with other malignant solid tumors.

Frequency of Silent Brain Metastasis Before Prophylactic Cranial Irradiation in Small Cell Lung Cancer.

OBJECTIVES: Prophylactic cranial irradiation (PCI) decreases incidence of brain metastasis and improves survival in patients with limited disease-small cell lung cancer (LD-SCLC) who achieved complete response (CR) after treatment. There is no satisfactory evidence about the necessity of new brain imaging for asymptomatic metastasis immediately prior to PCI. The present study aimed to evaluate the frequency of brain metastasis in SCLC patients without neurological symptoms who are candidates for PCI. MATERIAL AND METHODS: The data files of 243 patients with SCLC referred for cranial irradiation were retrospectively reviewed. The patients with following characteristics were enrolled to the study; 1) LD-SCLC patients with CR after chemoradiotherapy who are candidates for PCI. 2) No neurological signs or symptoms of brain metastasis after chemoradiotherapy. 3) Having brain imaging at initial diagnosis and before PCI. RESULTS: Ninety-nine patients (83 male, 83.3%) were included in this study. Median age was 60 years. Time interval between initial and reevaluation for brain metastasis was median 5.5 months (range; 4.7-7.1). Asymptomatic brain metastasis rate was 20.2% (18/99). CONCLUSION: Even if local disease is under control, asymptomatic brain metastasis is not rare. Therefore, patients who are candidates for PCI after completion of chemoradiotherapy should be reimaged for brain metastasis before PCI.

Definitive chemoradiotherapy in Stage III nonsmall cell lung cancer: Turkey experience.

AIM: Concurrent chemoradiotherapy (CRT) is the standard therapy for patients with unresectable Stage III nonsmall cell lung cancer (NSCLC). The aim of this study was to assess the efficacy and safety of concurrent CRT in unresectable Stage III NSCLC in Turkey. PATIENTS AND METHODS: The study included 82 patients with histologically proven unresectable Stage III NSCLC, Eastern Cooperative Oncology Group performance status 0-1, who received concurrent CRT in two different referral centers. Treatment consisted of two cycles of cisplatin at 50 mg/m 2 on days 1, 8, 29, and 36 and etoposide 50 mg/m 2 between days 1 and 5, 29-33 and concurrent radiotherapy administered once daily, 1.8-2.0 Gy per fraction, at a total dose of 60-66 Gy. RESULTS: The stages of the patients were Stage IIIA in 39 (47.5%) and IIIB in 43 (52.5%) patients. Complete and partial responses were achieved in 15 (18.2%) and 31 (37.8%) of the patients, respectively. Twenty-eight (34.2%) patients had stable disease and 8 (9.8) had progressive disease. Forty-one (50%) patients recurred during follow-up. The primary site of recurrence was as distant metastasis in 19 (23.2%) patients. Median overall survival (OS) was 20 months (95% confidence interval; 12.9-27.09 months), 3 and 4 years survivals were 27.9% and 20.9%, respectively. Median progression-free survival (PFS) was 9 months, 3 and 4 years PFSs were 20.1% and 16.1%. Myelosuppression was the most common toxicity. In 15 (19.2%) patients grade 2-3 lung toxicity and in seven (8.5%) patients' grade 2-3 dysphagia were reported. CONCLUSION: Concurrent CRT with cisplatin and etoposide schedule is a well-tolerated regimen with acceptable toxicity profile and survival rates in patients with unresectable Stage IIIA/IIIB NSCLC. Median survival and OS results were consistent with the literature.