Is a Clinical Target Volume (CTV) Necessary in the Treatment of Lung Cancer in the Modern Era Combining 4-D Imaging and Image-guided Radiotherapy (IGRT)?

ObjectiveWe hypothesized that omission of clinical target volumes (CTV) in lung cancer radiotherapy would not compromise control by determining retrospectively if the addition of a CTV would encompass the site of failure.MethodsStage II-III patients were treated from 2009-2012 with daily cone-beam imaging and a 5 mm planning target volume (PTV) without a CTV. PTVs were expanded 1 cm and termed CTVretro. Recurrences were scored as 1) within the PTV, 2) within CTVretro, or 3) outside the PTV. Locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated.ResultAmong 110 patients, Stage IIIA 57%, IIIB 32%, IIA 4%, and IIB 7%. Eighty-six percent of Stage III patients received chemotherapy. Median dose was 70 Gy (45-74 Gy) and fraction size ranged from 1.5-2.7 Gy. Median follow-up was 12 months, median OS was 22 months (95% CI 19-30 months), and LRC at two years was 69%. Fourteen local and eight regional events were scored with two CTVretro failures equating to a two-year CTV failure-free survival of 98%.ConclusionOmission of a 1 cm CTV expansion appears feasible based on only two events among 110 patients and should be considered in radiation planning

Is a Clinical Target Volume (CTV) Necessary in the Treatment of Lung Cancer in the Modern Era Combining 4-D Imaging and Image-guided Radiotherapy (IGRT)?

Objective: We hypothesized that omission of clinical target volumes (CTV) in lung cancer radiotherapy would not compromise control by determining retrospectively if the addition of a CTV would encompass the site of failure. Methods: Stage II-III patients were treated from 2009-2012 with daily cone-beam imaging and a 5 mm planning target volume (PTV) without a CTV. PTVs were expanded 1 cm and termed CTVretro. Recurrences were scored as 1) within the PTV, 2) within CTVretro, or 3) outside the PTV. Locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated. Result: Among 110 patients, Stage IIIA 57%, IIIB 32%, IIA 4%, and IIB 7%. Eighty-six percent of Stage III patients received chemotherapy. Median dose was 70 Gy (45-74 Gy) and fraction size ranged from 1.5-2.7 Gy. Median follow-up was 12 months, median OS was 22 months (95% CI 19-30 months), and LRC at two years was 69%. Fourteen local and eight regional events were scored with two CTVretro failures equating to a two-year CTV failure-free survival of 98%. Conclusion: Omission of a 1 cm CTV expansion appears feasible based on only two events among 110 patients and should be considered in radiation planning

Is a Clinical Target Volume (CTV) Necessary in the Treatment of Lung Cancer in the Modern Era Combining 4-D Imaging and Image-guided Radiotherapy (IGRT)?

ObjectiveWe hypothesized that omission of clinical target volumes (CTV) in lung cancer radiotherapy would not compromise control by determining retrospectively if the addition of a CTV would encompass the site of failure.MethodsStage II-III patients were treated from 2009-2012 with daily cone-beam imaging and a 5 mm planning target volume (PTV) without a CTV. PTVs were expanded 1 cm and termed CTVretro. Recurrences were scored as 1) within the PTV, 2) within CTVretro, or 3) outside the PTV. Locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated.ResultAmong 110 patients, Stage IIIA 57%, IIIB 32%, IIA 4%, and IIB 7%. Eighty-six percent of Stage III patients received chemotherapy. Median dose was 70 Gy (45-74 Gy) and fraction size ranged from 1.5-2.7 Gy. Median follow-up was 12 months, median OS was 22 months (95% CI 19-30 months), and LRC at two years was 69%. Fourteen local and eight regional events were scored with two CTVretro failures equating to a two-year CTV failure-free survival of 98%.ConclusionOmission of a 1 cm CTV expansion appears feasible based on only two events among 110 patients and should be considered in radiation planning

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis

BackgroundRadiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT).MethodsExclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors.Results361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS.ConclusionsWe identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy

Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/Slug pathway

[[abstract]]The ubiquitously expressed glycoprotein Clusterin (CLU) is implicated in diverse cellular processes, yet its genuine molecular function remains undefined. CLU expression has been associated with various human malignancies, yet the mechanisms by which CLU promotes cancer progression and metastasis are not elucidated. In this study, using human lung adenocarcinoma cell lines as a model, we explored the involvement of CLU in modulating invasiveness of cancer cells. We discovered that CLU levels positively correlated with the degree of invasiveness in human lung adenocarcinoma cell lines. The observation that CLU-rich cells displayed a spindle-shape morphology while those with low CLU levels were cuboidal in shape prompted us to investigate if CLU modulates epithelial-to-mesenchymal transitions (EMT). CLU silencing by siRNA in a highly invasive, CLU-rich lung adenocarcinoma cell line induced a mesenchymal-to-epithelial transition (MET) evidenced by the spindle-to-cuboidal morphological change, increased E-cadherin expression, and decreased fibronectin expression. Compared with the vector-transfected cells, CLU-knocked-down (CLUi) cells showed reduced migration and invasion in vitro, as well as decreased metastatic potential in experimental metastasis. Re-expression of CLU in CLUi cells reversed the MET and restored the mesenchymal and invasive phenotypes. We found that Slug, a zinc-finger-containing transcriptional repressor of E-cadherin, was downregulated in CLUi cells. We also discovered that levels of activated ERK correlated with those of CLU and Slug. Taken together, our data suggest that CLU may regulate EMT and aggressive behaviour of human lung adenocarcinoma cells through modulating ERK signalling and Slug expression. 2009 Elsevier Inc. All rights reserved

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis

Background: Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT). Methods: Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors. Results: 361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66–85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67–100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age Conclusions: We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.</p

Effect of COVID-19 on Gynecologic Oncology Care: A Survey of Practicing Gynecologic Radiation Oncologists in the United States

Purpose: The COVID-19 pandemic has placed demands and limitations on the delivery of health care. We sought to assess the effect of COVID-19 on the delivery of gynecologic oncologic care from the perspective of practicing radiation oncologists in the United States. Methods and Materials: An anonymous online survey was created and distributed to preidentified radiation oncologists in the United States with clinical expertise in the management of gynecologic patients. The survey consisted of demographic questions followed by directed questions to assess specific patterns of care related to the COVID-19 pandemic. Results: A total of 47 of 96 invited radiation oncologists responded to the survey for a response rate of 49%. Fifty-six percent of respondents reported an increase in locally advanced cervical cancer with no similar increase for endometrial, vulvar, or vaginal patients. Most respondents (66%) reported a pause in surgical management, with a duration of 1 to 3 months being most common (61%). There was a reported increased use of shorter brachytherapy regimens during the pandemic. Most providers (61%) reported caring for at least 1 patient with a positive COVID-19 test. A pause or delay in treatment due to COVID-19 positivity was reported by 45% of respondents, with 55% reporting that patients chose to delay their own care because of COVID-19–related concerns. Total treatment times >8 weeks for patients with cervical cancer were observed by 33% of respondents, but occurred in >25% of patients. Conclusions: Data from this prospectively collected anonymous survey of practice patterns among radiation oncologists reveal that the COVID-19 pandemic resulted in delays initiating care, truncated brachytherapy treatment courses, and a reported increase in locally advanced cervical cancer cases at presentation. These data can be used as a means of self-assessment to ensure appropriate decision making for gynecologic patients during the endemic phase of COVID-19

Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation

Purpose: Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT) memory impairment. Methods and materials: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Results: Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05). Within this range, the hippocampal V55Gy was the most significant predictor (P = .004). Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively. Conclusions: The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment

Univariate and multivariate analysis of per patient treated metastasis control (TMC).

<p>Univariate and multivariate analysis of per patient treated metastasis control (TMC).</p