Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data ...meta-analysis to determine factors predictive of clinically significant pneumonitis.
After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups.
The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio OR 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location.
Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.
Oligometastases: Emerging Evidence Liu, Wei; Bahig, Houda; Palma, David A
Journal of clinical oncology,
12/2022, Letnik:
40, Številka:
36
Journal Article
Recenzirano
The hypothesis that ablative therapies (such as surgery or radiation) can be used to cure patients with a limited number of metastases was influential in changing practice. Early assertions of ...efficacy were based on observational studies, often without control groups, showing better-than-expected outcomes. However, in the past decade, new evidence from randomized trials has emerged, which in some cases have affirmed old hypotheses, but in other cases have raised new questions. In this review, we discuss the challenges in defining oligometastatic disease, summarize the randomized evidence evaluating metastasis-directed therapy in patients with oligometastatic disease, provide context for the difficulty in generating randomized evidence, and examine ongoing phase III studies.
Local ablative therapies, including surgery or stereotactic radiotherapy (SABR), are becoming an integral component in the treatment of oligometastatic disease in non-small-cell lung cancer. In this ...review, we summarize recent randomized evidence supporting progression-free survival and overall survival benefits of local ablation in these patients, as well as upcoming phase III data which should help us better understand the ideal treatment conditions and provide more insight into the oligometastatic state. Since practical management of oligometastatic disease in non-small-cell lung cancer can be challenging, we discuss a modern framework to identify patient, tumor, and treatment characteristics that can best guide management.
The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this ...paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.
This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0–1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1–3 vs 4–5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.
99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19–54) in the control group versus 26 months (23–37) in the SABR group. Median overall survival was 28 months (95% CI 19–33) in the control group versus 41 months (26–not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30–1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5–34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.
SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.
Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
Summary Background Evidence from retrospective studies suggests that disease progression after first-line chemotherapy for metastatic non-small-cell lung cancer (NSCLC) occurs most often at sites of ...disease known to exist at baseline. However, the potential effect of aggressive local consolidative therapy for patients with oligometastatic NSCLC is unknown. We aimed to assess the effect of local consolidative therapy on progression-free survival. Methods In this multicentre, randomised, controlled, phase 2 study, eligible patients from three hospitals had histological confirmation of stage IV NSCLC, three or fewer metastatic disease lesions after first-line systemic therapy, an Eastern Cooperative Oncology Group performance status score of 2 or less, had received standard first-line systemic therapy, and had no disease progression before randomisation. First-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations or ALK rearrangements, respectively. Patients were randomly assigned (1:1) to either local consolidative therapy (chemoradiotherapy or resection of all lesions) with or without subsequent maintenance treatment or to maintenance treatment alone, which could be observation only. Maintenance treatment was recommended based on a list of approved regimens, and observation was defined as close surveillance without cytotoxic treatment. Randomisation was not masked and was balanced dynamically on five factors: number of metastases, response to initial therapy, CNS metastases, intrathoracic nodal status, and EGFR and ALK status. The primary endpoint was progression-free survival analysed in all patients who were treated and had at least one post-baseline imaging assessment. The study is ongoing but not recruiting participants. This study is registered with ClinicalTrials.gov , number NCT01725165. Findings Between Nov 28, 2012, and Jan 19, 2016, 74 patients were enrolled either during or at the completion of first-line systemic therapy. The study was terminated early after randomisation of 49 patients (25 in the local consolidative therapy group and 24 in the maintenance treatment group) as part of the annual analyses done by the Data Safety Monitoring Committee of all randomised trials at MD Anderson Cancer Center, and before a planned interim analysis of 44 events. At a median follow-up time for all randomised patients of 12·39 months (IQR 5·52–20·30), the median progression-free survival in the local consolidative therapy group was 11·9 months (90% CI 5·7–20·9) versus 3·9 months (2·3–6·6) in the maintenance treatment group (hazard ratio 0·35 90% CI 0·18–0·66, log-rank p=0·0054). Adverse events were similar between groups, with no grade 4 adverse events or deaths due to treatment. Grade 3 adverse events in the maintenance therapy group were fatigue (n=1) and anaemia (n=1) and in the local consolidative therapy group were oesophagitis (n=2), anaemia (n=1), pneumothorax (n=1), and abdominal pain (n=1, unlikely related). Interpretation Local consolidative therapy with or without maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress after initial systemic therapy improved progression-free survival compared with maintenance therapy alone. These findings suggest that aggressive local therapy should be further explored in phase 3 trials as a standard treatment option in this clinical scenario. Funding MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, and Cancer Center Support (Core), National Cancer Institute, National Institutes of Health.
Patients with metastatic solid tumors are usually treated with palliative intent. Systemic therapy and palliative radiation are often used, with the goals of prolonging survival or maintaining ...quality of life, but not of cure. In contrast to this paradigm, the theory of oligometastasis suggests that some patients who have a small number of metastases may be amenable to cure if all lesions can be eradicated. Aggressive treatment of patients with oligometastases, using either surgery or radiotherapy, has become more common in the past decade, yet in most situations, no randomized evidence is available to support such an approach. Stereotactic ablative radiotherapy (SABR) is a novel treatment for oligometastases, delivering large doses of radiotherapy in only a few treatments, with excellent rates of local control, and appears to be an excellent noninvasive alternative to surgical resection of metastases. This article reviews recent biologic and clinical data that support the existence of the oligometastatic state and discusses gaps in this evidence base. The emerging role for SABR in the management of this challenging patient population is discussed with a focus on ongoing clinical trials in an attempt to improve overall survival, delay progression, or induce immunologic anticancer effects through the abscopal effect.
Stereotactic ablative radiation therapy (SABR) is a guideline-specified treatment option for early-stage lung cancer. However, significant posttreatment fibrosis can occur and obfuscate the detection ...of local recurrence. The goal of this study was to assess physician ability to detect timely local recurrence and to compare physician performance with a radiomics tool.
Posttreatment computed tomography (CT) scans (n=182) from 45 patients treated with SABR (15 with local recurrence matched to 30 with no local recurrence) were used to measure physician and radiomic performance in assessing response. Scans were individually scored by 3 thoracic radiation oncologists and 3 thoracic radiologists, all of whom were blinded to clinical outcomes. Radiomic features were extracted from the same images. Performances of the physician assessors and the radiomics signature were compared.
When taking into account all CT scans during the whole follow-up period, median sensitivity for physician assessment of local recurrence was 83% (range, 67%-100%), and specificity was 75% (range, 67%-87%), with only moderate interobserver agreement (κ = 0.54) and a median time to detection of recurrence of 15.5 months. When determining the early prediction of recurrence within <6 months after SABR, physicians assessed the majority of images as benign injury/no recurrence, with a mean error of 35%, false positive rate (FPR) of 1%, and false negative rate (FNR) of 99%. At the same time point, a radiomic signature consisting of 5 image-appearance features demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.85, classification error of 24%, FPR of 24%, and FNR of 23%.
These results suggest that radiomics can detect early changes associated with local recurrence that are not typically considered by physicians. This decision support system could potentially allow for early salvage therapy of patients with local recurrence after SABR.
In those undergoing treatment for head and neck cancer (HNC), sarcopenia is a strong prognostic factor for outcomes and mortality. This review identified working definitions and methods used to ...objectively assess sarcopenia in HNC.
The scoping review was performed in accordance with Arksey and O'Malley's five-stage methodology and the Joanna Briggs Institute guidelines.
Eligible studies were identified using MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases.
Inclusion criteria represented studies of adult HNC patients in which sarcopenia was listed as an outcome, full-text articles written in English, and empirical research studies with a quantitative design.
Eligible studies were assessed using a proprietary data extraction form. General information, article details and characteristics, and details related to the concept of the scoping review were extracted in an iterative process.
Seventy-six studies published internationally from 2016 to 2021 on sarcopenia in HNC were included. The majority were retrospective (n = 56; 74%) and the prevalence of sarcopenia ranged from 3.8% to 78.7%. Approximately two-thirds of studies used computed tomography (CT) to assess sarcopenia. Skeletal muscle index (SMI) at the third lumbar vertebra (L3) (n = 53; 70%) was the most prevalent metric used to identify sarcopenia, followed by SMI at the third cervical vertebra (C3) (n = 4; 5%).
Currently, the most effective strategy to assess sarcopenia in HNC depends on several factors, including access to resources, patient and treatment characteristics, and the prognostic significance of outcomes used to represent sarcopenia. Skeletal muscle mass (SMM) measured at C3 may represent a practical, precise, and cost-effective biomarker for the detection of sarcopenia. However, combining SMM measurements at C3 with other sarcopenic parameters-including muscle strength and physical performance-may provide a more accurate risk profile for sarcopenia assessment and allow for a greater understanding of this condition in HNC.
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