Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging. However, immunotherapy responses are uniquely challenging to ...interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation. We hypothesized that monitoring tumor cell death in real time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy.
We compared longitudinal changes in ctDNA levels with changes in radiographic tumor size and with survival outcomes in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor therapy. CtDNA was quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using a multigene next-generation sequencing assay. We defined a ctDNA response as a >50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement.
Strong agreement was observed between ctDNA response and radiographic response (Cohen's kappa, 0.753). Median time to initial response among patients who achieved responses in both categories was 24.5 days by ctDNA versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA responders versus nonresponders (median, 205.5 vs. 69 days;
< 0.001). A ctDNA response was associated with superior progression-free survival hazard ratio (HR), 0.29; 95% CI, 0.09-0.89;
= 0.03, and superior overall survival (HR, 0.17; 95% CI, 0.05-0.62;
= 0.007).
A drop in ctDNA level is an early marker of therapeutic efficacy and predicts prolonged survival in patients treated with immune checkpoint inhibitors for NSCLC.
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Radiation Pneumonitis Bledsoe, Trevor J; Nath, Sameer K; Decker, Roy H
Clinics in chest medicine,
06/2017, Letnik:
38, Številka:
2
Journal Article
Recenzirano
Radiation-induced lung injury is a well-known complication of thoracic radiation for patients with breast, lung, thymic, and esophageal malignancies, and mediastinal lymphomas. Improvements in ...radiation technique, as well as the understanding of the pathophysiology of radiation injury, have led to lower rates of pneumonitis and improved symptom control. Here, the authors provide an overview of the pathophysiology, diagnosis, and management of patients with radiation pneumonitis as a complication of treatment of chest malignancies.
Identification of nodal metastasis and tumor extranodal extension (ENE) is crucial for head and neck cancer management, but currently only can be diagnosed via postoperative pathology. Pretreatment, ...radiographic identification of ENE, in particular, has proven extremely difficult for clinicians, but would be greatly influential in guiding patient management. Here, we show that a deep learning convolutional neural network can be trained to identify nodal metastasis and ENE with excellent performance that surpasses what human clinicians have historically achieved. We trained a 3-dimensional convolutional neural network using a dataset of 2,875 CT-segmented lymph node samples with correlating pathology labels, cross-validated and fine-tuned on 124 samples, and conducted testing on a blinded test set of 131 samples. On the blinded test set, the model predicted ENE and nodal metastasis each with area under the receiver operating characteristic curve (AUC) of 0.91 (95%CI: 0.85-0.97). The model has the potential for use as a clinical decision-making tool to help guide head and neck cancer patient management.
Current therapy for small-cell lung cancer (SCLC) relies on chemoradiation therapy, and the role of primary surgical resection in these patients remains controversial. A minority of SCLC patients ...present without metastatic disease and are candidates for surgery. This study investigates the role of surgical resection in select patients with SCLC, using a national cohort of approximately 2500 resected patients.
A retrospective study of SCLC patients in the National Cancer Data Base (NCDB) was performed where patients were grouped for comparison by stage and treatment regimen. Survival was estimated by Kaplan–Meier methods and multivariate comparisons using Cox regression.
Of 28,621 cases of potentially resectable SCLC, 2476 patients (9%) underwent surgery of the primary site with curative intent. Five-year overall survival for patients after resection was 51%, 25%, and 18% for clinical stages I, II, and IIIA, respectively. Addition of surgery to chemotherapy was associated with decreased likelihood of death (hazard ratio: 0.57, 95% confidence interval: 0.47–0.68), independent of age, stage, and comorbidity score. Lobectomy was associated with a 5-year overall survival of 40% compared with 21% and 22% for sublobar resection and pneumonectomy, respectively. Hazard ratio for death after sublobar resections compared with lobectomy was 1.38 (95% confidence interval: 1.12–1.71).
Patients with stages I, II, and III SCLC, who underwent surgical resection as part of initial treatment with chemotherapy had respectable OS. These data may warrant prospective studies of including surgery in the multimodality treatment of SCLC in specific circumstances.
Bullous disorders associated with anti–programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy are increasingly reported and may pose distinct therapeutic challenges. Their ...frequency and impact on cancer therapy are not well established.
To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti–PD-1/PD-L1 therapy.
We retrospectively reviewed the medical records of patients evaluated by the oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018.
We identified 9 of 853 patients who developed bullous eruptions (∼1%) that were treated with anti–PD-1/PD-L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. In all, 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression.
This was a retrospective study from a single tertiary care center.
Bullous disorders developed in approximately 1% of patients treated with anti–PD-1/PD-L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid-sparing agents.
Abstract Objectives Stereotactic body radiotherapy is an effective treatment for patients with early-stage non–small cell lung cancer who are not healthy enough to undergo surgery; however, the ...relative efficacy versus surgery in healthy patients is unknown. The National Cancer Database contains information on patient health and eligibility for surgery, allowing the long-term survival associated with lobectomy and stereotactic body radiotherapy to be compared in healthy patients with clinical stage I disease. Methods The National Cancer Database was queried for patients who underwent lobectomy or stereotactic body radiotherapy for clinical stage I lung cancer between 2008 and 2012. Healthy patients were selected by excluding patients not offered surgery because of health-related reasons and only including patients documented to be free of comorbidities. Results A total of 13,562 comorbidity-free patients with clinical stage I lung cancer treated with lobectomy were compared with 1781 patients treated with stereotactic body radiotherapy. Time-stratified Cox proportional hazards models found lobectomy to be associated with a significantly better outcome than stereotactic body radiotherapy for both T1N0M0 tumors (hazard ratio, 0.38; 95% confidence interval, 0.33-0.43; P < .001) and T2N0M0 tumors 5 cm or less (hazard ratio, 0.38; confidence interval, 0.31-0.46; P < .001). In a propensity-matched analysis of 1781 pairs, lobectomy remained superior to stereotactic body radiotherapy (5-year survival 59% vs 29%, P < .001). Conclusions Among healthy patients with clinical stage I non–small cell lung cancer in the National Cancer Database, lobectomy is associated with a significantly better outcome than stereotactic body radiotherapy. Further study is warranted to clarify the comparative effectiveness of surgery and stereotactic body radiotherapy across various strata of patient health.
Objectives/Hypothesis
The objective was to characterize incidence, treatment, and survival for hypopharyngeal cancer in the United States between 1988 and 2010, and to analyze associations between ...changes in treatment modality and survival.
Study Design
Retrospective cohort study.
Methods
A total of 3,958 adult patients with hypopharyngeal cancer were identified in the Surveillance, Epidemiology, and End Results database. Incidence, treatment, and survival, controlling for patient demographics and disease severity, were analyzed using two‐tailed t tests, Kaplan‐Meier analysis, and univariate and multivariate Cox regression.
Results
The incidence of hypopharyngeal cancer decreased from 1973 to 2010 with an average annual percent change (APC) of −2.0% every year (P < .05). Treatment with laryngopharyngectomy decreased (−2.5% APC, P < .001), treatment with radiotherapy without surgery increased (+2.0% APC, P < .001), and treatment with neither surgery nor radiotherapy increased (+0.5% APC, P < .001) between 1988 and 2010. There was a significant increase in the 5‐year overall survival between 1988 and 1990 and between 1991 and 1995 (P = .024) with no other significant temporal trends in survival. Multivariate analysis revealed that age (65–74, 75–84, or 85+ relative to 18–54 years old), race (white relative to non‐African races), T stage (T2, T3, or T4 relative to T1), N stage (N2 or N3 relative to N0), and treatment modality (−surgery/−radiation, −surgery/+radiation, and +surgery/−radiation relative to +surgery/+radiation) were all significantly associated with worse survival.
Conclusions
Hypopharyngeal cancer has had a decreasing incidence with little change in patient or tumor characteristics. Treatment has increasingly involved radiation without laryngopharyngectomy. This has not been associated with a decrease in survival. Controlling for patient demographics and disease severity, radiation with laryngopharyngectomy is associated with improved survival.
Level of Evidence
2b Laryngoscope, 124:2064–2069, 2014
Stereotactic body radiotherapy (SBRT) has been increasingly utilized for medically inoperable early stage non–small-cell lung cancer. However, a lower biological equivalent dose (BED) is often used ...for central tumors given toxicity concerns, potentially leading to decreased local control (LC). We compared survival, LC, and toxicity outcomes for SBRT patients with centrally versus peripherally located tumors.
We included patients with primary cT1-2N0M0 non–small-cell lung cancer treated with SBRT at our institution from September 2007 to August 2013 with follow-up through August 2014. Central tumor location was defined as within 2 cm of the proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Kaplan–Meier analysis and multivariable Cox regression modeling were used for overall survival (OS) and LC, and the χ2 test and multivariable logistic regression modeling were used for toxicity.
We included 251 patients (111 central, 140 peripheral) with median follow-up of 31.2 months. Patients with central tumors were more likely to be older (mean 75.8 versus 73.5 years; p = 0.04), have larger tumors (mean 2.5 cm versus 1.9 cm; p < 0.001), and be treated with a lower BED (mean 120.2 Gy versus 143.5 Gy; p < 0.001). Multivariable analysis revealed that tumor location was not associated with worse OS, LC, or toxicity. Patients with central tumors were less likely to have acute grade greater than or equal to three toxicity than those with peripheral tumors (odds ratio: 0.24; p = 0.02).
Central tumor location did not predict for inferior OS, LC, or toxicity following SBRT when a lower mean BED was utilized.
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