A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated ...with a combination of cetuximab and nivolumab.
Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m2 i.v. and nivolumab 240 mg i.v. on day 1 and day 15 of each 28-day cycle. Expression of p16 and programmed cell death-ligand 1 (PD-L1) in archived tumors were determined. Tumor-tissue-modified human papillomavirus (TTMV) DNA was quantified in plasma.
Ninety-five patients were enrolled, and 88 patients were evaluable for OS with a median follow-up of 15.9 months. Median OS in the 45 patients who had prior therapy for R/M HNSCC (cohort A) was 11.4 months, with a 1 year OS 50% 90% confidence interval (CI), 0.43-0.57. Median OS in the 43 patients who had no prior therapy (cohort B) was 20.2 months, with a 1-year OS 66% (90% CI, 0.59-0.71). In the combined cohorts, the p16-negative immunostaining was associated with higher response rate (RR; P = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (P = 0.03) and longer OS (log-rank P = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (P = 0.01) and longer OS compared with higher median (log-rank P = 0.05).
The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.
We hypothesized the combination of cetuximab and nivolumab would improve survival in recurrent and/or metastatic (R/M) HNSCC by providing synergy in cancer control and evaluated toxicities and ...efficacy of the combination. Effects of sequential administration of cetuximab and anti-Programmed Cell Death-1 checkpoint inhibitors (CPI) were also explored. Patients who failed at least one line of palliative treatment for incurable HNSCC were treated with cetuximab 500 mg/m
IV on Day (D)-14 as a lead-in followed by cetuximab 500 mg/m
IV and nivolumab 240 mg/m
IV on D1 and D15 every 28-D cycle. Electronic health record-derived real-world data (RWD) were used to explore sequential treatment effects of CPI and cetuximab. A total of 45 evaluable patients were analyzed, and 31/45 (69%) patients had prior exposure to either CPI or cetuximab. The only grade 4 treatment-related adverse event was cetuximab infusion reaction in one patient. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 19% and 44%, respectively. Although patients with no prior CPI (23/45, 51%) showed a trend for more favorable PFS relative to patients with prior CPI (22/45, 49%), the improvement in the 1-year OS did not reach the statistical threshold. For evaluation of sequential CPI and cetuximab treatment effects, we selected RWD-cetuximab cohort with 173 patients and RWD-CPI cohort with 658 patients from 6862 R/M HNSCC. Our result suggested patients treated with RWD-cetuximab after RWD-CPI had worse OS compared to no prior RWD-CPI (HR 1.81, 95% CI 1.02-3.16). Our data suggest the combination of cetuximab and nivolumab is well tolerated. Optimal sequencing of cetuximab and CPI may have an impact in prognosis and requires further evaluation.
•Occult contralateral nodal disease rate in surgically-managed HPV+ OPSCC is not definitively known.•Multi-institutional population of resectable oropharyngeal cancers.•Occult contralateral nodal ...metastases rate was low (7.4% in the entire cohort; 5% in the p16+ cohort).
Knowledge of the rate of occult contralateral nodal disease for oropharynx cancers (OPSCC) in the era of Human Papillomavirus-dominated disease would inform practitioners as to who may be a candidate for unilateral neck management. The objective of this study was to determine the rate of pathologic contralateral positive nodes in patients in OPSCC patients with pT1 and pT2 disease treated with TORS and bilateral neck dissections (BND).
Retrospective review of medical records was performed at Princess Margaret Cancer Center, Toronto; Icahn School of Medicine at Mount Sinai, New York City; and Montefiore Medical Center, New York City. Patients with pT1-2 N0-3 (AJCC 8th Edition) OPSCC disease treated with TORS and BND were included.
Thirty-two patients met inclusion criteria. Twelve patients (37.5%) had a tonsil primary site, 19 (59.4%) patients had a base of tongue primary site, and 1 (3.1%) patient had a pharyngeal wall primary. Twenty-four (75%) patients were known to be p16+. Twenty-seven patients (84.4%) were radiographically negative in the contralateral neck preoperatively, and two of these patients had pathologic contralateral positive nodes. The occult pathologic contralateral nodal metastasis rate was 7.4% (2/27). The sensitivity, specificity, positive predictive value, and negative predictive value of suspicious contralateral nodes on preoperative imaging for pathologically positive nodes were 33.3%, 86.2%, 20% and 93% respectively. In the p16+ subgroup, the occult nodal positive rate in the contralateral neck was 5%.
pT1-2 OPSCC patients undergoing TORS and elective contralateral neck dissection have a low rate of pathologic contralateral nodal positivity.
BACKGROUND Gangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, ...particularly serine–threonine protein kinase B-RAF alterations. Fusions involving neurotrophin tyrosine receptor kinase ( NTRK ) genes have rarely been reported in ganglioglioma. Similarly, echinoderm microtubule-associated protein-like ( EML ) 4 gene fusion has been described in lung cancer, but none has been reported in ganglioglioma. OBSERVATIONS This report discusses the care of a 72-year-old man presenting with medication-refractory, left-sided focal seizures who was found to have a nongadolinium-enhancing, T2-hyperintense, right frontoparietal lesion. The patient received resection, and histological analysis found a World Health Organization grade I ganglioglioma, with genetic analysis demonstrating an EML4-NTRK3 gene fusion protein. LESSONS To our knowledge, this is the first report of an NTRK3 fusion, EML4-NTRK3 , in an adult ganglioglioma, which is otherwise mostly associated with BRAF alterations and activation of the mitogen-activated protein kinase signaling pathway. Further studies are needed to elucidate the function of the resultant fusion protein and determine whether it may serve as a future therapeutic target.
The transition toward value-based payment models increases focus on the radiologist's direct impact on hospital-provided patient care. Radiology trainees understand inpatient hospital workflows and ...decision-making paradigms and are well positioned to interface directly with hospital physicians regarding clinical decision making related to diagnostic imaging and/or image guided interventions. A radiology resident-led project with internal medicine residents focused on Clinical Decision Support was designed, implemented, and reviewed, with the objectives of educating clinical teams and positively impacting patient care.
During the 2017-2018 academic year, senior radiology residents (PGY-5) led weekly rounds with medicine residents rotating through inpatient floor units. During these rounds, they discussed indications for and types of hospital inpatient imaging studies, exchanged clinical information, directed further imaging workup, and taught the essentials of image interpretation. Participating medical residents’ degree of radiology-awareness and opinions were systematically surveyed at the conclusion of the academic year. Thirty-four out of a total of 161 (21%) Internal Medicine residents responded to the survey. Thirty one percent of these residents could identify an instance where radiology-led rounds altered patient management and 94% acknowledged an increase in medical knowledge. Sixty-one percent believed evidence-based choice for imaging orders was enhanced by attending radiology-led rounds and 64% developed a better understanding of resources available to guide image ordering. Forty-nine percent of residents made suggestions to their Internal Medicine attending physician or more senior trainee or otherwise applied something learned during radiology-led rounds and 42% cancelled or ordered a study based on what they learned or discussed in radiology rounds. Thirty-nine percent of medicine residents stated that these rounds changed their perception of the role of the radiologist and 75% expressed the desire to see increased participation by radiologists in their daily workflow. Radiology resident-led educational medicine rounds promote cross-specialty collaboration, further educate trainees, and directly affect patient management. It is therefore valuable for radiology trainees to directly engage in the teaching of other medical providers, to enhance their own consultative skill set, promote face-to-face interactions with other physicians, and to directly impact patient care.
Background
Head CT scans are considered the imaging modality of choice to screen patients with head trauma for neurocranial injuries; however, widespread CT imaging is not recommended and much ...research has been conducted to establish objective clinical predictors of intracranial injury (ICI) in order to optimize the use of neuroimaging in children with minor head trauma.
Objective
To evaluate whether a strict application of the New Orleans Criteria (NOC), Canadian CT Head Rule (CCHR) and National Emergency X-Radiography Utilization Study II (NEXUS II) in pediatric patients with head trauma presenting to a non-trauma center (level II) could reduce the number of cranial CT scans performed without missing clinically significant ICI.
Materials and methods
We conducted an IRB-approved retrospective analysis of pediatric patients with head trauma who received a cranial CT scan between Jan. 1, 2001, and Sept. 1, 2008, and identified which patients would have required a scan based on the criteria of the above listed decision instruments. We then determined the sensitivities, specificities and negative predictive values of these aids.
Results
In our cohort of 2,101 patients, 92 (4.4%) had positive head CT findings. The sensitivities for the NOC, CCHR and NEXUS II were 96.7% (95%CI 93.1–100), 65.2% (95%CI 55.5–74.9) and 78.3% (95%CI 69.9–86.7), respectively, and their negative predictive values were 98.7%, 97.6% and 97.2%, respectively. In contrast, the specificities for these aids were 11.2% (95%CI 9.8–12.6), 64.2% (95%CI 62.1–66.3) and 34.2% (95%CI 32.1–36.3), respectively. Therefore, in our population it would have been possible to scan at least 10.9% fewer patients.
Conclusions
The number of cranial CT scans conducted in our pediatric cohort with head trauma would have been reduced had any of the three clinical decision aids been applied. Therefore, we recommend that further validation and adoption of pediatric head CT decision aids in non-trauma centers be considered to ultimately increase patient safety while reducing medical expense.
Dural metastases and meningiomas are extraaxial lesions that may be difficult to distinguish using conventional imaging methods. This distinction, however, is clinically important. Perfusion MRI may ...play a role in preoperative assessment. The aim of this study was to evaluate the utility of perfusion parameters in differentiating between these two entities. In particular, we evaluated two new metrics that reflect the first-pass wash-in characteristics of perfusion.
Patients with intracranial extraaxial masses who underwent perfusion MRI were included. Region-of-interest analysis was performed and several perfusion metrics were calculated including relative cerebral blood volume (rCBV), mean transit time and time to peak (TTP) enhancement from initial bolus enhancement (T0), calculated as TTP-T(0). Two new metrics characterizing first pass wash-in enhancement were also measured: relative wash-in time and wash-in slope. Lesions were divided into two groups: meningioma and metastasis. Comparisons between the two groups were made using Wilcoxon rank sum and Fisher exact tests.
Twenty lesions were studied (12 meningioma and 8 metastases). Compared with meningiomas, relative wash-in time was statistically lower in metastases (p < 0.05). No other statistically significant differences were observed. Specifically, there was no difference between the two study groups in rCBV.
First-pass wash-in characteristics of dural lesions may be useful for evaluating and characterizing lesions. In particular, a metric describing the wash-in phase of perfusion-that is, relative wash-in time-was found to be lower in metastases compared with meningiomas. Contrary to a prior report, we found rCBV to be limited in the evaluation of extraaxial lesions.
Background: Intracerebral ring enhancing lesions can be the presentation of a variety of pathologies, including neoplasia, inflammation, and autoimmune demyelination. Use of a precise diagnostic ...algorithm is imperative in correctly treating these lesions and minimizing potential adverse treatment effects.
Case Description: A 55-year-old patient presented to the hospital with complaints of a post-concussive syndrome and a non-focal neurologic exam. Imaging revealed a lesion with an open ring enhancement pattern, minimal surrounding vasogenic edema, and minimal mass effect. Given the minimal mass effect, small size of the lesion, and nonfocal neurological exam, we elected to pursue a comprehensive noninvasive neurologic workup because our differential ranged from inflammatory/infectious to neoplasm. Over the next 8 weeks, the patient's condition worsened, and repeat imaging showed marked enlargement of the lesion with a now closed ring pattern of enhancement with satellite lesions and a magnetic resonance (MR) spectroscopy and perfusion signature suggestive of neoplasm. The patient was taken to surgery for biopsy and debulking of the lesion. Surgical neuropathology examination revealed glioblastoma multiforme.
Conclusion: The unique open ring enhancement pattern of this lesion on initial imaging is highly specific for a demyelinating process, however, high-grade glial neoplasms can also present with complex and irregular ring enhancement including an open ring sign. Therefore, other imaging modalities should be used, and close follow-up is warranted when the open ring sign is encountered.
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