Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

BACKGROUND: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. METHODS: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. FINDINGS: Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. INTERPRETATION: 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. FUNDING: Canadian Institutes of Health Research.

Practical Approach to Radiopaque Jaw Lesions.

Radiopaque lesions of the jaw are myriad in type and occasionally protean in appearance. In turn, the radiologic analysis of these lesions requires a systematic approach and a broad consideration of clinical and imaging characteristics to enable reliable radiologic diagnosis. Initially categorizing lesions by attenuation pattern provides a practical framework for organizing radiopaque jaw lesions that also reflects important tissue characteristics. Specifically, the appearance of radiopaque lesions can be described as (a) densely sclerotic, (b) ground glass, or (c) mixed lytic-sclerotic, with each category representing a distinct although occasionally overlapping differential diagnosis. After characterizing attenuation pattern, the appreciation of other radiologic features, such as margin characteristics or relationship to teeth, as well as clinical features including demographics and symptoms, can aid in further narrowing the differential diagnosis and lend confidence to clinical decision making. The authors review the potential causes of a radiopaque jaw lesion, including pertinent clinical and radiologic features, and outline a simplified approach to its radiologic diagnosis, with a focus on cross-sectional CT. An invited commentary by Buch is available online. ©RSNA, 2021.

Prediction of Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer with High PD-L1 Expression Using Baseline CT Disease Quantification and Smoking Pack Years.

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT "number of involved organs" by metastasis and smoking pack years were independently associated with PD (p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort.

Maxillofacial lymphomas.

Lymphomas affecting the bones of the jaws, although less frequent than carcinomas, can both present radiologically as carcinomas in addition to the more frequent "periapical-radiolucencies-of-inflammatory-origin" (PRIOs). Certainly those lymphomas arising within the maxillary alveolus have a short period of prior awareness before presentation, denoting an aggressive process. Half are provisionally diagnosed as carcinomas and the other half as PRIOs. Failure of the latter to respond to appropriate treatment, compels prompt and appropriate investigation for a malignancy. Further distinction of the malignancy into carcinoma and lymphoma is necessary, because the treatment of carcinomas is radical, achieved mainly by resection plus radiotherapy, whereas treatment of lymphomas relies on chemotherapy and in some cases, radiotherapy. The few reported cases that have been subject to cross-sectional imaging and reporting by radiologists has only appeared relatively recently. These cases reveal roles for cone-beam computer tomography, computed tomography and magnetic resonance (MR). Ultimately the diagnosis is dependant on a biopsy from the most representative area/s and the treatment plan upon the diagnosis and extent of the disease defined by the imaging.

Magnetic Resonance Imaging Volumetry of Primary Nasopharyngeal Cancer in Patients Treated with Induction Gemcitabine and Cisplatin Followed by Concurrent Cisplatin and Volumetric Modulated Arc Therapy.

Introduction The addition of induction chemotherapy (IC) to the standard concurrent chemoradiotherapy (CCRT) is under consideration in locally advanced nasopharyngeal carcinoma (LANPC). To-date, no studies have reported primary gross tumour volume (GTVp) changes using gemcitabine and cisplatin as the IC phase in LANPC. We investigated the timing and magnitude of GTVp response throughout sequential gemcitabine and cisplatin IC and CCRT for LANPC. Toxicity and tumour control probability (TCP) analyses are also presented Methods Ten patients with LANPC underwent sequential IC and CCRT between 2011 and 2015. All patients had magnetic resonance imaging (MRI) at three time points: before IC (MRI0), after IC (MRI1), and three months after CCRT (MRI3). Five of the 10 patients had an additional MRI four to five weeks into CCRT (MRI2). GTVp contours were delineated retrospectively using contrast-enhanced MRIs, and each GTVp underwent secondary review by a neuroradiologist. Acute toxicities were graded retrospectively via chart review based on the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0). Results Mean GTVp reduction between MRI0 - MRI1 was from 68 cc to 47 cc and from 47 cc to 9 cc between MRI1 - MRI3. In patients with MRI2, the mean GTVp reduction between MRI1 - MRI2 was from 57 cc to 32 cc. Tumour control probability estimates increased by 0.11 after IC. Patients tolerated the treatment well with one Grade IV toxicity event. Conclusion The observed GTVp response and improved tumor control probability support further investigation into the use of IC in LANPC.

Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose.

OBJECT: The goal in this study was to evaluate hearing preservation rates and to determine prognostic factors for this outcome following fractionated stereotactic radiotherapy (FSRT) of vestibular schwannoma. METHODS: Thirty-four consecutive patients with serviceable hearing who received FSRT between May 1998 and December 2003 were identified. Clinical and audiometry data were collected prospectively. The prescription dose was 45 Gy in 25 fractions prescribed to the 90% isodose line. The median follow-up duration was 36.5 months (range 12-85 months). The actuarial 2- and 4-year local control rates were 100 and 95.7%, respectively. Permanent trigeminal and facial nerve complications were 0 and 6%, respectively. The actuarial 2- and 3-year serviceable hearing preservation rates were both 63%. The median loss in speech reception threshold was 15 dB (range--10 to 65 dB). The radiotherapy dose to the cochlea was the only significant prognostic factor for hearing deterioration. Radiotherapy dose to the cochlear nucleus, patient age, sex, pre-FSRT hearing grade, tumor volume, and intracanalicular tumor volume failed to show any significance as prognostic factors. RESULTS: Five cases were replanned with four different radiotherapy techniques (namely arcs, dynamic arcs, static conformal fields, and intensity-modulated radiotherapy), with the cochlea defined as an organ at risk. In all cases, replanning resulted in statistically significant reduction in radiation to the cochlea (p = 0.001); however, no single replanning technique was found to be superior. CONCLUSIONS: The radiation dose to the cochlea is strongly predictive for subsequent hearing deterioration. It is essential for the cochlea to be outlined as an organ at risk, and for radiation techniques to be optimized, to improve long-term hearing preservation.

Extranodal lymphoma arising within the maxillary alveolus: a case report.

OBJECTIVE: Extranodal lymphomas affecting the head and neck arise infrequently within the bones of the jaws. This is a report of a symptom-free patient whose general dentist detected a radiolucency as an incidental finding on conventional radiography. STUDY DESIGN: The conventional radiography of lesions in the maxilla displayed "floating teeth" indicative of malignancy. This case was then imaged by cone beam computed tomography (CBCT), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI). The lymphoma grew rapidly in less than a week between the MDCT and the MRI. All the above cross-sectional modalities elicited a provisional diagnosis of a squamous cell carcinoma (SCC). CONCLUSIONS: Evaluation of the extent of the lesion and its encroachment on adjacent structures is limited by conventional radiography. Nevertheless, conventional radiography can display features that are suggestive of malignant disease. Although cross-sectional imaging of lesions within the anatomically-complex-maxilla has generally taken the form of MDCT and MRI, CBCT has a role. In hindsight, the absence of central necrosis should have directed the inclusion of "extranodal lymphoma arising within the maxillary alveolus" in the provisional diagnosis.

Factors predictive of symptomatic radiation injury after linear accelerator-based stereotactic radiosurgery for intracerebral arteriovenous malformations.

PURPOSE: To investigate predictive factors in the development of symptomatic radiation injury after treatment with linear accelerator-based stereotactic radiosurgery for intracerebral arteriovenous malformations and relate the findings to the conclusions drawn by Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC). METHODS AND MATERIALS: Archived plans for 73 patients who were treated at the British Columbia Cancer Agency were studied. Actuarial estimates of freedom from radiation injury were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of incidence of radiation injury. Log-rank test was used to search for dosimetric parameters associated with freedom from radiation injury. RESULTS: Symptomatic radiation injury was exhibited by 14 of 73 patients (19.2%). Actuarial rate of symptomatic radiation injury was 23.0% at 4 years. Most patients (78.5%) had mild to moderate deficits according to Common Terminology Criteria for Adverse Events, version 4.0. On univariate analysis, lesion volume and diameter, dose to isocenter, and a V(x) for doses ≥8 Gy showed statistical significance. Only lesion diameter showed statistical significance (p < 0.05) in a multivariate model. According to the log-rank test, AVM volumes >5 cm(3) and diameters >30 mm were significantly associated with the risk of radiation injury (p < 0.01). The V(12) also showed strong association with the incidence of radiation injury. Actuarial incidence of radiation injury was 16.8% if V(12) was <28 cm(3) and 53.2% if >28 cm(3) (log-rank test, p = 0.001). CONCLUSIONS: This study confirms that the risk of developing symptomatic radiation injury after radiosurgery is related to lesion diameter and volume and irradiated volume. Results suggest a higher tolerance than proposed by QUANTEC. The widely differing findings reported in the literature, however, raise considerable uncertainties.

Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors.

BACKGROUND: Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment. RESULTS: In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways. CONCLUSIONS: We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual.

Loss of heterozygosity for loci on chromosome arms 1p and 10q in oligodendroglial tumors: relationship to outcome and chemosensitivity.

Oligodendroglial tumors frequently have deletions ofchromosomal loci on 1p and 19q. Loss of heterozygosity (LOH) of chromosome 10 may be a negative prognostic factor. We reviewed 23 patients with oligodendroglial tumors, to evaluate the frequency of 1p and 10q LOH and correlate with clinical outcome. Three loci (D1S402, D1S1172, MCT118) on 1p and 2 loci (D10S520 and D10S521) on 10q were analyzed for LOH using PCR techniques. Sixteen oligodendrogliomas (6 low grade and 10 anaplastic) and 7 oligoastrocytomas (1 low grade and 6 anaplastic) were studied. Overall 14/22 (64%) showed 1p LOH and 7/23 (30%) showed 10q LOH. Of 7 patients with some response to chemotherapy, all showed 1p LOH and none had 10q LOH. Of 5 patients with stable or progressive disease, 1 had 1p LOH and 2 showed 10q LOH. The presence of 1p LOH was significantly associated with response to chemotherapy (p = 0.02). Median progression free survival (PFS) was 31 months for 1p intact patients and 118 months for the 1p LOH group (p = 0.014). Median PFS for 10q LOH patients was 31 and 118 months for patients with intact chromosome 10 (p = 0.016).1p LOH is a predictor of response to chemotherapy and a good prognostic factor. 10q LOH is less common in oligodendroglial tumors but predicts for worse outcome. Molecular genotyping of oligodendroglial tumors is recommended as part of the standard diagnostic workup.