Kristen J. Otto

Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology

ThyroSeq v2 claims high positive (PPV) and negative (NPV) predictive values in a wide range of pretest risks of malignancy in indeterminate thyroid nodules (ITNs) (categories B-III and B-IV of the Bethesda system). We evaluated ThyroSeq v2 performance in a cohort of patients with ITNs seen at our Academic Cancer Center from September 2014 to April 2016, in light of the new diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Our study included 182 patients (76% female) with 190 ITNs consecutively tested with ThyroSeq v2. Patient treatment followed our institutional thyroid nodule clinical pathway. Histologies of nodules with follicular variant papillary thyroid carcinoma or NIFTP diagnoses were reviewed, with reviewers blinded to molecular results. ThyroSeq v2 performance was calculated in nodules with histological confirmation. We identified a mutation in 24% (n = 45) of the nodules. Mutations in RAS were the most prevalent (n = 21), but the positive predictive value of this mutation was much lower (31%) than that in prior reports. In 102 resected ITNs, ThyroSeq v2 performance was as follows: sensitivity 70% (46-88), specificity 77% (66-85), PPV 42% (25-61) and NPV 91% (82-97). The performance in B-IV nodules was significantly better than that in B-III nodules (area under the curve 0.84 vs 0.57, respectively; P = 0.03), where it was uninformative. Further studies evaluating ThyroSeq v2 performance are needed, particularly in B-III.

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

OBJECTIVE Several molecular marker tests are available to refine the diagnosis of thyroid nodules. Knowing the true prevalence of malignancy (PoM) within each cytological category is considered necessary to select the most appropriate test and to interpret results accurately. We describe our institutional PoM among cytological categories and report our experience with molecular markers. DESIGN Single-center retrospective study. METHODS We calculated the institutional PoM for each category of the Bethesda system (Bethesda) on all thyroid nodules with cytological evaluation from October 2008 to May 2014. We estimated the predictive values for Afirma, miRInform, and ThyroSeq v2, based on published sensitivity and specificity. Finally, we assessed our own experience with miRInform. RESULTS The PoMs for Bethesda III and IV categories were 21 and 28%, respectively. ThyroSeq v2 achieves the highest theoretical negative and positive predictive values (NPV and PPV) in Bethesda III (98 and 75%) and Bethesda IV categories (96 and 83%). At our institution, miRInform detected a mutation in 16% of 109 indeterminate nodules tested, all in Bethesda IV specimens. Histology was available in 56 (51%) nodules. The observed sensitivity and specificity in Bethesda IV specimens were 63 and 86%, yielding an NPV and a PPV of 75 and 77%, respectively. CONCLUSIONS For our current Bethesda III and IV PoM, the actual performance of miRInform was worse than expected. Theoretically ThyroSeq v2 should have the best performance, but it could be affected in the same way as miRInform, given the similarities between the tests. Assessing the institutional performance of each test is necessary along with PoM individualization.

Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiotherapy for locally advanced head and neck cancer

BACKGROUND Cisplatin dosed every 3 weeks (CIS) or weekly cetuximab (CTX) concurrent with radiotherapy are standards of care for locally advanced head and neck squamous cell carcinoma (LAHNC). Retrospective comparisons of CIS and CTX have offered mixed conclusions. We compared outcomes between CIS and CTX in this patient population. METHODS Between January 2006 and December 2011, we identified 279 patients who underwent definitive radiotherapy and concurrent systemic therapy for LAHNC. The median age difference between the CIS and CTX groups was relatively small (58 vs. 62 years, respectively) and CIS patients had a slightly higher rate of N2 disease than CTX patients (74% vs. 61%, respectively). RESULTS Median follow-up was 27 months. Systemic therapy consisted of CIS in 241 (86.4%) and CTX in 38 (13.6%). Actuarial locoregional control of the CIS and CTX groups at 2 years were 91% and 90% (p=0.74), respectively. Actuarial 2 year distant metastasis rates between the groups were 8% and 12%, respectively (p=0.55), and actuarial 2 year overall survival between the groups were 87% and 89%, respectively (p=0.47). CONCLUSIONS We found no difference in locoregional control, distant metastasis rate, or overall survival between patients treated with concurrent CIS or CTX.

Induction docetaxel, Cisplatin, and 5-Fluorouracil precludes definitive chemoradiotherapy in a substantial proportion of patients with head and neck cancer in a low socioeconomic status population.

Objectives:In this retrospective study we evaluate the tolerability and outcomes after induction chemotherapy for patients with predominately low socioeconomic status (SES) with locally advanced head and neck cancer (LAHNC). Methods:One hundred eighteen patients with LAHNC of the hypopharynx, larynx, oral cavity, or oropharynx began curative intent therapy with induction cisplatin (75 or 100 mg/m2), docetaxel (75 mg/m2), and 5-fluorouracil (750 mg/m2×5 d or 1000 mg/m2×4 d; continuous infusion) every 3 weeks (DPF) for a planned 2 to 3 cycles. All patients were to receive curative radiotherapy with concurrent systemic therapy. Associations were tested using &khgr;2 test, and survival estimates were calculated using the Kaplan-Meier method. Results:Most patients (75.4%) were of low SES. Induction DPF was delivered for a median of 2 cycles (range, 1 to 3) and 14% of the patients (n=17) died during induction DPF. After DPF, 38.2% of patients were unable to complete or receive planned definitive therapy. Overall 15.3% of patients died during therapy, and mortality was associated with a Karnofsky performance status <80 (P=0.04). At 2 years the locoregional control was 52.7%, whereas the distant metastases free rate was 72.6%, and the overall survival rate was 34.1%. Low SES patients were less likely to achieve locoregional control (P=0.05) or survive (P=0.08). Conclusions:In this population of LAHNC patients of low SES with a high tumor burden and poor performance status, use of induction DPF was associated with 15.3% mortality during therapy and precluded 38.2% of patients from initiating or completing planned definitive therapy.

Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer

Determining the optimal follow‐up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus‐positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management.

Adjuvant radiotherapy versus concurrent chemoradiotherapy for the management of high-risk salivary gland carcinomas

Given the aggressive behavior of advanced salivary malignancies, the purpose of the current study was to explore the utility of adjuvant chemoradiotherapy (CRT) in this population.

Increased acute mortality with chemoradiotherapy for locally advanced head and neck cancer in patients ≥70 years

PURPOSE Concurrent chemoradiotherapy (CRT) is the standard of care for many sites of locally advanced head and neck squamous cell carcinomas (LAHNC). However, on meta-analysis, the addition of chemotherapy did not improve survival for patients >70years. We hypothesized that elderly patients treated with CRT would have increased toxicity without similar improvements in survival. METHODS A single-institution, IRB-approved retrospective study took place from 2005 to 2012 including 369 patients treated with CRT for LAHNC. Multivariate models for death at 3months and death over time were developed using logistic regression and Cox modeling, respectively. RESULTS Patients ≥70years were treated less often with concurrent cisplatin dosed every 3weeks (25.5% vs. 71.4%, respectively) and more often with weekly carboplatin (31.9% vs. 3.4%) than patients <70years (n=322; p<0.001). Patients ≥70years experienced increased toxicity during treatment with more frequently hospitalizations (36.2% vs. 21.1%; p=0.02) and a lower rate of PEG removal at last follow-up or death (77.1% vs. 92.9%; p=0.004). A higher proportion of patients ≥70years died within 3months (12.8% vs. 2.8%; p=0.001) following CRT. Patients ≥70 had an increased risk of death at 3months following CRT (odds ratio 5.19, 95% CI 1.64-16.41; p=0.005) and worse survival over time (hazard ratio 2.30, 95% CI 1.34-3.93; p=0.002). CONCLUSIONS Patients ≥70years were more often treated with less toxic chemotherapy, yet experienced higher rates of hospitalization during treatment and increased rates of acute mortality following CRT. The efficacy of chemoradiotherapy for elderly patients should be evaluated in a prospective setting.

Salivary Duct Carcinoma of the Parotid Outcomes with a Contemporary Multidisciplinary Treatment Approach

Objective Salivary duct carcinoma (SDC) is a rare and aggressive malignancy for which an optimal treatment algorithm is lacking. We endeavored to assess the current treatment outcomes for SDC with a multimodality treatment approach combining surgery with adjuvant radiotherapy ± concurrent chemotherapy. Study Design Case series with chart review. Setting A National Cancer Institute–designated comprehensive cancer center. Subjects and Methods The clinical record of 17 patients with salivary duct carcinoma were analyzed to assess locoregional control, recurrence-free survival, and overall survival. Results All SDC cases (n = 17) were managed with surgical resection, followed by adjuvant radiotherapy (47.1%) or concurrent chemotherapy and radiotherapy (52.9%). Median patient follow up was 37 months. An aggressive disease course was generally observed, with 3-year recurrence-free survival and overall survival of 34.4% and 35.5%, respectively. The majority of recurrences were distant. Intensification with adjuvant concurrent chemotherapy was not associated with improved outcomes on univariate survival analysis. Conclusion For salivary duct carcinoma, a multimodality treatment approach is associated with acceptable locoregional control rates but poor distant control and overall survival. Novel systemic therapies may be needed to optimize clinical outcomes.

Hypermetabolism on (18)F-Fluorodeoxyglucose Positron Emission Tomography Scan Does Not Influence the Interpretation of Thyroid Cytopathology, and Nodules with a SUVmax <2.5 Are Not at Increased Risk for Malignancy.

BACKGROUND Hypermetabolism of thyroid nodules on (18)F-fluorodeoxyglucose positron emission tomography (PET) is associated with a higher prevalence of malignancy. However, the definition of hypermetabolism and its impact on cytological interpretation are unclear. METHODS Medical records of all patients with thyroid nodules who had undergone cytological evaluation at the Moffitt Cancer Center between October 2008 and May 2014 were retrospectively reviewed. Those with a PET scan performed within one year of the cytology composed the study group, and the rest were used as controls. The distribution of the cytological categories, percentage of resection, and prevalence of malignancy among each Bethesda category was compared between both groups. RESULTS Fifteen percent (436) of all thyroid nodules with cytological evaluation were in the study group. Maximum standardized uptake values (SUVmax) were directly associated with the probability of having a malignant or a follicular neoplasm cytological diagnosis; and inversely associated with the probability of having a benign cytological diagnosis. However, the prevalence of cancer within each Bethesda category was not associated with SUVmax values. It was found that the prevalence of malignant cytology increased to >5% with SUVmax values ≥2.5. SUVmax values were significantly higher in malignant than in benign nodules on histology (mean values 10.8 vs. 5) but with significant overlap between both groups for either the whole cohort or nodules with indeterminate cytology only limiting its use for differential diagnosis. CONCLUSIONS The prevalence of malignancy in thyroid nodules with a SUVmax <2.5 is similar to the general population, and management should not be modified in those patients. The increased prevalence of malignancy among hypermetabolic thyroid nodules (SUVmax ≥2.5) is well characterized by cytology and does not impact the interpretation of cytological categories. Therefore, SUVmax value does not add relevant information once cytology is available.

Outcomes of mucosal melanoma of the head and neck

Mucosal melanoma of the head and neck is a rare disease with limited data available on outcomes; therefore, we reviewed our institutional experience.