The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or ...radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking.
We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial.
Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (
= .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm
84.8 ± 12.5 in the TORS + ND arm,
= .74; year 3: 88.9 ± 11.3
83.3 ± 13.9,
= .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (
= .015). Dry mouth scores were higher in RT patients over time (
= .041).
On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).
Background
Renaming encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently ...suggested to prevent the overtreatment, cost and stigma associated with this low-risk entity. The purpose of this study is to document the incidence and further assess the clinical outcomes of reclassifying EFVPTC to NIFTP.
Methods
We searched synoptic pathologic reports from a high-volume academic endocrine surgery hospital from 2004 to 2013. The standard of surgical pathology practice was based on complete submission of malignant thyroid nodules along with the nontumorous thyroid parenchyma. Rigid morphological criteria were used for the diagnosis of noninvasive EFVPTC, currently known as NIFTP. A retrospective chart review was conducted looking for evidence of malignant behavior.
Results
One hundred and two patients met the strict inclusion criteria of NIFTP. The incidence of NIFTP in our cohort was 2.1% of papillary thyroid cancer cases during the studied time period. Mean follow-up was 5.7 years (range 0–11). Five patients were identified with nodal metastasis and one patient with distant metastasis. Overall, six patients showed evidence of malignant behavior representing 6% of patients with NIFTP.
Conclusion
Our study demonstrates that the incidence of NIFTP is significantly lower than previously thought. Furthermore, evidence of malignant behavior was seen in a significant number of NIFTP patients. Although the authors fully support the de-escalation of aggressive treatment for low-risk thyroid cancers, NIFTP behaves as a low-risk thyroid cancer rather than a benign entity and ongoing surveillance is warranted.
Purpose This guideline provides recommendations on the management of adults after head and neck cancer (HNC) treatment, focusing on surveillance and screening for recurrence or second primary ...cancers, assessment and management of long-term and late effects, health promotion, care coordination, and practice implications. Methods ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The American Cancer Society (ACS) HNC Survivorship Care Guideline was reviewed for developmental rigor by methodologists. An ASCO Expert Panel reviewed the content and recommendations, offering modifications and/or qualifying statements when deemed necessary. Results The ASCO Expert Panel determined that the ACS HNC Survivorship Care Guideline, published in 2016, is clear, thorough, clinically practical, and helpful, despite the limited availability of high-quality evidence to support many of the recommendations. ASCO endorsed the ACS HNC Survivorship Care Guideline, adding qualifying statements aimed at promoting team-based, multispecialty, multidisciplinary, collaborative head and neck survivorship care. Recommendations The ASCO Expert Panel emphasized that caring for HNC survivors requires a team-based approach that includes primary care clinicians, oncology specialists, otolaryngologists, dentists, and other allied professionals. The HNC treatment team should educate the primary care clinicians and patients about the type(s) of treatment received, the likelihood of potential recurrence, and the potential late and long-term complications. Primary care clinicians should recognize symptoms of recurrence and coordinate a prompt evaluation. They should also be prepared to manage late effects either directly or by referral to appropriate specialists. Health promotion is critical, particularly regarding tobacco cessation and dental care. Additional information is available at www.asco.org/HNC-Survivorship-endorsement and www.asco.org/guidelineswiki .
Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no ...randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment.
The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0–2, and with T1–T2, N0–2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1–2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting.
68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20–33) for the radiotherapy group and 29 months (23–43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six 18% of 34 patients vs none of 34), hearing loss (13 38% vs five 15%), and tinnitus (12 35% vs two 6%) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine 26% vs one 3%). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS.
Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options.
Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.
Background Acute kidney injury (AKI) is common in infants after cardiopulmonary bypass and is associated with poor outcomes. Peritoneal dialysis improves outcomes in adults with AKI after bypass, but ...pediatric data are limited. This retrospective case-matched study was conducted to determine if the practice of peritoneal dialysis catheter (PDC) placement during congenital heart surgery is associated with improved clinical outcomes in infants at high risk for AKI. Methods Forty-two infants undergoing congenital heart surgery with planned PDC placement (PDC+) were age-matched to infants undergoing similar surgery without PDC placement (PDC−). Demographic, baseline and outcome data were compared. Our primary outcome was negative fluid balance on postoperative days 1 to 3. Secondary outcomes included time to negative fluid balance, time to extubation, frequency of electrolyte corrective medications, inotrope scores, and other clinical outcomes. Results Baseline data did not differ between groups. The PDC+ group had a higher percentage of negative fluid balance on postoperative days 1 and 2 (57% vs 33%, P = .04; 85% vs 61%, P = .01). The PDC+ group had shorter time to negative fluid balance (16 vs 32 hours, P < .0001), earlier extubation (80 vs 104 hours, P = .02), improved inotrope scores ( P = .04), and fewer electrolyte imbalances requiring correction ( P = .03). PDC-related complications were rare. Conclusions PDC use is safe and associated with earlier negative fluid balance and improved clinical outcomes in infants at high risk for AKI. Routine PDC use should be considered for infants undergoing cardiopulmonary bypass. Further prospective studies are essential to prove causative effects of PDC placement in this population.
Active surveillance is sometimes considered as a disease management option for individuals with small, low-risk papillary thyroid carcinoma.
To assess whether patient age is associated with ...progression of low-risk papillary thyroid carcinoma (tumor growth or incident metastatic disease) in adults under active surveillance.
Eight electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Emcare, PsycINFO, Web of Science, and ClincalTrials.gov) were searched from inception to March 2019, supplemented with a hand search. Two investigators independently screened citations, reviewed full-text articles, and abstracted data. Additional data were sought from authors. Random-effects meta-analyses were performed using incidence data (statistically adjusted for confounders and crude rates).
A total of 1658 unique citations were screened, and 62 full-text articles were reviewed, including 5 studies. Three studies included exclusively microcarcinomas and 2 included tumors up to 2 cm in maximal diameter. The mean age of participants was 51.0 to 55.2 years in 4 studies reporting this value. The mean or median follow-up was 5 years or more in 3 studies and approximately 2 years in 2 studies. The pooled risk ratio for tumor growth of 3 mm or more in maximal diameter in individuals aged 40 to 50 years compared with younger individuals was 0.51 when adjusted for confounders (95% CI, 0.29-0.89; 1619 patients, 2 studies), and the unadjusted risk ratio of this outcome for individuals 40 years or older was 0.55 (95% CI, 0.36-0.82; 2097 patients, 4 studies). In adults aged 40 to 45 years, the unadjusted risk ratio for any tumor volume increase compared with younger individuals was 0.65 (95% CI, 0.51-0.83; 1232 patients, 4 studies). The pooled risk ratio for incident nodal metastases in individuals 40 years or older was 0.22 (95% CI, 0.10-0.47; 1806 patients, 3 studies); however, in a secondary analysis, the risk difference was not significantly different. There was no statistically significant heterogeneity in any of the meta-analyses. There were no thyroid cancer-related deaths nor incident distant metastases.
This study suggests that older age may be associated with a reduced risk of primary papillary thyroid carcinoma tumor growth under active surveillance. Incident metastatic disease is uncommon during active surveillance.
Tumor thickness (TT) appears to be a strong predictor for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity (OSCC), but a precise clinically optimal TT cutoff point has ...not been established. To address this question, the authors conducted a meta-analysis.
All relevant articles were identified from MEDLINE and EMBASE as well as from cross-referenced publications cited in relevant articles. Lymph-node involvement was confirmed and identified as positive lymph-node declaration (P(LN)D) by either pathologic positivity on immediate neck dissection or by neck recurrence identified after follow-up > or = 2 years. Odds ratios (OR) were calculated to quantify the predictive value of TT. Negative predictive values (and the percentage of patients falsely predicted to not have P(LN)D FN-P(LN)D) were compared to determine the optimal TT cutoff point.
Sixteen studies were selected from 72 potential studies, yielding a pooled total of 1136 patients. Data were examined for the following TT cutoff points: 3 mm (4 studies, 387 patients), 4 mm (9 studies, 778 patients), 5 mm (6 studies, 367 patients), and 6 mm (4 studies, 488 patients). The OR (95% CI) was 7.3 (5.3-10.1) for the overall group. The proportion of FN-P(LN)D was 5.3% (95% CI, 2.0-11.2), 4.5% (2.6-7.2), 16.6% (11.5-22.8), and 13.0% (9.7-16.9) for TT<3, <4, <5, and <6 mm, respectively. There was a statistically significant difference between the 4-mm and 5-mm TT cutoff points (P = .007).
TT was a strong predictor for cervical lymph-node involvement. The optimal TT cutoff point was 4 mm.
Objectives/Hypothesis
To demonstrate the comparative effectiveness of transoral robotic surgery (TORS) to intensity modulated radiotherapy (IMRT) for early T‐stage oropharyngeal cancer.
Data Sources
...The search included MEDLINE, EMBASE, CENTRAL, PsychInfo, CINAHL, and bibliographies of relevant studies through September 2012.
Methods
Studies included patients treated for early T‐stage oropharynx cancer with TORS or IMRT. Study retrieval and data extraction were conducted in duplicate and resolved by consensus. Treatment‐ specific details, as well as recurrence, survival, and adverse events, were collected. Methodologic quality for each study was appraised.
Results
Twenty case series, including eight IMRT studies (1,287 patients) and 12 TORS studies (772 patients), were included. Patients receiving definitive IMRT also received chemotherapy (43%) or neck dissections for persistent disease (30%), whereas patients receiving TORS required adjuvant radiotherapy (26%) or chemoradiotherapy (41%). Two‐year overall survival estimates ranged from 84% to 96% for IMRT and from 82% to 94% for TORS. Adverse events for IMRT included esophageal stenosis (4.8%), osteoradionecrosis (2.6%), and gastrostomy tubes (43%)—and adverse events for TORS included hemorrhage (2.4%), fistula (2.5%), and gastrostomy tubes at the time of surgery (1.4%) or during adjuvant treatment (30%). Tracheostomy tubes were needed in 12% of patients at the time of surgery, but most were decannulated prior to discharge.
Conclusion
This review suggests that survival estimates are similar between the two modalities and that the differences lie in adverse events. Laryngoscope, 124:2096–2102, 2014
Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods ...are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation.
We conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I-IVA human papillomavirus-negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls.
CAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated (
> 0.85). Patients with detectable pretreatment ctDNA by both methods demonstrated significantly worse overall survival (HR = 7.5;
= 0.025) independent of clinical stage, with lack of ctDNA clearance post-treatment strongly correlating with recurrence. We further leveraged cfMeDIP-seq profiles to validate a prognostic signature identified from TCGA samples.
Tumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications.
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