Rapid development and use of patient-specific ctDNA biomarkers to avoid a "rash decision" in an ovarian cancer patient.

Epithelial ovarian cancer (OvCa) is the most lethal female reproductive tract malignancy. A major clinical hurdle in patient management and treatment is that when using current surveillance technologies 80% of patients will be clinically diagnosed as having had a complete clinical response to primary therapy. In fact, the majority of women nonetheless develop disease recurrence within 18 mo. Thus, without more accurate surveillance protocols, the diagnostic question regarding OvCa recurrence remains framed as "when" rather than "if." With this background, we describe the case of a 61-yr-old female who presented with a 3-mo history of unexplained whole-body rash, which unexpectedly led to a diagnosis of and her treatment for OvCa. The rash resolved immediately following debulking surgery. Nearly 1 yr later, however, the rash reappeared, prompting the prospect of tumor recurrence and requirement for additional chemotherapy. To investigate this possibility, we undertook a genomics-based tumor surveillance approach using a targeted 56-gene NGS panel and biobanked tumor samples to develop personalized ctDNA biomarkers. Although tumor-specific TP53 and PTEN mutations were detectable in all originally collected tumor samples, pelvic washes, and blood samples, they were not detectable in any biosample collected beyond the first month of treatment. No additional chemotherapy was given. The rash spontaneously resolved. Now, 2 yr beyond the patient's original surgery, and in the face of continued negative ctDNA findings, the patient remains with no evidence of disease. As this single case report suggests, we believe for the first time that ctDNA can provide an additional layer of information to avoid overtreatment.

Nodal Metastases in Acinic Cell Carcinoma of the Parotid Gland.

The objective of this study was to evaluate the clinical outcome of patients with acinic cell carcinomas of the parotid gland after elective neck dissection (END). A retrospective chart review was performed including 66 patients with acinic cell carcinoma of the parotid gland. Clinical parameters were retrieved and statistically analyzed regarding disease-free survival (DFS) and disease-specific survival (DSS). An END was done in 27 (40.9%) patients, and occult metastases were detected in 4 (14.8%) patients of whom three were low-grade carcinoma. Positive neck nodes were associated with significantly worse DSS (p = 0.05). Intermediate and high-grade carcinoma (HR 8.62; 95% confidence interval (CI): 1.69-44.01; p = 0.010), perineural invasion (HR 19.6; 95%CI: 0.01-0.37; p = 0.003) and lymphovascular invasion (HR 10.2; 95%CI: 0.02-0.59; p = 0.011) were worse prognostic factors for DFS. An END should be considered in patients with acinic cell carcinoma of the parotid gland due to (i) a notable rate of occult neck metastases in low-grade tumors and (ii) the worse DSS of patients with positive neck nodes.

Progressive tumefactive fibroinflammatory lesion of the infratemporal fossa treated by radiation therapy.

Tumefactive fibroinflammatory lesion (TFIL) is a rare benign tumor in the head and neck region. We present a case of a 40-year-old female with a benign but progressive lesion of the infratemporal fossa, which was diagnosed as TFIL. Patient responded briefly to a course of steroid treatment but eventually showed progression and was unresponsive to further steroids. She was then treated with external beam radiation to a dose of 60 Gy in 30 fractions. After radiation a slow, gradual decrease in tumor size was noted over the course of years and she is free of disease after more than 11 years of follow-up. The major long-term side effect this patient developed was an expected unilateral radiation-induced retinopathy, due to the close proximity of the lesion to the orbit. The dilemma of treatment of benign disease with radiation with potential long-term complications is discussed and a review of the literature on TFIL is presented.

A population-based study of factors associated with early versus late stage oral cavity cancer diagnoses.

Oral cavity cancers can be detected early yet many are diagnosed with advanced disease. We assessed risk factors for advanced stage disease in a population-based study. Study population was all Ontario patients with anterior tongue or floor of mouth cancers diagnosed between 1991 and 2000 (n=2033). Data are from a retrospective chart review. Risk factors included: demographic characteristics, co-morbidity, precancerous lesions, dental status, smoking, alcohol use, and social marginalization. Multivariate regression analyses assessed independent associations while controlling for disease grade and site. Forty percent had advanced disease. Eighty-nine percent presented with symptoms and 66% were referred by a family physician. Risk factors in the tongue group were being: age ≥80 (RR 1.47), widowed (RR 1.34), social marginalized (RR 1.69), a current smoker (RR 1.26), or a smoker-heavy drinker (RR 1.73). Risk factors in the floor of mouth group were being: age ≥70 (70-79: RR 1.24 and ≥80: RR 1.43), and socially marginalized (RR 1.22). Having a pre-cancerous lesion (RR 0.44) or a regular dentist (RR 0.84) was protective in the floor of mouth group. Risk factors for those with co-morbid illnesses were being: age ≥70 (70-79: RR 1.28 and ≥80: RR 1.55), separated/divorced (RR 1.26), socially marginalized (RR 1.37), or a smoker-heavy drinker (RR 1.44); while having a regular dentist was protective (RR 0.83). Targeted education to alert those at risk about oral cancer warning signs and better training coupled with opportunistic oral cavity exams by family physicians could reduce the burden of this disease.

A dose escalation study of hyperfractionated accelerated radiation delivered with integrated neck surgery (HARDWINS) for the management of advanced head and neck cancer.

BACKGROUND AND PURPOSE: To determine toxicity and outcome of radiation dose escalation with hyperfractionated accelerated radiation delivered with neck surgery (HARDWINS) for head and neck cancer. PATIENTS AND METHODS: Patients with stage III and IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx were enrolled. Dose levels of 60, 62 and 64Gy were delivered with twice daily fractionation in 40 fractions over 4 weeks. Involved and at-risk nodal regions received microscopic dose (46.5-48Gy) with neck dissection for node positive patients 8 weeks after radiation. RESULTS: One hundred and sixty-nine patients were enrolled (60Gy n=22, 62Gy n=26, 64Gy n=121). No grade 4 acute toxicity was observed. Incidence of acute grade 3 toxicity was: skin (2%), larynx (6%), pharynx and esophagus (66%) and mucous membrane (75%). Feeding tube dependence was observed in 14% of patients receiving 64Gy. Overall survival, and relapse free rate at 5 years were 65% and 63%, respectively. Local, nodal and distant relapse free rates at 5 years were 77%, 94% and 81% (median follow-up 3.8 years). CONCLUSIONS: HARDWINS can be delivered without acute grade 4 toxicity but significant grade 3 acute toxicity. A significant proportion of the patients have prolonged swallowing dysfunction. Outcomes suggest this regimen represents an alternative to chemoradiation.

A comparison of published head and neck stage groupings in laryngeal cancer using data from two countries.

The combination of T, N, and M classifications into stage groupings is meant to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. We tested the UICC/AJCC fifth edition stage grouping and six other TNM-based groupings proposed for head and neck cancer for their ability to meet these expectations in laryngeal cancer using data from Ontario, Canada, and the area of Southern Norway surrounding Oslo. We defined four criteria to assess each grouping scheme: (1) the subgroups defined by T, N, and M comprising a given group within a grouping scheme have similar survival rates (hazard consistency); (2) the survival rates differ among the groups (hazard discrimination); (3) the prediction of cure is high (outcome prediction); and (4) the distribution of patients among the groups is balanced. We previously identified or derived a measure for each criterion, and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). The data sets were population-based, with 861 cases from Ontario and 642 cases from Southern Norway. Clinical stage assignment was used and the outcome of interest was cause-specific survival. Summary scores across the seven schemes had similar ranges: 0.9 to 5.1 in Ontario and 1.8 to 5.7 in Southern Norway, but the ranking varied. Summing the scores across the two datasets, the TANIS-7 scheme (Head & Neck 1993;15:497-503) ranked first, and was ranked high in both datasets (first and second, respectively). The UICC/AJCC scheme ranked sixth out of seven schemes, and its ranking was fifth and seventh, respectively. UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform best. Our results suggest that the usefulness of the TNM system could be enhanced by optimizing the design of stage groupings through empirical investigation.