Krzysztof Misiukiewicz

A Systematic Review of Head and Neck Cancer Quality of Life Assessment Instruments

Although quality of life (QOL) is an important treatment outcome in head and neck cancer (HNC), cross-study comparisons have been hampered by the heterogeneity of measures used and the fact that reviews of HNC QOL instruments have not been comprehensive to date. We performed a systematic review of the published literature on HNC QOL instruments from 1990 to 2010, categorized, and reviewed the properties of the instruments using international guidelines as reference. Of the 2766 articles retrieved, 710 met the inclusion criteria and used 57 different head and neck-specific instruments to assess QOL. A review of the properties of these utilized measures and identification of areas in need of further research is presented. Given the volume and heterogeneity of QOL measures, there is no gold standard questionnaire. Therefore, when selecting instruments, researchers should consider not only psychometric properties but also research objectives, study design, and the pitfalls and benefits of combining different measures. Although great strides have been made in the assessment of QOL in HNC and researchers now have a plethora of quality instruments to choose from, more work is needed to improve the clinical utility of these measures in order to link QOL research to clinical practice. This review provides a platform for head and neck-specific instrument comparisons, with suggestions of important factors to consider in the systematic selection of QOL instruments, and is a first step towards translation of QOL assessment into the clinical scene.

Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus–Related Oropharyngeal Carcinoma

IMPORTANCE Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear. OBJECTIVE To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study. MAIN OUTCOMES AND MEASURES Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis. RESULTS Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months. CONCLUSIONS AND RELEVANCE Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

Early Detection of Recurrent Disease by FDG-PET/CT Leads to Management Changes in Patients With Squamous Cell Cancer of the Head and Neck

OBJECTIVE The objective of this study was to compare the efficacy of surveillance high-resolution computed tomography (HRCT) and physical examination/endoscopy (PE/E) with the efficacy of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/HRCT for the detection of relapse in head and neck squamous cell carcinoma (HNSCC) after primary treatment. METHODS This is a retrospective analysis of contemporaneously performed FDG-PET/HRCT, neck HRCT, and PE/E in 99 curatively treated patients with HNSCC during post-therapy surveillance to compare performance test characteristics in the detection of early recurrence or second primary cancer. RESULTS Relapse occurred in 19 of 99 patients (20%) during a median follow-up of 21 months (range: 9-52 months). Median time to first PET/HRCT was 3.5 months. The median time to radiological recurrence was 6 months (range: 2.3-32 months). FDG-PET/HRCT detected more disease recurrences or second primary cancers and did so earlier than HRCT or PE/E. The sensitivity, specificity, and positive and negative predictive values for detecting locoregional and distant recurrence or second primary cancer were 100%, 87.3%, 56.5%, and 100%, respectively, for PET/HRCT versus 61.5%, 94.9%, 66.7%, and 93.8%, respectively, for HRCT versus 23.1%, 98.7%, 75%, and 88.6%, respectively, for PE/E. In 19 patients with true positive PET/HRCT findings, a significant change in the management of disease occurred, prompting either salvage or systemic therapy. Of the 14 curatively treated patients, 11 were alive with without disease at a median follow-up of 31.5 months. CONCLUSION FDG-PET/HRCT has a high sensitivity in the early detection of relapse or second primary cancer in patients with HNSCC, with significant management implications. Given improvements in therapy and changes in HNSCC biology, appropriate modifications in current post-therapy surveillance may be required to determine effective salvage or definitive therapies.

Radiographic extracapsular extension and treatment outcomes in locally advanced oropharyngeal carcinoma

Pathologic extracapsular extension (pECE) in metastatic lymph nodes is associated with poor prognosis for oropharyngeal carcinoma. The prognostic value of radiographic extracapsular extension (rECE) has not been studied.

Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer.

Recent Phase III data presented at the American Society of Clinical Oncology (ASCO) 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA) approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials.

Organ Preservation for Adenoid Cystic Carcinoma of the Larynx

OBJECTIVES Two cases of adenoid cystic carcinoma (ACC) of the larynx were treated with chemoradiotherapy (CRT) for organ preservation. We reviewed case series and current literature to contrast the potential role of primary CRT as an organ-sparing modality with standard laryngectomy and radiotherapy in patients with laryngeal ACC. METHODS Two treatment-naïve patients with laryngeal ACC treated at Dana-Farber Cancer Institute between 2002 and 2007 were identified. Both patients were offered standard laryngectomy followed by adjuvant radiotherapy or organ-sparing treatment modality. RESULTS Both patients were males, aged 57 and 73. The patients completed a course of combined chemoradiotherapy with weekly carboplatin and paclitaxel and 7-8 weeks of radiotherapy to a total dose of 6,600 and 7,000 cGy over 50 and 57 days, respectively. There were no treatment breaks or delays because of toxicity. The major toxicities reported by both patients, as anticipated, were Grade 3 mucositis, desquamative dermatitis, and severe dysphagia, all of which resolved. Both patients are alive with local regional control and functional larynx; one at 112+ months with pulmonary metastases at 54 months, and the other disease free at 60+ months. CONCLUSIONS Definitive chemoradiation with weekly carboplatin and paclitaxel may be a potential alternative to the current standard of surgery and radiation for patients with locally advanced laryngeal ACC who request an organ-sparing approach. In this group of patients, salvage laryngectomy may be reserved for those who are locally recurrent or chemoradiotherapy resistant. Although CRT provided long-term local regional control in our two patients, there are evident limitations in obtaining evidence for a determination of treatment of rare diseases. This report provides support for following an organ preservation plan in selected patients.

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

OBJECTIVES Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. MATERIALS AND METHODS 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. RESULTS At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p=0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR]=1.81, 95%CI=0.47-6.92). CONCLUSION This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation.

The use of induction chemotherapy prior to chemoradiation for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains controversial. We explored whether toxicity from induction chemotherapy influenced the delivery of concurrent chemoradiation. Among 171 consecutive previously unirradiated patients with HNSCC treated with combined chemotherapy and radiation, we identified 66 patients with stage III-IVB head and neck carcinoma who were treated with induction chemotherapy prior to planned chemoradiation. The most common induction regimen was docetaxel, cisplatin and 5-FU (TPF; 80%) for 2 to 3 cycles. Mean radiation dose was 72 Gy (range, 36-75 Gy). Concurrent chemotherapy regimens included cisplatin (26%), cetuximab (5%) and 5-fluorouracil/hydroxyurea (65%)-based regimens. At a median follow-up of 27 months (range, 9-56 months), the 2-year locoregional control and distant control rates were 85 and 86%, respectively. The 2-year disease-free survival and overall survival rates were 74 and 80%, respectively. Although there were no grade 5 toxicities during induction chemotherapy, 26% of patients required hospitalization for adverse events, including 5% needing intensive care. The most common high grade adverse events were grade 4 neutropenia (21%) and neutropenic fever (17%). Six percent of patients were unable to tolerate concurrent chemotherapy. The 2-year disease-free survival was significantly higher in patients able to complete induction and concurrent chemoradiation as planned (83 vs. 27%, p<0.001). Induction chemotherapy followed by concurrent chemoradiation results in promising survival rates in our cohort of advanced head and neck carcinoma patients. Due to severe toxicities in a subset of patients, this strategy is only recommended in selected high-risk patients who are carefully followed by an experienced multidisciplinary team.

Tolerability, Toxicity, and Temporal Implications of Transoral Robotic Surgery (TORS) on Adjuvant Radiation Therapy in Carcinoma of the Head and Neck

Objectives: Overall treatment package time (from surgery to radiotherapy [RT] completion) > 100 days can portend poor outcomes in head and neck cancer. Faster postoperative recovery seen with transoral robotic surgery may decrease treatment duration and toxicity for adjuvant RT and chemoradiation. Methods: We retrospectively reviewed all patients treated with transoral robotic surgery (n = 124) and adjuvant RT and chemoradiation (n = 33) at our institution for head and neck cancer from April 2007 to December 2011 to determine treatment duration, acute toxicity, and long-term percutaneous gastric tube rates. Results: The median overall treatment time was 86 days and from surgery to RT start was 41 days; median RT duration was 44 days. No wound breakdown or infection occurred during or after RT. Two-year actuarial locoregional control, distant metastasis–free survival, and overall survival rates were 93%, 96%, and 97%, respectively. Conclusions: Adjuvant RT after transoral robotic surgery for head and neck cancer can be completed safely and in a timely fashion. Longer follow-up and a larger cohort will be needed to determine if this regimen is more effective than traditional surgery followed by adjuvant RT.

Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non–human papillomavirus16 viral subtypes

The majority of human papillomavirus (HPV)‐related oropharyngeal carcinomas (OPCs) are associated with HPV genotype 16; however, OPC can be associated with other high‐risk non‐HPV16 genotypes.