Katharine A. Price

Current Treatment Options for Metastatic Head and Neck Cancer

Opinion statementHead and neck squamous cell carcinoma is now the 8th most common cancer affecting men in the United States largely due to a rising epidemic of oropharynx cancer (tonsil and tongue base) associated with the human papillomavirus (HPV). The median overall survival for recurrent or metastatic head and neck cancer (R/M HNSCC) remains less than 1 year despite modern chemotherapy and targeted agents. Palliative chemotherapy and the epidermal growth factor receptor inhibitor, cetuximab, constitute the backbone of treatment for patients with R/M HNSCC. Platinum doublets studied in phase III trials include cisplatin/5-FU, cisplatin/paclitaxel, and cisplatin/pemetrexed. Platinum chemotherapy in combination with 5-fluorouracil and cetuximab has resulted in the longest median overall survival. Combination platinum regimens increase response rates and toxicity but not survival and should be reserved for patients who are symptomatic from their disease for whom the benefit of a partial response may be worth the cost of increased treatment-related side effects. For many patients who are asymptomatic with a low disease burden, single agent regimens are appropriate to balance treatment with side effects. Drugs commonly used as single agents in the treatment of R/M HNSCC include docetaxel, paclitaxel, cetuximab, capecitabine, pemetrexed, and methotrexate. Best supportive care alone is often appropriate for poor performance status patients. Palliative radiation therapy is beneficial for treating symptomatic metastatic sites. Aggressive symptom management is imperative for all patients and often should include referral to experts in palliative care and pain management. New therapies currently under investigation include mTOR inhibitors, anti-angiogenic agents, and IGF1R inhibitors. Given the poor prognosis for most patients with R/M HNSCC, enrollment in clinical trials investigating novel approaches to therapy should be encouraged.

Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma.

OBJECTIVES Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent. This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16-positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose or weekly cisplatin. MATERIALS AND METHODS Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients. RESULTS 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p=0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p=0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p=0.56), and 3-year recurrence free survival of 84% and 82% (p=0.93). Extracapsular extension did not affect prognosis in either group. CONCLUSIONS No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be a better treatment for patients with HPV-positive oropharynx cancer to preserve survival and minimize toxicity.

Mechanisms of and therapeutic approaches for overcoming resistance to epidermal growth factor receptor (EGFR)-targeted therapy in squamous cell carcinoma of the head and neck (SCCHN).

The majority of squamous cell carcinoma of the head and neck (SCCHN) overexpress epidermal growth factor receptor (EGFR), which has been associated with poor treatment response and survival. However, only modest success has been achieved with the use of single agents that target EGFR, possibly due to primary and acquired resistance. This review will discuss key mechanisms of and therapeutic approaches to overcoming resistance to EGFR-targeted therapy in SCCHN. Recent preclinical and clinical investigations have demonstrated that other ErbB family receptors (eg, HER2 and HER3) and other horizontal resistance mechanisms, as well as activation of downstream signaling pathways, epigenetic events, and nuclear EGFR, are possible mediators of resistance to anti-EGFR therapeutics. Key downstream pathways that may be implicated in EGFR resistance include phosphatidylinositol-3-kinase/protein kinase B, vascular endothelial growth factor (VEGF), and mammalian target of rapamycin (mTOR). Multiple agents that target EGFR and other ErbB family members (ie, lapatinib, afatinib, and dacomitinib), as well as combination therapies that target EGFR and selected other pathways (eg, VEGF, mTOR, and c-Met) are being investigated clinically. In addition, several phase II and III trials continue to investigate strategies to enhance the efficacy of EGFR-targeted therapy in SCCHN.

Risk factors for locoregional relapse after transoral robotic surgery for human papillomavirus–related oropharyngeal squamous cell carcinoma

Factors predicting locoregional relapse after surgery for oropharyngeal squamous cell carcinoma (SCC) were identified in the pre‐human papillomavirus (HPV) era. We examined whether traditional indications for adjuvant radiotherapy (RT) or adjuvant chemoradiotherapy (CRT) still correlate with locoregional relapse in HPV‐positive patients after transoral robotic surgery (TORS).

High-grade transformation of acinic cell carcinoma: an inadequately treated entity?

OBJECTIVE Acinic cell carcinoma (AcCC) is an uncommon salivary gland malignancy. We aim to characterize the clinical and pathologic characteristics of AcCC with and without high-grade transformation (HGT). Importantly, cases of mammary analogue secretory carcinoma, a recently described histologic mimic of AcCC, have been excluded by using cytogenetics and molecular studies. STUDY DESIGN Archival surgical pathology material was obtained for patients diagnosed with AcCC at Mayo Clinic Rochester between 1990 and 2010. Tumors harboring the ETV6-NTRK3 fusion transcript were excluded from analysis by using cytogenetics and molecular studies. Tumors with HGT were characterized by areas with an infiltrative growth pattern, nuclear anaplasia, prominent nucleoli, brisk mitotic activity, geographic necrosis, and stromal desmoplasia. Demographic and clinical data were extracted from the medical records. RESULTS AcCC with HGT was seen in 8 of 48 cases (17%). Patients with AcCC with HGT were significantly older than patients without HGT (median 69 vs 54 years; P = .04). Angiolymphatic invasion was more common in AcCC with HGT (P = .02). Relapse-free survival and overall survival were significantly worse for cases of AcCC with HGT (hazard ratio 10.4 and 9.3, respectively; P < .0001 for both comparisons). Locoregional recurrence-free survival was not significantly different (P = .12), but distant metastases-free survival was significantly worse in patients with HGT compared with non-HGT patients (P < .0001). CONCLUSIONS Prognosis for overall survival and distant relapse for AcCC patients with HGT is significantly worse than that for patients without HGT.

Concurrent Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx in a Married Couple

Background. Although alcohol and tobacco use are known risk factors for development of squamous cell carcinoma in the head and neck, human papillomavirus (HPV) has been increasingly associated with this group of cancers. We describe the case of a married couple who presented with HPV-positive oropharynx squamous cell carcinoma within two months of each other. Methods. Tumor biopsies were positive for p16 and high-risk HPV in both patients. Sanger sequencing showed a nearly identical HPV16 strain in both patients. Both patients received chemoradiation, and one patient also underwent transoral robotic tongue base resection with bilateral neck dissection. Results. Both patients showed no evidence of recurrent disease on follow-up PET imaging. Conclusions. New head and neck symptoms should be promptly evaluated in the partner of a patient with known HPV-positive oropharynx cancer. This case expands the limited current literature on concurrent presentation of HPV-positive oropharynx squamous cell carcinoma in couples.

Acinic cell carcinoma of the salivary gland with metastatic spread to the pancreas.

Metastatic disease to the pancreas is rare among solid tumors and has not been well described for salivary cancers. We report a patient who developed an isolated metastatic lesion in the pancreas from acinic cell carcinoma of the salivary gland, presenting as acute pancreatitis.

A Pilot Study Comparing FLT-PET and FDG-PET in the Evaluation of Response to Cetuximab and Radiation Therapy in Advanced Head and Neck Malignancies

Background: We prospectively compared FLT-PET and FDG-PET in evaluating response to cetuximab and chemoradiotherapy for HNSCC. Methods: Six patients with HNSCC received cetuximab followed by chemoradiotherapy. Patients had FLTand FDG-PET scans at baseline, after cetuximab, and 2 weeks into chemoradiotherapy. Changes in SUVmax on successive scans were compared to baseline. Results: After induction therapy, changes in SUVmax ranged from -2 to 32% for FLT-PET and -24 to 0% for FDGPET. After two weeks of chemoradiotherapy, changes in SUVmax ranged from -71 to 9% for FLT-PET and -80 to -7% for FDG-PET. One patient experienced consecutive increases in FLT uptake not detected by FDG-PET. No patient recurred at a median 14.6 months. Conclusions: Functional imaging early during definitive therapy for HNSCC is feasible. Similar changes in FLT and FDG uptake are detected during chemoradiotherapy; however, distinct differences were seen after induction cetuximab therapy. Further follow-up will facilitate correlation of radiotracer uptake with clinical outcome.

Characteristics and long-term outcomes of head and neck squamous cell carcinoma after solid organ transplantation

INTRODUCTION Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients with post-transplant HNSCC are unknown. MATERIALS AND METHODS We retrospectively identified patients who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and adequate follow up were included. Median overall survival and progression free survival were analyzed using the Kaplan-Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. RESULTS Thirty-three patients met study inclusion criteria. The median time to diagnosis of HNSCC after transplant was 5.9years. The primary site was oral cavity in 15 patients, oropharynx in 10, larynx in 3, hypopharynx in 2, parotid in 2 and unknown in 1 patient. Eighty-eight percent underwent upfront surgical resection. Of those, sixty-six percent received adjuvant therapy. Six percent of patients had definitive chemoradiation. Treatment was well tolerated and did not lead to graft rejection. The 5-year overall survival rate was 45% and 37% for localized and locally advanced disease respectively. Seventy-five percent of patients with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year overall survival rate of 67%). In multivariate analysis, age ≥60years was a negative predictor of survival (HR 2.7; 95% CI, 1.1-6.5; P=0.03). CONCLUSIONS Patients with post-transplant HNSCC have relatively poor survival and high risk of locoregional and distant recurrence. HPV- positive oropharyngeal tumors continue to have better outcomes in this population.

Integrative medicine in cancer survivors

Purpose of review Due to medical advances and an aging population, the number of cancer survivors continues to rise. Survivors often experience late and long-term sequelae of cancer and its treatment (e.g., fatigue, pain, fear of recurrence, and stress). As a result, some patients have utilized or expressed interest in integrative medicine (IM) modalities for prevention of recurrence, optimizing health, enhancing quality of life, and managing symptoms. The purpose of this review is to focus on research published during the past year that informs our understanding of the utility of IM for cancer survivors. Recent findings Physical activity, diet, dietary supplements, mind–body modalities, acupuncture, and massage therapy all may play a role in the management of the physical (e.g., fatigue and pain) and emotional (e.g., anxiety and fear) issues faced by cancer survivors. Summary IM therapies are appealing to and utilized by many cancer survivors and may reduce symptom burden. Clinicians who provide cancer survivorship care may improve patient care by understanding the evidence for and against their use.