This article summarizes the systemic treatment options for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, with an emphasis on recommendations based on phase II and III comparison trials of commercially available agents. Many single-agent and combination regimens have activity against these cancers, but improvement in overall survival remains a challenge, and median survivals in this population with best available therapy remain less than 1 year. The major recent advancement has been the introduction of epidermal growth factor receptor inhibitors, with mixed success. Although single-agent treatment with methotrexate, paclitaxel, docetaxel, or 5-fluorouracil remains one standard for many patients, the use of cisplatin- or carboplatin-based multidrug regimens that include cetuximab has become more popular, primarily based on one randomized study demonstrating a modest survival improvement of approximately 3 months associated with the addition of cetuximab. The burdensome adverse event profile of multidrug regimens makes appropriate patient selection for such aggressive treatment challenging, and consideration should include factors such as need for palliation, performance status of the patients, history of prior treatment, convenience, and cost. Genetically targeted and immunologically mediated treatments are promising but remain experimental. Given the worrisome prognosis for these patients, innovative clinical trials are a good option for many patients and deserve support.
David M. Brizel, William Lydiatt, and A. Dimitrios Colevas
Head and neck cancer (HNC) is a heterogeneous combination of various sites and types of disease. This manuscript elaborates on 3 important and current issues: the emerging role of human papilloma virus (HPV) in oropharyngeal cancer (OPC), current considerations in systemic therapy for advanced disease, and evolving treatment of the neck. Exogenous carcinogens, most notably tobacco, have classically been implicated in the development of HNC. A large increase in the incidence of OPC has occurred in the past few decades, predominantly in nontobacco users, and is caused by HPV. This disease is unique in many respects and presents an opportunity for novel therapeutic approaches. Because the prognosis for HPV-related HNC is better, regardless of whether surgery or radiation is used as the primary therapy, the reduction of treatment-related morbidity has assumed increasing importance and provides unique opportunities and challenges for de-escalation of therapies. Radiotherapy (RT) and concurrent cisplatin is the most commonly used nonsurgical platform for locally advanced disease. New data suggest that viable alternatives exist to the typical 3 cycles of bolus high-dose cisplatin. The role of RT and concurrent taxanes remains less understood. Similarly, the value of integrating epidermal growth factor inhibition and concurrent chemoradiation is under continuing investigation. The use of PET scanning is changing the traditional use of adjuvant neck dissection after RT or chemoradiation. Recent data support the use of surgery in the presence of a positive posttreatment PET, and observation in the setting of a negative posttreatment scan.
Michael Xiang, A. Dimitrios Colevas, F. Christopher Holsinger, Quynh-Thu X. Le, and Beth M. Beadle
Background: For definitive chemoradiotherapy (chemoRT) of head and neck squamous cell carcinoma (HNSCC), cisplatin is the preferred concurrent agent, with superiority over cetuximab for HPV-associated oropharyngeal squamous carcinoma recently shown in 2 randomized trials (RTOG 1016 and De-ESCALaTE). Patients who are not candidates for cisplatin may be treated with carboplatin instead, but its comparative efficacy is unclear. We analyzed nationwide patterns of care and cancer-specific outcomes after cisplatin- versus carboplatin-based chemoRT. Patients and Methods: Patients with locoregionally advanced (stages III–IVB according to the 6th and 7th editions of the AJCC Cancer Staging Manual) squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received definitive radiotherapy (RT) were identified in the linked SEER-Medicare database. The concurrent chemotherapy regimen was determined through corresponding Medicare claims. Death caused by HNSCC (cancer-specific mortality [CSM]) was analyzed with competing risks. Propensity score analysis and multivariable Fine-Gray regression were used to adjust for baseline differences, including age and comorbidity. Results: We identified 807 patients who received cisplatin-based chemoRT and 342 who received carboplatin-based chemoRT. Most carboplatin recipients (68%) had combination chemotherapy, predominantly with paclitaxel. Carboplatin- and cisplatin-based chemoRT had similar incidences of death attributable to HNSCC (3-year CSM, 29% vs 26%; P=.19), which persisted in propensity score–matched analysis. In addition, no significant difference in overall survival was seen in the matched cohorts. ChemoRT with either cisplatin or carboplatin was superior to RT alone and RT with concurrent cetuximab. In the multivariable model, the adjusted hazard ratio of CSM for carboplatin relative to cisplatin was 1.01 (95% CI, 0.79–1.28; P=.94). Conclusions: Definitive carboplatin-based chemoRT was equivalent to cisplatin-based therapy and superior to RT alone and RT with concurrent cetuximab. In light of recent results of the RTOG 1016 and De-ESCALaTE trials, our findings suggest that carboplatin-based regimens warrant prospective investigation as an alternative to cisplatin for patients who are not cisplatin candidates.
A. Dimitrios Colevas, John J Park, Bruno Fang, Jiang Shao, Lance U'Ren, Jared Odegard, Indu Lal, Minh Phan, Kyaw Z. Thein, and Douglas Adkins
Razelle Kurzrock, A. Dimitrios Colevas, Anthony Olszanski, Wallace Akerley, Carlos L. Arteaga, William E. Carson III, Jeffrey W. Clark, John F. DiPersio, David S. Ettinger, Robert J. Morgan Jr, Lee S. Schwartzberg, Alan P. Venook, Christopher D. Gocke, Jonathan Tait, and F. Marc Stewart
Background: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. Methods: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. Results: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, “molecular profiling/diagnostics” was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory. Conclusions: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care.
David G. Pfister, Kie-Kian Ang, David M. Brizel, Barbara A. Burtness, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks Jr., Ying J. Hitchcock, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Sandeep Samant, Giuseppe Sanguineti, David E. Schuller, Jatin P. Shah, Sharon Spencer, Andy Trotti III, Randal S. Weber, Gregory T. Wolf, and Frank Worden
David G. Pfister, Sharon Spencer, David M. Brizel, Barbara Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks Jr, Ying J. Hitchcock, Antonio Jimeno, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Cristina P. Rodriguez, Sandeep Samant, David E. Schuller, Jatin P. Shah, Randal S. Weber, Gregory T. Wolf, Frank Worden, Sue S. Yom, Nicole R. McMillian, and Miranda Hughes
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to “Principles of Radiation Therapy” for each site and “Principles of Surgery,” and the addition of a new section on “Principles of Dental Evaluation and Management.”
David G. Pfister, Kie-Kian Ang, David M. Brizel, Barbara Burtness, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks Jr., Ying J. Hitchcock, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Sandeep Samant, Giuseppe Sanguineti, David E. Schuller, Jatin P. Shah, Sharon Spencer, Andrea Trotti III, Randal S. Weber, Gregory Wolf, and Frank Worden
David G. Pfister, Kie-Kian Ang, David M. Brizel, Barbara A. Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks Jr, Ying J. Hitchcock, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Sandeep Samant, David E. Schuller, Jatin P. Shah, Sharon Spencer, Randal S. Weber, Gregory T. Wolf, Frank Worden, Sue S. Yom, Nicole R. McMillian, and Miranda Hughes
These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).
David G. Pfister, Sharon Spencer, David Adelstein, Douglas Adkins, Yoshimi Anzai, David M. Brizel, Justine Y. Bruce, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, David W. Eisele, Moon Fenton, Robert L. Foote, Thomas Galloway, Maura L. Gillison, Robert I. Haddad, Wesley L. Hicks Jr., Ying J. Hitchcock, Antonio Jimeno, Debra Leizman, Ellie Maghami, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, James W. Rocco, Cristina P. Rodriguez, Jatin P. Shah, Randal S. Weber, Gregory Weinstein, Matthew Witek, Frank Worden, Sue S. Yom, Weining Zhen, Jennifer L. Burns, and Susan D. Darlow
Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.