LS16031305 The Management of s With r. Lin Learning Objectives: 1. To understand the changing demographics of oropharynx cancer, and the impact of human papillomavirus on overall survival and the patterns of relapse in patients with oropharynx cancer. 2. To understand the standard surgical approach to early-stage oral cavity cancer 3. To understand the indications for postoperative chemoradiation for head and neck cancer. 4. To understand current standard of care approach to locally-advanced nasopharynx cancer 5. To understand the indications and options for larynx preservation in patients with locally-advanced larynx cancer. Question 1: For patients with HPV-positive, advanced-stage disease who receive curative-intent therapy, which patients are at highest risk of disease recurrence, and what is the predominant form of disease recurrence? a) Advanced T-stage and N-stage, locoregional recurrence b) Advanced T-stage, systemic recurrence c) Advanced T-stage and N-stage, systemic recurrence d) Advanced N-stage, locoregional recurrence C In patients with HPV-positive oropharynx cancer treated with definitive intent radiotherapy, bulky disease (either T4 or N3) places patients into the high-risk category. For these patients, the 3-year outcomes are 76% for distant control and 82% for locoregional control. This is contrasted against much higher rates 93% distant control and 95% locoregional control for patients who fall into the low-risk category (T1-3, N0-N2c). O Sullivan B, Huang SH, Siu LL, et al. eintensification Candidate Subgroups in Human Papillomavirus-Related Oropharyngeal Cancer According to Minimal Risk of istant Metastasis. J ClinOncol 31; 543-550. - - - End of Question 1 - - - -
Question 2: In a patient diagnosed with an early-stage oral cavity squamous cell carcinoma, the optimal course of initial treatment would consist of: a) Radiotherapy alone b) Surgery for the primary site alone (omitting neck dissection) c) Surgery for the primary site alone, followed by radiotherapy to the neck d) Surgery for the primary site + neck dissection For oral cavity cancers, the treatment of choice is for an upfront surgical approach. efinitive radiotherapy is reserved only for cases that are surgically unresectable and/or patients who are medically inoperable. The optimal surgery is for resection of the primary site as well upfront elective neck dissection, which has been demonstrated to yield superior disease-free and overall survival when compared to surgery to the primary site alone and performing neck dissection only at the time of recurrence for purposes of salvage. Cruz AK, Vaish R, Kapre N, et al. Elective versus Therapeutic Neck issection in Node-Negative Oral Cancer. N Engl J Med 2015; 373: 521-9. - - - End of Question 2 - - -
Question 3: A 49-year-old Caucasian female is diagnosed with a clinical stage 3, T1N2M0, keratinizing squamous cell carcinoma of the nasopharynx. What is the optimal treatment for her stage and diagnosis? a) Radiotherapy alone b) Concurrent chemoradiation, omitting adjuvant chemotherapy c) Sequential therapy, with radiotherapy alone followed by adjuvant chemotherapy d) Concurrent chemoradiation, with adjuvant chemotherapy The results of the randomized intergroup 0099 study, as well as multiple randomized trials from Asia all confirm a survival benefit of concurrent chemoradiation to RT alone. The Intergroup study treated with concurrent chemoradiation, followed by adjuvant chemotherapy, and this regimen remains the standard of care in a nonendemic population. A recent randomised study did not show a statistically significant benefit to the addition of chemotherapy, but this trial was performed in an endemic population, and may not apply to a non-endemic population. 1) Al-Sarraf M, LeBlanc M, Giri PGS, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized Intergroup Study 0099. J ClinOncol 1998; 16: 1310-17. 2) Chen L, Hu C-S, Chen X-Z, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharygeal carcinoma: a phase 3 multicentrerandomised controlled trial. - - - End of Question 3 - - -
Question 4: A 60-year-old male with a 40 pack-year smoking history is newly diagnosed with a stage 4a, T3 (fixed vocal cord), N2c (bilateral neck nodes), M0 squamous cell carcinoma of the larynx. He declines upfront surgical therapy, which would require total laryngectomy, and elects organ preservation. Which treatment regimen is optimal for larynx preservation, and constitutes current standard of care for this diagnosis. B a) Altered fractionation radiotherapy alone b) Concurrent cisplatin and radiotherapy c) Standard fraction radiotherapy alone d) Sequential chemotherapy and radiation (induction cisplatin + fluorouracil followed by radiotherapy) RTOG 91-11 was a randomized trial of organ preservation for locally-advanced larynx cancer comparing 3 treatments: standard fraction radiotherapy alone versus radiotherapy with concurrent cisplatin versus induction cisplatin + fluorouracil followed by radiotherapy. Both the initial and long-term results demonstrate that concurrent chemoradiotherapy was superior to the other 2 treatment arms with respect to laryngeal preservation. 1) Forastiere AA, Goepfert H, Maor M, et al. Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer. N Engl J Med 2003; 349: 2091-8. 2) Forastiere AA, Zhang Q, Weber RS, et al. Long-Term Results of RTOG 91-11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients with Locally Advanced Larynx Cancer. INCOMPLETE REFERENCE - - - End of Question 4- - -
Question 5: If the patient with larynx cancer described in question 6 was instead diagnosed with T4a disease (disease penetrating through thyroid cartilage), with N2c disease, what would be the optimal treatment approach? a) isease is unresectable, and therefore treat with concurrent chemotherapy and radiation, per the RTOG 91-11 b) isease is resectable, but treat with organ preservation concurrent chemotherapy and radiation, per the RTOG 91-11. c) Surgery alone d) Surgery + adjuvant RT (+/- chemotherapy, as clinically indicated) T4n a disease is technically resectable (T4b is unresectable). The RTOG 91-11 listed T4a disease where disease penetrated through the thyroid cartilage as an exclusion criteria, and therefore, the results of this study supporting concurrent cisplatin and radiotherapy is not therefore applicable to this patient. Surgery alone is not standard of care in this situation, as all patients who underwent total laryngectomy in the VA larynx study were treated with adjuvant RT. The correct answer, therefore, is surgery + adjuvant RT. 1) The epartment of Veteran Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991; 324: 1685-90. 2) Forastiere AA, Goepfert H, Maor M, et al. Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer. N Engl J Med 2003; 349: 2091-8. 3) Grover S, Swisher-McClure S, Mitra N, et al. Total laryngectomy versus larynx preservation for T4a larynx cancer: Patterns of care and survival outcomes. Int J RadiatOncolBiolPhys 2015; 92: 594-601. - - - End of Question 5- - -