Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated.

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Conventional radiotherapy alone in treatment of unresectable or locally advanced head and neck cancer has poor results. To improve outcome without significant increase in acute and late morbidity, we began a moderately accelerated hyperfractionation radiation therapy protocol without breaks for treatment of unresectable/advanced head and neck malignancies. From August 1984 to June 1995, 48 patients with unresectable or advanced carcinoma of the head and neck were treated using a protocol of accelerated hyperfractionation radiation therapy at Kaiser Permanente Medical Center, Los Angeles. Patients were treated twice a day using 150 cGy per fraction, 4 days per week, to a final dose of 60 Gy. Two patients were excluded from this analysis because they did not complete treatment. With a median follow-up of 33 months, 31 (67%) patients have had disease recurrence, 30 (65%) of whom had a locoregional component to their failures. At the last follow-up, 12 patients (26%) were alive with no evidence of disease, 30 patients had died of disease, and 4 had died of intercurrent disease without recurrence. Nine (19%) patients required treatment interruptions averaging 8 days in duration. This accelerated regimen resulted in outcomes similar to those with conventional radiotherapy, most likely because of a conservative total dose. Further refinement of fractionation schedules with potential incorporation of chemotherapy must be investigated.

The AJCC eighth edition cancer staging manual consolidates all patents with p16+ oropharyngeal cancer with unilateral nodal disease no larger than 6cm in size within the new clinical N1 group. The new classification system comprises a heterogeneous group of disease with varying radiographic findings. Our objective was to identify the radiographic characteristics which may portend a poor prognosis. Materials/Methods: We conducted a central radiological review of the staging imaging studies of patients who underwent upfront definitive concurrent chemoradiation for p16+ oropharyngeal cancer from May 2006 to September 2015. Pathology review was performed of all cases with standardized p16 reporting. All patients had at least an MRI or CT scan for review; 52% also had PET scans. Nodal stage was confirmed or corrected through central radiographic investigation. Per AJCC 8 th edition staging criteria, 230 patients had stage I (cT1-2N1) disease and were included for analysis. Image findings analyzed included the largest node size, location/ level of involved node(s), overt radiographic extracapsular extension (ORECE), presence or absence of matted lymphadenopathy, and predominant appearance of involved nodes (solid, cystic, or both). Results: Median follow-up for surviving patients was 40 [12-115] months. Median age was 61 [35-81] years. For the entire cohort, 3-year progression-free survival (PFS) and overall survival (OS) were 86% and 89%, respectively. On multivariate analysis, ORECE (HR Z 2.73 [1.13-6.60], P Z 0.03), retropharyngeal (RP) involvement (HR Z 3.19 [1.30-7.86], P Z 0.01), and low-neck involvement (level IV and/or Vb) (HR Z 4.15 [1.58-10.93], P Z 0.004) were statistically significant predictors for poorer PFS. Of note, no recurrences were observed in patients with predominantly cystic nodes (n Z 37). Low-neck involvement was also a significantly poor prognostic factor for OS (HR Z 4.72 [1.53-14.61], P Z 0.007), whereas RP involvement trended toward poorer OS but did not reach significance (HR Z 2.82 [0.98-8.13], P Z 0.06). Conclusion: This analysis involving central assessment of nodal radiographic prognostic factors for stage I p16+ oropharyngeal carcinoma validates the new clinical N1 classification system by confirming no prognostic impact for size; however, additional image findings within this cohort negatively impacted outcomes. The presence of low-neck disease, RP adenopathy, and ORECE were associated with statistically significant worse PFS. Low-neck involvement was also a statistically significant predictor for inferior OS in these patients. We believe caution is advised against de-intensification efforts in stage I patients with these factors. Interestingly, no treatment failures were observed in patients with predominantly cystic nodes, however intercurrent disease death may have precluded a significant prognostic impact of this factor on multivariate analysis.

Purpose/Objective(s): Although Triweekly Cisplatin-based concurrent chemoradiation has recently been shown to be superior to Cetuximabbased concurrent therapy in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) in multiple randomized trials, the optimal concurrent agent in those who are poor candidates for Cisplatin is unknown. Here we report the cancer control and survival outcomes in this cohort of patients who underwent radiotherapy concurrent with either triweekly Carboplatin or weekly Cetuximab at our institution. Materials/Methods: A retrospective review was conducted from November 2006 through September 2016 of patients with non-metastatic p16-positive OPSCC who underwent definitive intensity modulated radiotherapy to a median dose of 70 Gy (range 66-70 Gy) concurrent with weekly Cetuximab (n Z 40) per Bonner protocol or triweekly Carboplatin (AUC Z 5) (n Z 191). No patient received accelerated radiotherapy. Patients receiving induction chemotherapy or oncological surgery of any kind prior to concurrent therapy were excluded. All patients had stage conversion according to the AJCC 8 th Edition Cancer Staging Manual. Three-year locoregional recurrence (LRR), distant metastasis (DM), overall recurrence rate (ORR), overall survival (OS), and cause-specific survival (CSS) are reported. Cetuximab and Carboplatin groups were compared accounting for age, sex, smoking history, T stage, and N stage. Results: Patients who received Carboplatin were younger (median age 62 vs. 70, P<0.001). The Cetuximab group had a higher percentage of patients with >10 pack-years of smoking (57% vs. 37%, P<0.02). The two cohorts were otherwise well-balanced with respect to other baseline patient and disease characteristics including T and N stage. After a median follow up of 40 months for surviving patients, those receiving Carboplatin had lower 3-year rates of LRR (8% vs. 16%, p Z 0.02), DM (11% vs. 21%, p Z 0.01), and ORR (17% vs. 29%,p Z 0.008), and superior OS (90% vs. 63%, p Z 0.003) and CSS (93% vs. 77%, p Z 0.01). Conclusion: Our study suggests that, if medically feasible, triweekly Carboplatin concurrent with radiotherapy should be preferred to that with cetuximab in patients with p16+ OPSCC who are not eligible to receive cisplatin as it results in superior cancer control and survival outcomes.