Prognostic impact of retropharyngeal lymphadenopathy in early-stage HPV-associated oropharyngeal cancer: Implications for staging optimization.

OBJECTIVES: We analyzed the prognostic impact of retropharyngeal lymphadenopathy (RPL) in stage I node-positive HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: We performed a centralized and blinded radiographic review of the pre-treatment images of 234 consecutive patients with AJCC 8th edition stage I cT1-2N1 HPV-associated OPSCC treated with definitive chemoradiation from 2006 to 2016. Five-year disease control and survival outcomes were reported. The prognostic significance of RPL was evaluated through multivariable analysis adjusting for age, smoking history (<10 vs. >10 pack-years), and systemic regimen received. RESULTS: Median follow-up for surviving patients was 49 months (range: 16-121). RPL was associated with increased locoregional recurrence (LRR) (17.0% v. 3.4%, p = 0.01) and distant metastasis (DM) (29.1% v. 5.9%, p = 0.001) and inferior progression-free survival (PFS) (55.6% v. 88.2%, p < 0.001) and overall survival (OS) (60.6% v. 91.2%, p < 0.001). In stage I patients who did not receive high-dose cisplatin (HDC), RPL was associated with worse LRR (p = 0.04), DM (p = 0.03), PFS (p < 0.001), and OS (p < 0.001), whereas in those who did receive HDC, RPL was only associated with increased DM (p = 0.002) and inferior PFS (p = 0.04). CONCLUSION: This study suggests that RPL portends a poor prognosis in stage I node-positive HPV-associated OPSCC. The negative impact on LRR may have been mitigated by receipt of HDC. Outcomes of stage I disease with RPL were comparable to historical reports of patients with more advanced-stage disease. Incorporation of RPL into future disease staging should be considered in order to optimize risk-stratification and exclude unsuitable candidates from treatment de-intensification efforts.

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer.

OBJECTIVE: We compared high-dose cisplatin (HDC) vs. triweekly carboplatin (TC)-based chemoradiation in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A retrospective review was conducted from 2006 to 2015 of 421 patients with locally advanced p16-positive OPSCC receiving definitive radiotherapy concurrent with 3 cycles of HDC (100 mg/m2, n = 230) or TC (AUC = 5, n = 191). Three-year locoregional recurrence (LRR), distant metastasis (DM), overall recurrence rate (ORR), overall survival (OS), and cause-specific survival (CSS) are reported. HDC and TC were compared accounting for age, sex, comorbidity index score, smoking history, T stage, and N stage. RESULTS: For all-comers, no difference was observed between HDC and TC for any outcome except for ORR which was lower in patients receiving HDC (12% vs. 17%, p = 0.03). On stage-based analysis, no difference was observed between agents for any outcome for stage I or II disease. However, patients with stage III disease receiving HDC had lower rates of LRR (9% vs. 21%, p = 0.03), DM (7% vs. 28%, p = 0.006), and ORR (14% vs. 40%, p = 0.002), and superior OS (89% vs. 78%, p = 0.04) and CSS (95% vs. 80%, p = 0.02). Patients receiving HDC experienced higher rates of grade 3 leukopenia (25% vs. 11%, p < 0.001), weight loss ≥20% from baseline (21% vs. 8%, p < 0.001), and gastrostomy-tube placements (66% vs. 27%, p < 0.001). CONCLUSION: TC demonstrated comparable outcomes to HDC for stage I or II HPV-associated OPSCC but was inferior to HDC for stage III disease. TC was associated with less toxicity and may be a potential de-intensification agent for early-stage disease.

Impact of chemotherapy regimen on treatment outcomes in patients with HPV-associated oropharyngeal cancer with T4 disease treated with definitive concurrent chemoradiation.

OBJECTIVES: Although human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is typically associated with a good prognosis, patients with T4 disease experience relatively high rates of treatment failure. Our aim was to identify predictors of relapse among patients with clinical T4 disease. MATERIAL & METHODS: A retrospective review was conducted of 93 consecutive patients who underwent definitive concurrent chemoradiation for HPV-associated OPSCC with clinical T4 disease from July 2006 to December 2015. Three-year outcomes, including locoregional recurrence (LRR), distant metastasis (DM), overall survival (OS), and cancer-specific survival (CSS), were examined and reported from the date of treatment completion. Multivariable analysis using a Cox proportional hazards model was performed to test associations between outcome and patient and disease characteristics as well as chemotherapy regimen (high-dose cisplatin (HDC) vs. other). RESULTS: Median follow-up for surviving patients was 50 months (range 18-133). For all-comers, 3-year rates of LRR, DM, OS, and CSS were 15%, 19%, 79%, and 86%, respectively. On multivariable analysis, the only factor prognostic for patient outcomes was the chemotherapy regimen. For patients who received HDC vs. an alternative regimen, 3-year LRR, DM, OS, and CSS, were 9% vs. 20% (p = 0.09), 10% vs. 28% (p = 0.04), 89% vs. 67% (p = 0.04), and 96% vs. 77% (p = 0.02), respectively. CONCLUSION: In patients with HPV-associated OPSCC bearing clinical T4 disease, receipt of a concurrent systemic agent other than HDC resulted in increased treatment failure and inferior survival. This analysis suggests that HDC should remain the preferred concurrent regimen for these patients.

Induction chemotherapy followed by concurrent chemoradiation versus concurrent chemoradiation alone in the definitive management of p16-positive oropharyngeal squamous cell carcinoma with low-neck or N3 disease.

OBJECTIVE: The addition of induction chemotherapy (ICT) to concurrent chemoradiation (CCRT) has been investigated as a method of improving outcomes among patients with locally advanced head and neck squamous cell carcinoma. Previous studies have consisted of heterogeneous populations with both p16-positive and p16-negative disease and varying extent of nodal disease burden. We evaluated the role of ICT in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) at high-risk of distant failure. MATERIALS AND METHODS: A retrospective review was conducted of 88 consecutive patients with p16-positive OPSCC with low-neck and/or N3 lymphadenopathy. Among these patients, 44 received ICT followed by CCRT, and 44 received CCRT alone with concurrent agents including Cisplatin, Carboplatin, and Cetuximab. Disease control and survival outcomes were reported after adjusting for age, T stage, N stage, and smoking status. RESULTS: Median follow-up for surviving patients was 47 (range: 13-115) months. Patients who received CCRT alone were older than those who received ICT (61 years vs. 56 years; p = 0.02); the groups were otherwise similarly balanced. 3-year distant metastasis: 38% vs. 18% (adjusted hazard ratio (HR) = 0.32 [0.13-0.82]; p = 0.02). 3-year progression-free survival: 49% vs. 74% (adjusted HR = 0.46 [0.22-0.93]; p = 0.03). 3-year overall survival: 67% vs. 83% (adjusted HR = 0.48 [0.21-1.12]; p = 0.09). CONCLUSION: Among patients with p16-positive OPSCC with low-neck and/or N3 lymphadenopathy, ICT followed by CCRT may reduce the risk for distant failure over CCRT alone and lead to improved progression-free survival. Future trials should concentrate on patients at the highest risk of distant metastasis in order to appropriately assess the benefit of ICT.

Concurrent Radiotherapy and Triweekly Carboplatin for the Definitive Treatment of Locally Advanced Laryngeal Carcinoma.

PURPOSE OF THE STUDY: In 2003, our institution adopted triweekly carboplatin (tCb) area under the curve (AUC) 5 as an alternative to high-dose cisplatin (100 mg/m) for select patients receiving definitive concurrent chemoradiation for locally advanced laryngeal carcinoma (LALC). Here, we present our experience and outcomes with this definitive concurrent chemoradiation regimen. METHODS: From January 2003 through December 2013, 53 patients with stage III (60%) or IVA (40%) LALC were treated with tCb AUC 5 and concurrent radiotherapy to 70 Gy without neoadjuvant chemotherapy. Reasons for using carboplatin instead of cisplatin in these patients were: age 70 and older (21%), poor renal function (6%), presence of 1 or more major comorbid condition(s) (36%), and per discretion of the treating medical oncologist (38%). Primary disease site was glottis in 22 (42%) patients and supraglottis in 31 (58%) patients. RESULTS: Median follow-up time was 63 months for surviving patients. Out of the 53 patients, 43 (81%) received all 3 cycles of carboplatin and all patients received their intended dose of radiotherapy. Although 17 (32%) patients required a feeding tube during treatment, only 2 (4%) required it long term. There were no acute treatment-related grade 4 or 5 hematologic toxicities. On last follow-up, 14 (26%) patients had died of intercurrent disease. For the subgroup of "RTOG 9111 eligible" patients in our cohort (n=46), 5-year estimates of overall survival, disease-free survival, laryngectomy-free survival, larynx preservation, and locoregional control were: 49%, 42%, 39%, 80%, and 63%, respectively. CONCLUSIONS: In patients with LALC who are suboptimal candidates for high-dose cisplatin, our experience suggests that tCb AUC 5 with concurrent radiotherapy provides acceptable outcomes with tolerable toxicity.

Nonsecretory multiple myeloma.

Nonsecretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma (MM) and accounts for 1% to 5% of all cases of MM. The clinical presentation and radiographic findings of NSMM and MM are the same. The diagnosis of MM requires the detection of a monoclonal gammopathy in the serum or urine. In NSMM, however, no such gammopathy can be demonstrated, making the diagnosis more difficult. We describe a 43-year-old African American woman who initially had back pain and pathologic vertebral compression fractures that were thought to be due to osteoporosis. Five months later, hypercalcemia developed and NSMM was diagnosed. No monoclonal gammopathy was found in the serum or urine, but skeletal survey showed diffuse osteolytic lesions, and bone marrow biopsy revealed marked plasmacytosis. The immunohistochemical techniques and chromosomal analysis methods that are currently available are discussed.