Search

Objective The primary course of treatment for patients with low- to intermediate-risk tonsil cancer has evolved with a shift toward primary transoral robotic surgery (TORS) or radiation therapy (RT). While favorable outcomes have been reported after deintensification via unilateral TORS or RT (uniRT), comparisons of functional outcomes between these treatments are lacking. We compared clinical outcomes (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] and feeding tube [FT]) and patient-reported swallowing outcomes (MD Anderson Dysphagia Inventory [MDADI]) based on primary treatment strategy: TORS, uniRT, or bilateral RT (biRT). Study design Secondary analysis of prospective cohort. Setting Single institution. Methods The study sample comprised 135 patients with HPV/p16+ T1-T3, N0-2b (American Joint Committee on Cancer, seventh edition), N0-1 (eighth edition) squamous cell carcinoma of the tonsil were sampled from a prospective registry. Modified barium swallow studies graded per DIGEST, FT placement and duration, and MDADI were collected. Results Baseline DIGEST grade significantly differed among treatment groups, with higher dysphagia prevalence in the TORS group (34%) vs the biRT group (12%, P = .04). No significant group differences were found in DIGEST grade or dysphagia prevalence at subacute and longitudinal time points (P = .41). Mean MDADI scores were similar among groups at baseline (TORS, 92; uniRT, 93; biRT, 93; P = .90), subacute (TORS, 83; uniRT, 88; biRT, 82; P = .38) and late time points (TORS, 86; uniRT, 86; biRT, 87; P = .99). FT placement and duration significantly differed among primary treatment groups (FT [median days]: TORS, 89% [3]; uniRT, 8% [82]; biRT, 37% [104]; P Conclusion While TORS and uniRT offer optimal functional outcomes related to dysphagia, results suggest that no measurable clinician-graded or patient-reported differences in swallow outcomes exist among these primary treatment strategies and biRT. Aside from baseline differences that drive treatment selection, differences in FT rate and duration by primary treatment strategy likely reflect diverse toxicities beyond dysphagia.

BACKGROUND Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established. METHODS The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence. RESULTS In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS. CONCLUSIONS In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings.

Author(s): Saiyed, Faiez K; Guo, Theresa; Johnson, Faye; Myers, Jeffrey N | Abstract: BackgroundOutcomes of oropharyngeal squamous cell carcinoma (OPSCC) after development of distant metastases (DM) in the context of human papillomavirus (HPV) tumor status remain controversial in the literature.MethodsOPSCC patients with DM treated between June 2015 and March 2019 were included from a prospectively enrolled database. Characteristics of DM including sites, episodes, and timing of disease were analyzed in addition to survival after DM.ResultsSixty-nine HPV-positive and 18 HPV-negative OPSCC patients with DM were included. The 2-year survival after DM was higher for HPV-positive patients (54.0% vs. 11.3%, pnl 0.001). HPV-positive patients did not demonstrate greater episodes or sites of DM. Multiple sites of DM, early development of DM, and Charlson comorbidity Index were independently associated with worse survival after DM.ConclusionsWhile multiple sites, early DM, and comorbidities were poor prognostic factors, OPSCC patients with distant progression can have substantial survival after DM, including M1 patients.

Objectives Evaluate the use of induction chemotherapy (IC) in oropharyngeal cancer (OPC) and its impact on subjective functional outcomes using a validated MD Anderson Symptom Inventory‐Head and Neck (MDASI‐HN) survey tool. Methods A single institution retrospective review of OPC patients who received IC, including reasons given for using IC, regimens employed, responses, and patient‐reported outcomes (PRO). The latter included pain, distress, dysphagia, xerostomia, and feeding tube placement and dependency. PRO's were assessed using the validated MD Anderson Symptom Inventory‐Head and Neck (MDASI‐HN) conducted at baseline, during treatment, and at six‐month follow up. Results One hundred and twenty‐five patients were evaluable. They were more likely to have large primary and/or bulky or low neck nodal disease as a reason for IC. A taxane‐containing regimen was most common. Primary tumor response was seen in 83.2% and the nodal response in 81.6%. Pain and xerostomia improved with IC, dysphagia was not adversely affected with IC. These symptoms all increased with consolidation chemoradiotherapy (CRT) but returned to baseline by 6 months post treatment. Feeding tube placement did not increase with IC but did with CRT, most patients were no longer feeding tube dependent at 6 months. Conclusion This retrospective review of subjective functional outcomes, especially swallowing and feeding tube dependency, using the MDASI survey tool in 125 oropharyngeal cancer patients with large primary tumors and/or bulky adenopathy treated predominantly with platinum‐taxane based induction chemotherapy showed that such outcomes were not adversely impacted. While not standard, such approach may be beneficial in such patients. Level of Evidence 2., HPV‐positive oropharyngeal cancer typically has a good survival prognosis. Standard treatment with radiation and chemotherapy, while curative, can produce long term dysfunctional outcomes. Induction chemotherapy has not been shown to improve overall survival but is occasionally used in patients with high stage and/or aggressive disease. we looked at the impact of induction chemotherapy on subjective functional outcomes.

Background Cutaneous squamous cell carcinoma (CSCC) is a very common malignancy in which most patients present with localized disease. Recurrent and metastatic disease is rare, and there is no standard therapy. These tumors frequently overexpress the epidermal growth factor receptor (EGFR). We conducted a phase 2 trial to determine the response rate to therapy with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with locoregionally recurrent or metastatic CSCC that was not amenable to curative treatment (NCT01198028). Methods Eligible patients had CSCC not amenable to curative intent therapy. Patients who had previously received anti-EGFR targeted therapy were excluded. All patients received oral therapy with erlotinib 150 mg daily. Response was assessed every 8 weeks, and treatment continued until progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was overall response rate according to RECIST 1.1 criteria. Results A total of 39 patients received treatment during the trial; 29 of these patients were evaluable for response. The overall response rate was 10% (3/29); all responses were partial responses. The disease control rate (partial response + stable disease) was 72% (21/29). The median progression-free survival was 4.7 months (95% confidence interval, 3.5-6.2 months); the median overall survival was 13 months (95% confidence interval, 8.4-20.5 months). No unexpected toxicities were seen. Conclusion Erlotinib therapy was feasible for most patients with incurable CSCC and was associated with expected toxicities. However, only a modest response rate of 10% was observed. Further study of EGFR tyrosine kinase inhibitors in this patient population is not warranted. Cancer 2018;124:2169-73. © 2018 American Cancer Society.

Background There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx. Methods This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis. Results Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity. Conclusions Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society.

Background We focused on a cohort of radiation naive patients who had recurrent oral cavity cancer (recurrent OCC) to assess their outcomes with salvage multimodal therapy. Methods A retrospective single institutional study was performed of patients with recurrent OCC. Disease recurrence and survival outcomes were assessed. Results Seventy-eight patients were analyzed. All patients had salvage surgery and intensity-modulated radiotherapy (IMRT) and 74% had chemotherapy. Five-year overall survival, recurrence-free survival, and locoregional control rates were 59%, 60%, and 74%, respectively. Conclusion Outcomes of radiation naive patients with recurrent OCC are fair, and seem similar with patients with locally advanced nonrecurrent OCC treated with multimodal therapy. © 2016 Wiley Periodicals, Inc. Head Neck 39: 633–638, 2017

BACKGROUND Favorable outcomes for human papillomavirus–associated oropharyngeal cancer have led to interest in identifying a subgroup of patients with the lowest risk of disease recurrence after therapy. De-intensification of therapy for this group may result in survival outcomes that are similar to those associated with current therapy but with less toxicity. To advance this effort, this study analyzed the outcomes of oropharyngeal cancer patients treated with or without systemic therapy. METHODS This was a retrospective study of patients with oropharyngeal cancer treated between 1985 and 2012. The criteria for inclusion were ≤10 pack-years of cigarette smoking and stage III/IVA cancer limited to T1-3, N1-N2b, and T3N0 disease. A survival analysis was performed with the primary endpoint of progression-free survival (PFS). RESULTS The cohort included 857 patients. Systemic therapy was given to 439 patients (51%). The median survival was 80 months. The 2-year PFS rate was 91%. When the analysis was limited to 324 patients irradiated without systemic therapy, the 2- and 5-year PFS rates were 90% and 85%, respectively. Furthermore, for these 324 patients, the 5-year PFS rates for T1, T2, and T3 disease were 90%, 83%, and 70%, respectively. The 5-year PFS rate for patients treated with systemic therapy for T3 disease was 77% (P = .07). CONCLUSIONS According to the low-risk definition currently established in cooperative trials, the patients had a 2-year PFS rate approximating 90%. When patients who were treated with radiation alone were evaluated, no compromise was observed in this high rate of PFS, which is higher than the 2-year PFS thresholds used in current cooperative trials. Cancer 2016. © 2016 American Cancer Society.

Background This was a retrospective study of patients with human papillomavirus (HPV)-associated oropharyngeal cancer treated with concurrent systemic therapy and radiation. Methods Data were extracted through chart review, and statistical analyses included frequency tabulation, chi-square, and Kaplan–Meier tests. Results Three hundred thirty-nine patients were analyzed; 166 received neoadjuvant chemotherapy. One hundred thirty-six patients were treated with cisplatin, 123 with cetuximab, and 59 with carboplatin. The 2-, 3-, and 5-year actuarial overall survival rates were 92%, 88%, and 78%, respectively. There were no significant differences in survival or disease control when analyzed by systemic agent. Platin-treated patients had greater hematologic toxicity, and required more intravenous hydration. The incidence of confluent mucositis was highest among patients treated with cetuximab. Conclusion Platin and cetuximab seem to have similar efficacy when delivered concurrently with radiation in our retrospective population study. Although platin did cause greater hematologic toxicity, radiation-specific side effects seemed relatively comparable. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Background Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare cancer of thymic origin with little information available for treating clinicians. Methods We performed a comprehensive literature search and updates were requested from all authors. We report one recent case. Results We present the most comprehensive review of the clinical literature for SETTLE. We identified 41 published cases. SETTLE usually presents as an asymptomatic neck mass. Most patients successfully underwent surgical resection of the primary tumor. The mean latency to develop metastasis was 10 years. SETTLE is uniformly responsive to radiotherapy and combination chemotherapy in the rare cases where response data are available. Conclusion Although SETTLE is initially indolent, it has the capacity to metastasize late in its course. The malignant potential of this tumor might be underestimated because of the lack of long-term follow-up. In cases in which complete surgical resection is not possible, radiotherapy or combination chemotherapy is effective. © 2014 Wiley Periodicals, Inc. Head Neck 37: 746–754, 2015

BACKGROUND: Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting. METHODS: Patients with recurrent and/or metastatic HNSCC after platinum-based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG). Primary endpoints were 12-week progression-free survival (PFS) and objective response rate with a 2-stage design and early withdrawal if the 12-week PFS rate was ≤20% and no patients had an objective response (OR). Forty-nine serum cytokines and angiogenic factors (CAFs) were analyzed from treated patients. RESULTS: Of the 15 patients enrolled, 12 were evaluable for response, and all patients were evaluable for toxicity. No OR was observed and 2 patients (16.7%) had stable disease (SD) at 8 weeks. The median treatment duration was 59 days, the median time to disease progression was 3.9 weeks, and the median survival was 26 weeks. One patient required a dose reduction, 3 patients required dose interruptions, and 4 patients were hospitalized for toxicity. Dasatinib inhibited c-Src both when administered orally and via PFG. Greater mean drug exposure, decreased half-life, and greater maximum concentration were observed in patients receiving dasatinib via PFG. Eleven baseline CAFs were associated with treatment outcome and 1 CAF, macrophage migration inhibitory factor, was found to be differentially modulated in correlation with SD versus disease progression. CONCLUSIONS: Single-agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite c-Src inhibition. The toxicity profile was consistent with that reported in other solid tumors, and the drug can be given via PFG tube. Cancer 2011. © 2010 American Cancer Society.

BACKGROUND: The recently developed the Src and Abelson (Abl) kinase inhibitor dasatinib has antitumor effects in epithelial and mesenchymal tumors. Preclinical data have indicated that dasatinib is metabolized primarily through cytochrome P450 3A4 (CYP3A4) and may cause QT prolongation. In light of its improved tolerability, the authors were interested in the safety of a once-daily dasatinib regimen. METHODS: The authors conducted a phase 1 trial of dasatinib in 29 patients with advanced solid tumors. Segment 1 of the trial was short term and sequential and was designed to determine whether the coadministration of the potent CYP3A4 inhibitor ketoconazole had an effect on the pharmacokinetics of dasatinib. Segment 2 was designed to evaluate the safety of dasatinib as dosing was increased. QT intervals were monitored closely in both segments. Efficacy was assessed in Segment 2 using both positron emission tomography and computed tomography. RESULTS: Hematologic toxicities were markedly less than those observed in patients with leukemia, whereas nonhematologic toxicities were similar. The authors determined that the maximum recommended dose was 180 mg once daily based on the incidence of pleural effusion. Coadministration of ketoconazole led to a marked increase in dasatinib exposure, which was correlated with an increase in corrected QT (QTc) values of approximately 6 msec. No adverse cardiac events were observed. CONCLUSIONS: The dose-limiting toxic effect for dasatinib was pleural effusion. The pharmacokinetic and cardiac studies indicated that coadministration of dasatinib with potent CYP3A4 inhibitors or agents that prolong the QTc interval should be avoided if possible. Close monitoring for toxicity and dose reduction should be considered if the coadministration of such agents cannot be avoided. Cancer 2010. © 2010 American Cancer Society.

BACKGROUND Epithelial–mesenchymal transformations (EMT) are critical for the invasion, progression, and metastasis of epithelial carcinogenesis. The role of EMT in head and neck squamous carcinoma (HNSC) tumorigenesis remains unexplored. In the current study, the expressions of several factors associated with the induction of EMT in HNSC cell lines and tumor specimens were investigated to define their functional and pathologic role in HNSC. METHODS Eleven HNSC cell lines and 50 primary tumor tissue specimens formed the materials of this study. Western blot analysis as well as immunohistochemical, and functional techniques were used to assess the status of activated Src (p-Src), E-cadherin, and vimentin in both cell lines and tumor tissues and the results were correlated with patients' clinicopathologic parameters. RESULTS The results demonstrated the inverse expression of p-Src and E-cadherin in the majority of cell lines and in primary tumor tissues compared with normal squamous mucosa. Elevated levels of p-Src were accompanied by down-regulation of E-cadherin and the expression of vimentin in epithelial tumor cells. In vitro inhibition of Src led to E-cadherin reexpression and increased cell contact in squamous carcinoma cell lines. Immunophenotypic analysis of these markers in primary tumor tissues demonstrated a significant correlation between increased p-Src, decreased E-cadherin, and vimentin expression and aggressive tumor features including penetrating invasive fronts, high-grade sarcomatoid transformation, and lymph node metastasis. CONCLUSIONS The results of the current study indicate that Src and E-cadherin may play an important role in EMT, invasion, and aggressive clinicopathologic features of HNSC. These proteins may be targeted for the therapeutic intervention of patients with HNSC. Cancer 2008. © 2008 American Cancer Society.

BACKGROUND: Irinotecan has significant activity in small-cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte–colony-stimulating factor (G-CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC. METHODS: A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G-CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G-CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1-year survival rate. RESULTS: Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade ≥2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression-free and overall survivals were 6.0 months and 10.9 months, respectively. The 1-year survival rate was 33%. CONCLUSIONS: Weekly therapy with IP alternating with EP and G-CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression-free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society.