De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer.
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ABSTRACT:
SUBMITTER: An Y
PROVIDER: S-EPMC6460758 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer.
An Yi Y Holsinger F Christopher FC Husain Zain A ZA
Cancers of the head & neck 20161220
Current adjuvant treatment guidelines for oropharyngeal squamous cell carcinoma treated with primary surgery are based on studies that predate the human papillomavirus (HPV) era. HPV-associated oropharynx carcinoma (HPV-OPC) has a much more favorable prognosis compared to HPV-unassociated cancer and is increasingly considered to be a distinct disease entity due to its unique etiology, presentation, and behavior. Currently, there is significant interest in adjuvant treatment de-intensification of ...[more]
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Project description:ObjectivesHuman papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a unique form of head and neck cancer with improved prognosis. We assessed survival for stage I patients with low- or intermediate-risk pathologic features with surgery alone compared with surgery with adjuvant radiation (RT) or chemoradiation (CRT).Materials and methodsWe identified patients with stage I HPV+ OPSCC (after restaging with 8th edition staging system) treated with surgery alone, adjuvant RT or CRT in the National Cancer Data Base from 2010 to 2013. We compared survival for low-risk patients (≤1 metastatic lymph nodes with no adverse features) and intermediate-risk patients (2-4 metastatic lymph nodes, microscopic extranodal extension (ENE) or lymphovascular invasion).ResultsWe examined 1677 patients with median follow-up of 43.9 months. In the intermediate-risk group, 4-year overall survival was 94.0% with surgery alone, 91.5% with adjuvant RT and 92.0% with adjuvant CRT (p = 0.72). There were similar rates of overall survival in the low-risk group. In multivariable models accounting for clinicopathologic differences the dose of adjuvant RT was not associated with mortality. On Cox proportional hazard modeling, adjuvant RT (HR 0.94; CI 0.43-2.08) or CRT (HR 0.96; CI 0.45-2.11) did not significantly improved survival compared with surgery alone in the intermediate-risk group (reference). Similar results were seen in the low-risk group. The composite number of pathologic risk features significantly improved risk stratification.ConclusionWe provide observational evidence that adjuvant RT or CRT does not provide a survival benefit for stage I HPV+ OPSCC with low- or intermediate-risk pathologic features.
| S-EPMC6533632 | biostudies-literature
Project description:BackgroundTreatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity.MethodsThis study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years' smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin).ResultsFifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6-75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6-59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0-42.7 months); one subject remains alive with disease.ConclusionThe results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1-2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC.Implications for practiceTransoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.
| S-EPMC8176976 | biostudies-literature
Project description:The population of survivors with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) is rising. The improved prognosis of this etiologic subset is reflected in new staging guidelines as well as ongoing deintensification trials aiming to preserve excellent survival while decreasing treatment-related toxicities. However, as staging criteria and treatment standards evolve in the era of transoral surgery and deintensification, little is known regarding the needs and treatment preferences of patients with HPV-OPSCC. Herein, the current knowledge regarding treatment preferences and priorities, quality of life and concerns among patients with HPV-OPSCC is reviewed.
| S-EPMC6275561 | biostudies-literature
Project description:Opinion statementThe rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.
| S-EPMC8178129 | biostudies-literature
Project description:PurposeTo report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.Materials and methodsMajor inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m2 once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events).ResultsOne hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events.ConclusionClinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.
| S-EPMC7010421 | biostudies-literature
Project description:Human papillomavirus-associated oropharynx cancer (HPVA-OPC) is rapidly increasing in incidence and has unique epidemiologic, molecular, and biologic characteristics. Despite being recognized as having superior prognosis, current evidence does not support less intense therapy compared with HPV-negative OPC. Current combined modality therapies confer a significant risk of morbidity, and patients with HPVA-OPC have a younger median age. These patients, therefore, live longer with the adverse effects of treatment, and this spurs the development of treatment deintensification trials that attempt to decrease treatment-related morbidity without compromising efficacy. Many radiation and chemotherapy de-escalation trials are underway. Minimally invasive surgical techniques are also being evaluated. It is important to identify the ideal patient group for treatment deintensification and to define prognostic risk groups to avoid undertreating the poorer-risk subset in HPVA-OPC, and validated biomarkers are needed to identify patients with the best prognosis. Significant smoking exposure mitigates the favorable prognosis of HPVA-OPC. Currently, less intense treatment is an option only in the setting of clinical trials, and patients with HPVA-OPC should be offered clinical trial options whenever they are available. Finally, recognition of novel therapeutic targets and signaling pathways is critical to the development of new treatment strategies that are desperately needed for patients with poor risk and those with recurrent and metastatic disease.
| S-EPMC5814107 | biostudies-literature
Project description:BACKGROUND:Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence of human papillomavirus-driven oropharyngeal cancer (HPV-OPC). METHODS:This study identified 161 incident oropharyngeal cancer (OPC) cases diagnosed at the University of Pittsburgh (2003-2013) with pretreatment serum. One hundred twelve had preexisting clinical HPV testing with p16 immunohistochemistry and HPV in situ hybridization (87 were dual-positive [HPV-OPC], and 25 were dual-negative [HPV-negative]); 62 had at least 1 posttreatment serum sample. Eighty-six of the 161 tumors were available for additional HPV16 DNA/RNA testing (45 were dual-positive [HPV16-OPC], and 19 were dual-negative [HPV16-negative). HPV16 E6 antibody testing was conducted with multiplex serology. The following were evaluated: 1) the sensitivity and specificity of HPV16 E6 serology for distinguishing HPV-OPC and HPV16-OPC from HPV-negative OPC, 2) HPV16 E6 antibody decay after treatment with linear models accommodating correlations in variance estimates, and 3) pre- and posttreatment HPV16 E6 levels and the risk of recurrence with Cox proportional hazards models. RESULTS:Seventy-eight of 87 HPV-OPCs were HPV16 E6-seropositive (sensitivity, 89.7%; 95% confidence interval [CI], 81.3%-95.2%), and 24 of 25 HPV-negative OPCs were HPV16 E6-seronegative (specificity, 96.0%; 95% CI, 79.6%-99.9%). Forty-two of 45 HPV16-OPCs were HPV16 E6-seropositive (sensitivity, 93.3%; 95% CI, 81.7%-98.6%), and 18 of 19 HPV16-negative OPCs were HPV16 E6-seronegative (specificity, 94.7%; 95% CI, 74.0%-99.9%). Posttreatment HPV16 E6 antibody levels did not decrease significantly from the baseline (P = .575; median follow-up, 307 days) and were not associated with the risk of recurrence. However, pretreatment HPV16 E6 seropositivity was associated with an 86% reduced risk of local/regional recurrence (hazard ratio, 0.14; 95% CI, 0.03-0.68; P = .015). CONCLUSIONS:HPV16 E6 antibodies may have potential clinical utility for the diagnosis and/or prognosis of HPV-OPC. Cancer 2017;123:4382-90. © 2017 American Cancer Society.
| S-EPMC5743332 | biostudies-literature
Project description:IntroductionLittle is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis.Materials and methodsThis is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression.ResultsAmong 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence.DiscussionTreatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling.
| S-EPMC6662631 | biostudies-literature
Project description:Oropharyngeal squamous cell carcinoma (OPSCC) originating from human papillomavirus infection has emerged as a new entity in head and neck cancer, defining a subset of patients with distinct carcinogenesis, risk factor profiles, and clinical presentation that show markedly improved survival than patients with classic OPSCC. De-escalation of therapy and identification of relevant biomarkers to aid in patient selection are actively being investigated. This review addresses the implications of these findings in clinical care.
| S-EPMC3740406 | biostudies-literature
Project description:BackgroundOropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.MethodsWe performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer.ResultsThe median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage.ConclusionsTumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)
| S-EPMC2943767 | biostudies-literature