Advances in Diagnosis and Multidisciplinary Management of Oropharyngeal Squamous Cell Carcinoma: State of the Art (original) (raw)
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Advances in the Management of HPV-Related Oropharyngeal Cancer
Journal of Oncology, 2019
Patients with human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than HPV-negative OPSCC when treated with standard high-dose cisplatin-based chemoradiotherapy. Consistent with this assertion and due to younger age at diagnosis, novel approaches to minimize treatment sequelae while preserving survival outcomes become of paramount importance. Here, we critically reviewed the evidence-based literature supporting the deintensification strategies in HPV-related OPSCC management, including radiotherapy dose and/or volume reduction, replacement of cisplatin radiosensitising chemotherapy, and the use of transoral surgery. Undoubtedly, further researches are needed before changing the standard of care in this setting of patients.
Cancers
Since there is no published randomized study comparing surgical and non-surgical therapeutic strategies in patients with oropharyngeal squamous cell carcinoma (OPSCC), the therapeutic management of these patients remains highly controversial. While human papillomavirus (HPV)-positive and HPV-negative OPSCC are now recognized as two distinct diseases with different epidemiological, biological, and clinical characteristics, the impact of HPV status on the management of OPSCC patients is still unclear. In this review, we analyze the current therapeutic options in patients with OPSCC, highlighting the most recent advances in surgical and non-surgical therapies, and we discuss the impact of HPV status on the therapeutic strategy.
International Journal of Cancer, 2014
Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High-risk human papillomavirus (HR-HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de-escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment deescalation in HPV-positive OPSCC.
Diagnosing HPV-Related Oropharyngeal Cancers: The Need to Speak a Common Language
Oral cavity squamous cell cancer (OSCC) and Oropharynx squamous cell carcinoma (OPSCC) are the most frequent forms of Head and Neck Cancers (HNCs) [1]. About 300,000 new cases of oral cancers are being counted yearly worldwide, having registered an increase of incidence of 225% in U.S.A. in the last 20 years, with about 50% of related deaths [2,3]. The relevant advances in treatments of OSCC during the last decades, allowed updated surgery techniques, robotic surgery, intensive induction chemotherapy and hyperfractionated radiotherapy to be currently applied to the advanced cases. Unfortunately, most of these therapies often carry severe acute and chronic side effects, heavily impacting on patients’ quality of life.
Journal of Clinical Oncology, 2017
Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPVassociated OPSCC for reduced radiation dose as a means of sparing late sequelae. Methods Patients with HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensitymodulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions. The primary end point was 2-year progression-free survival. Results Of the 90 patients enrolled, 80 were evaluable. Their median age was 57 years (range, 35 to 73 years), with the majority having stage T1-3N0-N2b OPSCC and a history of # 10 pack-years of cigarette smoking. Three cycles of IC were delivered to 77 of the 80 patients. Fifty-six patients (70%) achieved a primary-site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy. After median follow-up of 35.4 months, 2-year progression-free survival and overall survival rates were 80% and 94%, respectively, for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with , T4, , N2c, and # 10 pack-year smoking history who were treated with # 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with a radiation dose # 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or had impaired nutrition (10% v 44%; P = .025). Conclusion For IC responders, reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC. Radiation dose reduction resulted in significantly improved swallowing and nutritional status.
Oncotarget
Purpose: To investigate survival outcomes of patients treated with concurrent cetuximab and radiotherapy for primary management of both HPV positive and negative OPSCC, and compare the results to traditional platinum-based therapy. We hypothesize that the use of cetuximab in the HPV positive OPSCC patients will result in inferior survival based on tumor biological differences. Study design: A single institution retrospective analysis of 304 patients. The primary outcomes of interest were 1) overall survival and 2) relapse free survival. Pearson Chi-square tests were used to compare proportions between subgroups. One-way analysis of variance was used to compare the continuous variable age between subgroups. Kaplan-Meier method was used to produce survival curves, and comparisons between survival curves were made using the log-rank test. The survival functions comparing subgroups of chemotherapy were analyzed using semiparametric (i.e. Cox proportional hazards models) and fully parametric regression with Weibull distributions. Multivariable models were adjusted for age at diagnosis, gender, race, chemotherapy, radiotherapy, and cancer stage. Results: In the multivariable analysis, the hazard ratio for cetuximab compared to cisplatin or carboplatin/paclitaxel was HR=0.77[95% CI = 0.67, 0.90] in the HPV-group, suggesting more favorable outcomes for the patients on cetuximab in this group. However, in the HPV + cohort, the hazard ratio was 1.88 [95% CI = 1.42, 2.50] for those patients treated with cetuximab vs platinum-based therapy. Conclusions: Our data suggest that cetuximab may have inferior outcomes in HPV-associated OPSCC compared to traditional platinum-based therapy.
Annals of Oncology, 2018
Background: Patients with HPVþ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatmentrelated toxicity while preserving efficacy. Patients and methods: Patients were classified as low-risk (T3, N2B, 10 pack-year history) or high-risk (T4 or N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with 50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with 50% response received 45 Gy CRT (CRT45). Patients with lesser response received standardof-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results: Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3þ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P ¼ 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions: Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPVþ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration: Clinical trials.gov identifier: NCT02258659.
Journal of Cancer Research and Clinical Oncology, 2019
Objective To evaluate treatment outcomes after definitive chemoradiotherapy (CRT) for human papilloma virus (HPV)negative oropharyngeal squamous cell carcinoma (OPSCC). Materials and methods We analyzed data concerning HPV-negative OPSCC patients treated with curative intent. All patients received concomitant high-dose cisplatin-based chemotherapy. Two different RT techniques were used: (1) sequential boost IMRT (S-IMRT) to a total dose of 70 Gy (2 Gy/fraction); (2) simultaneously integrated boost (SIB-IMRT) to a total dose of 67.5 Gy (2.25 Gy/fraction). Survival outcomes were estimated. Results In total, 69 HPV-negative OPSCC patients were included (n = 40 S-IMRT; n = 29 SIB-IMRT). The median follow-up time was 40 months. The 3-year overall survival, disease-free survival, distant metastasis-free survival and locoregionalfree survival were 67.1%, 63.3%, 64.5% and 66.0%, respectively. Alcohol abuse and advanced stage disease at presentation were the main risk factors for worse survival outcomes. Complete clinical response (cCR) at 3 months after CRT improved overall survival (86.3% versus 42.5%, p < 0.01). The cCR events were greater but not statistically significant in SIB-IMRT group compared to S-IMRT patients (69% versus 47.5%, p = 0.09). Conclusions The positive impact of cCR at 3 months on survival needs to be confirmed in randomized clinical trials, as well as its close correlation with SIB-IMRT technique. A proper stratification of HPV-negative OPSCC patients should be paramount to tailor treatment strategy in the near future.
European Archives of Oto-Rhino-Laryngology, 2016
We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV? OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year diseasespecific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV?. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV? patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV? OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.