A phase II study funded by the National Institutes of Health(NIH) shows that certain HPV-positive oropharyngeal cancer (HPV-POC) patients can safely receive a lower-dose radiation therapy. The therapy is using a new approach that customizes radiation dose based on response to induction chemotherapy and other prognostic factors. These findings showed that lowering the dose of radiation therapy did not compromise outcomes. In 95% of all cases patients were alive two years after starting treatment. The results of this study were presented at the 50th Annual Meeting of the American Association of Clinical Oncology(ASCO), being held May 30 – June 3, 2014, in Chicago, Ill.
HPV causes an epidemiologically and clinically distinct form of oropharyngeal squamous cell carcinoma. These HPV-positive OPSCCs have risk factors related to sexual behavior whereas HPV-negative cancers are strongly associated with tobacco and alcohol use.[1][2]
?Treatment for head and neck cancer can be quite grueling, so it?s very encouraging to see we can safely dial back treatment in patients with less aggressive disease and an overall good prognosis, particularly for young patients who have many years to deal with long-term side effects,? said lead study author Anthony Cmelak, MD, a professor of radiation oncology at the Vanderbilt-Ingram Cancer Center in Nashville, TN. ?However, we need longer follow-up, as well as confirmatory phase III data, before we can recommend applying this strategy in practice.?
…lowering the dose of radiation may be safe and effective for this group of patients if they respond well to induction chemotherapy…
Oropharyngeal cancers
It is estimated that approximately 70% of newly-diagnosed oropharyngeal cancers are related to human papillomavirus or HPV, and the incidence of HPV-related disease appears to be rising. [1] Patients with HPV-positive tumors tend to have a substantially better outcomes compared to patients with HPV-negative disease. [2]
Study
In this first-of-a-kind study, 90 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma received induction chemotherapy with paclitaxel (Taxol?; Bristol-Myers Squibb/BMS), cisplatin (Platinol?/Platinol?-AQ; Bristol-Myers Squibb/BMS) and cetuximab (Erbitux?; ImClone/Eli Lilly and Company/Bristol-Myers Squibb). Such therapy sensitizes the cancer to further treatment, and has been shown to decrease the risk of cancer spread, predict the tumor?s sensitivity to radiation, and relieve tumor-related side effects.
The 62 patients who had a complete clinical response to induction chemotherapy, meaning they had no signs of cancer on endoscopic exam, received a reduced dose (54 Gy) of intensity-modulated radiation therapy (IMRT), and the rest of the patients received standard dose IMRT (70 Gy). IMRT uses advanced technology to manipulate beams of radiation to conform to the shape of a tumor. All patients received standard cetuximab along with radiation.[3]
Primary endpoint
The study met its primary endpoint of progression-free survival. Among patients who received lower-dose IMRT, the two-year overall and progression-free survival were 93% and 80%, respectively; survival was slightly higher among patients with less than 10 pack-years of smoking and earlier-stage disease (two-year progression-free and overall survival were 92% and 97%, respectively). As expected, outcomes were worse for the higher-risk patients treated with the standard IMRT dose (two-year overall survival and progression free survival were 87% and 65%, respectively). According to Cmelak, lower-dose IMRT would not be suitable for patients with HPV-negative disease or larger tumors.[3]
Reducing IMRT dose offers patients a better quality of life by decreasing the risk of debilitating, often long-term, side effects ? trouble swallowing, dry mouth, loss of taste, neck stiffness, and thyroid problems.
Patients will be followed on this study for five years to capture late recurrences. Researchers are also planning another randomized phase II study that will explore an even less intensive approach involving so-called reduced-field IMRT to treat only areas of initial gross tumor in patients with low-risk HPV tumors. It is hoped that this approach would yield similar survival benefits with further reductions in the risk for long-term side effects.
Safe and Effective
?We?ve known for some time that patients with HPV-positive oropharyngeal cancer have a better prognosis than those with non-HPV tumors. This study shows that lowering the dose of radiation may be safe and effective for this group of patients if they respond well to induction chemotherapy,? noted Gregory A. Masters, MD, ASCO Expert. ?Understanding the biology of cancer allows us to offer more precise therapies for individual patients, and this research offers one more way to provide effective treatment with less toxicity, improving patients? quality of life.?
For more information:
[1] D’Souza G, Gross ND, Pai SI, Haddad R, Anderson KS, Rajan S, Gerber J, Gillison ML, Posner MR. Oral Human Papillomavirus (HPV) Infection in HPV-Positive Patients With Oropharyngeal Cancer and Their Partners. J Clin Oncol. 2014 Apr 28.[Article][PubMed]
[2]Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301.[Article][PubMed]
[3] Cmelak A, Li S, Marur S, Zhao W, Westra WH, Chung CH, Gillison ML, Gilbert J, Bauman JE, et al. E1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC). 2014 ASCO Annual Meeting. Oral Abstract Session. Monday June 2, 8:00 AM to 11:00 AM. Abstract No: LBA6006/ Citation: J Clin Oncol 32:5s, 2014 (suppl; abstr LBA6006)[Abstract]
Photo: Anthony Cmelak, MD speaks during the Improving Patient Care and Quality of Life Press Conference at the American Society of Clinical Oncology Annual Meeting (ASCO). Photo Courtesy: ?ASCO/Scott Morgan.
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