Efficacy Maintained, QoL Improved With Radiation Dose Reductions in Oropharyngeal Cancer

Barbara Ann Burtness, MD

Reducing radiation and chemotherapy dose in low-risk HPV-associated oropharyngeal squamous cell carcinoma may still prevent disease recurrence while improving quality of life, according to two separate sets of data presented at the 2015 ASCO Annual Meeting.

The first, a prospective multi-institutional phase II study, looked at 43 low-risk patients who had received the reduced dose of 60 Gy intensity modulated radiotherapy along with concurrent weekly intravenous cisplatin (30 mg/m2) for the treatment of HPV-associated oropharyngeal cancer.¹

The primary endpoint was pathological complete response (pCR) which was achieved by 86% (37/43) of patients. All 6 non-pCR cases were limited to microscopic foci of residual cancer. The median time to biopsy/neck dissection was 9 weeks (7-14 weeks). After a median follow-up of 15 months (4-31 months), all patients were alive with no evidence of disease.

The second study used the Vanderbilt Head and Neck Symptom Survey (Version 2.0) to investigate the impact of a reduction to 54 Gy radiation intensity on toxicity risk in patients with low-risk HPV-associated oropharyngeal cancer.² Eighty patients were enrolled in the study (3 did not receive radiation) with 44 patients classified as having no evidence of disease at 12 months posttreatment (35 received ≤54 Gy and 9 received >54 Gy).

Moderate to severe average symptom scores were reduced with the lower radiation dose, with 6% of patients in the reduced dose group experiencing mouth pain versus 25% in the higher dose group, and 27% versus 50% experiencing general pain, 6% versus 40% experiencing taste/smell changes, and 13% versus 25% experiencing vocal side effects in the lower dose and higher dose groups, respectively. The most dramatic impact was the ability to swallow solids, with 35% of those in the lower dose group reporting difficultly versus 100% in the higher dose group, reaching statistical significance (P = .01).

OncLive: You were involved in a phase II trial looking at the deintensification of chemotherapy and radiation for HPV-associated oropharyngeal cancer. What were the most significant findings from that trial?

To better understand how these studies could impact the treatment paradigm in HPV-associated oropharyngeal cancer, OncLive spoke with an author on both studies, Barbara Ann Burtness, MD, professor of Medicine (Medical Oncology), clinical research program leader, Head and Neck Cancers Program, co-director, Developmental Therapeutics Research Program, Yale Cancer Center.Dr Burtness: This trial was a multi-institutional phase II trial that looked at 43 patients who had low-risk HPV-associated oropharyngeal squamous cell carcinoma. The trial was designed so that everyone was treated with a less intense treatment than what has been historically used for these patients. Instead of receiving 70 Gy of radiation, they received 60 Gy of radiation. Instead of receiving high-dose cisplatin on an every-3-week schedule, they received 30 mg/m2 of cisplatin weekly.

At the conclusion of treatment, everyone underwent neck dissection to determine if they had experienced a pCR. That was seen in 86% of patients. The neck dissection can also be seen as part of the treatment. Therefore, if we look at the total group of 43 patients, with a median follow-up of 15 months, there was no incidence of recurrent disease.

What impact do you see this research having?

On the one hand, a trial that still uses cisplatin and incorporates a neck dissection may not be seen as a deintensified approach. However, I think data on 43 patients treated with 60 Gy who still have 100% disease control is significant. There has also been a lot of interest looking at weekly cisplatin versus high-dose cisplatin every 3 weeks, because it may be associated with a lower risk of hearing loss and renal injury. Therefore, these results will be very helpful going forward.

It is premature to think about treating patients with 60 Gy instead of 70 Gy, but I do expect that in 4 or 5 years there will be a new paradigm of treating low-risk patients with less intense radiation.

Another study you were involved in looked at the impact of dose deintensification on quality of life. What were the main goals of that study?

The question we wanted to answer was, “Is there any benefit of getting a reduced dose besides not having to come in for additional radiation?”

In this study, we aimed to identify a subset of patients with good prognosis HPV-associated oropharynx cancer who can be cured with a less aggressive chemoradiation approach than what has been standard, and to see how that impacted their quality of life. We found that patients indeed have a better quality of life with a reduced dose.

How was the trial designed?

Patients with HPV-associated locally advanced oropharynx cancer were treated with induction chemotherapy. If they had a clinical complete response to the chemotherapy at the primary tumor site, we then treated them with a reduction in the dose of radiation for the definitive treatment. Instead of getting 70 Gy of radiation, they got 54 Gy, which is a substantial reduction. They also received cetuximab instead of cisplatin.

What was the impact of the dose reduction on the patients’ quality of life?

The most difficult symptom for patients undergoing this treatment is difficulty swallowing solids. Using the Vanderbilt Head and Neck Symptom Survey, we determined that there was a reduction in that side effect from about 100% in the patients who received full-dose radiation, to 37% in the patients who received reduced radiation. Another difference we saw between the two groups was in general pain: 50% of patients experienced pain in the group that received full dose versus 27% in the group that had received reduced dose radiation.

We examined a number of other side effects that patients had and some, including difficulty swallowing liquids, were not that impacted by the change in dose. However, across the board when we clustered all the symptoms together, 100% of patients in the control group had aftereffects of treatment that lasted 12 to 24 months, while only 70% of patients in the reduced dose group did. Overall, we think this gives us a good understanding for further study of reduced dose research and provides us with some targets for good endpoints that we can use in future clinical trials.

References

1. Chera BS, Amdur RJ, Tepper JE, et al. A prospective phase II trail of de-intensified chemoradiotherapy for low-risk HPV-associated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2015;33 (suppl; abstr 6004).
2. Cmelak A, Li S, Marur S, et al. Symptom reduction from IMRT dose deintensification: Results from ECOG 1308 using the Vanderbilt Head and Neck Symptom Survey version 2 (VHNSS V2). J Clin Oncol. 2015;33 (suppl; abstr 6021).