In an interview, Frakes discusses a recent study and the impact these data have on follow-up frequency and the overall treatment paradigm for patients with OPSCC.
The study examined data from 246 patients diagnosed with either HPV-positive or p16-positive OPSCC. Patients received definitive radiation therapy, with 85% of patients also receiving concurrent chemotherapy. Median follow-up was 36 months. All enrolled patients received a 3-month post-treatment PET/CT scan and physical examination every 3 months in the first year after treatment, every 4 months in the second year, every 6 months in years 3 to 5, and then annually.
In an interview withTargeted Oncology, Frakes discussed the findings from the study, as well as the impact these data have on follow-up frequency and the overall treatment paradigm for patients with OPSCC.
TARGETED ONCOLOGY:Can you tell us about your study in monitoring recurrences in HPV-positive oral pharynx cancer?
What we did is we looked at patients with HPV-positive oral pharynx cancer and wanted to determine how and when their recurrences were detected. We thought that was an important point to look at, especially with the rise of HPV-positive cancers being diagnosed, as well as the increase in survival and the decrease in toxicity. That could be a big problem and the question that needs to be answered is "how are we following our patients?"
If you look at the NCCN guidelines, it's just a one-size-fits-all. So whether you're HPV-associated or HPV-unassociated in your malignancy, the follow-up recommendations are still the same. So we looked at our patients, all 246 of them with either P16-positive oral pharynx cancer or HPV-positive oral pharynx cancer, and determined what the outcomes were. We looked at the local recurrences, and we found a 3-year local control rate of 97%. That's a great local control rate.
We also looked at how many failures there were and how they were detected. There were a total of 6 failures, and all 6 failures were noted by physical examination. Those examinations consisted of either direct visualization or laryngoscopy.
We next looked at our regional recurrences and we found, again, a 97% regional control rate. We found that the majority of those patients were detected by symptoms. So a patient would present with a neck mass or on their 3-month post-imaging scan.
I should say that our protocol at our institution is that all patients get a 3-month PET/CT scan post-treatment, and if that's negative then we just follow them clinically. We do see patients for a physical examination every 3 months for the first year, every 4 months for the second year, and then every 6 months between the third and fifth years. After that, we see them annually.
We did look at the regional recurrence risk and we found that most were either detected on either the PET/CT or based on the neck mass, or presenting symptoms. We found that the majority of these local and regional distant recurrences happen within the first 6 months post-treatment. That's when the follow-up is most important for these patients.
We also looked at the distant failure and found that the distant control rate was 91%, which is a very high control rate. Again, it was very similar to the regional control in that we found recurrences based on symptoms or the 3-month PET/CT scan.
We found that the first 6 months were the most important, and if the PET/CT scan was negative and the patient was asymptomatic, we didn't need to do any further imaging.
TARGETED ONCOLOGY:What would you say is the overall significance of the study?
Routine imaging isn't necessary. I think that's one major point and it brings out a lot for patients, whether that’s a decrease in stress and anxiety while waiting for a test result, or the financial burden on the patients for the costs of the tests and their time away from work. Within the next year there is estimated to be 30,000 patients with HPV-positive oral pharynx cancer, so if you're doing routine imagining then that's a huge burden for our healthcare system without any benefit to the patient.
TARGETED ONCOLOGY:Are there next steps to this study?
We hypothesized that reduced monitoring would decrease the anxiety, stress, and financial burden of patients, but we need more validation of that.
Some people may say that knowledge is power and that patients want to get that imaging and those test results to say they're clean. That's a great feeling, but I think that you can empower your patients by showing them the data that their scan is negative, they're cancer free, and they just need to be followed up by physical examinations. Some of the quality of life endpoints need to be teased out a little bit more, and to make sure that what we hypothesized actually translates to patient satisfaction.
TARGETED ONCOLOGY:Related to the HPV-positive cases, what are you noticing in the progression of treatment for these patients?
If you go further back, most of these HPV-positive oral pharynx cancer cases were smoking related. Patient outcomes were a lot poorer, patients had more toxicities from treatments, local failures, regional failures, and they had a lot more recurrences. Now we're really starting to see younger patients that are relatively healthy with HPV-associated malignancies that do well.
It's important in the future to make sure that we are not increasing toxicities. We have patients that are living a lot longer with no evidence of disease, so you want to make sure that their quality of life is still high. We did assess our toxicities in the study. We looked at what we considered meaningful toxicities, which were grade 3 or higher toxicities. These toxicities were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4, which is a valid grading scheme for toxicities.
What we found was after 3 months, it was 9% of our patients. At the time of their last follow-up, it was only 2% of the patients that had persistent late toxicities. This means that we are managing patients who had feeding tubes in place, making sure they're meeting with their speech and swallow coaches, making sure they're meeting with their nutritionists, and making sure that we're controlling their pains. This helps decrease the toxicities for our patients and I think that's where the future is going.
There is one major national study going on, on the deintensification of treatment, that goes into the theme of HPV-associated cancers and patients are doing well. We need to make sure that we are not compromising the quality of outcomes for the patients while still improving their quality of life and decreasing their late toxicities.
TARGETED ONCOLOGY:What are some of the late toxicities that are reported in these patients?
Specifically, in our series, tracheostomy was one. We had 2 patients that had a tracheostomy. One of the 2 was removed, and that could just be from the swelling of radiation that they needed that in place.
The most common one that we saw was the feeding tube. We don't prophylactically put feeding tubes into our patients unless they've had significant weight loss pretreatment and we think they would need one. Otherwise, we just do it on a case-by-case basis if they're not able to maintain their weight, not being able to swallow, and if they're meeting with their speech and swallow coaches and dietician and they're still losing significant weight.
We did have 6 patients that had ulceration, or soft tissue necrosis, of the skin on the jaw. Four of those 6 patients had successful treatment with hyperbaric oxygen. We are pretty aggressive in managing our late toxicities.