Chapters

Radiation dose #25

There’s not a lot to add. I’ve updated the body changes post with new information regarding weight, swallowing, and mucositis.

It’s nice that, really, I don’t feel sick. I’ve no fatigue or nausea. With the assistance of 6 x 500 mg Tylenol per day, benzydamine, and magic mouthwash, I can still swallow without significant difficulty. I get a dry mouth when doing any kind of exercise, but having a water bottle handy keeps that in check. I don’t have any significant saliva issues.

The biggest on-going problem is the change-of-taste one. Nicely, oatmeal seems to taste fine again. I’m going to test eating bread today, because last night I had a couple bites of a hamburger sandwich and the bun didn’t taste bad, and some breads are really high in calories.

Carbonated water (via a Sodastream) is a god-send. It cleans bad tastes, and stinging sensations on the back of my mouth, right out. If I sip a bit just before swallowing some food, it also keeps at bay the stinging sensation that some foods generate.

We’re coming into a long weekend, so no radiation for the next three days. And then, for reasons unknown to me, my double-dose will happen Thursday next week instead of Tuesday. It might be irrational, but I’m glad of these “reprieves”. Even though I don’t feel as if I’m doing as poorly as I might, I feel as if I’ll feel “good” longer if I have fewer doses now. But, as my radiation oncologist said, “the first four weeks for you have been easy-peasy; the next will be much harder”. I guess there’s no avoiding it.

But, bring on the weekend!

Radiation dose #18

It’s August 22, 2019 and, not unexpectedly, things aren’t getting any better.

At this point, nothing tastes good, and most things taste bad. My wife is being very supportive in trying to find foods, or ways of preparing foods, that aren’t distasteful, but it’s really hard. It appears that bread, and anything with bread in it, tastes bad/metallic. Many fruits (notably strawberries, bananas, plums, peaches) have juice that starts a burn in the back of my throat. I’ve read that some people find using plastic cutlery reduces the metallic tastes they experience, so I’m going to start testing that to see if it works for me. Also, carbonated water (thanks to friends for lending us their Sodastream) clears the bad taste from my mouth really quickly.

Mucositis does not appear to be a big problem for me yet. My gums are rough, but not sore, and I don’t have any ulcers on them, my tongue, or my cheeks. My soft palate and throat are sore, but not in a way that bothers me when I’m just sitting around.

It’s when I swallow that I have pain in my throat. Given that the centre of pain seems to be in a different place each day (e.g. right side, left side, higher, lower), I have the feeling that it’s a muscular thing rather than surface thing. It feels as if muscle tissue is being damaged and then regenerated, and the new muscle isn’t happy being stretched. Repeated stretching/swallowing reduces the pain. As does the use of 2 Tylenol 500 mg 4 times a day.

I wake up with a very dry mouth, and during the day my mouth dries out quickly, so I am drinking more water. But I haven’t had the “ropey” saliva that some people report.

I have to say that, when I’m busy doing things I enjoy I don’t really notice problems. The real problems come when eating, so eating is no longer enjoyable (and mostly off-putting) so I’m losing weight more days than not. I’ll probably deal with that by downing more high-protein, high-calorie drinks, and eating more ice cream; milk doesn’t taste bad.

I’ve updated my Body Changes page.

Radiation dose #12

Today is Friday August 16, 2019, and I’ve had 12/35 doses of radiation. I’m at 187.2 lbs, so I’m maintaining my weight.

So far, things have gone fairly well, I think. I was warned that the day after my double-dose day (Tuesdays) I would probably feel more fatigued, but I haven’t felt any fatigue at all on any day. I’m guessing that’s due in part to the fact that I’m not on chemo.

I’m also too busy to be fatigued. My son is visiting from the UK for 10 days, and he, my wife, and I have been replacing a portion of fence in our backyard. That’s involved grubbing out concrete that held the old posts, fetching cement and road base, installing sonotubes, setting upright the new 10′ long posts, mixing concrete in a wheelbarrow, and pouring it. Because I’m kinda picky about things, I’ve been doing the majority of the sweat labour, with my son getting to do the really heavy grunt work of lifting the largest chunk of concrete out of the ground. That, and lots of dog walks, keeps me active.

I’ve noticed a couple of changes.

  1. It’s becoming harder to swallow; not so much in a pain way as a mechanical way. I first noticed it a couple of days ago (after dose 10) when doing my swallow exercises. The Mendelsohn exercise, where you swallow and “freeze” your Adam’s apple at its highest position, became a little more difficult to do the first 2 or 3 times of a set of 10. Then, when doing the jaw stretch where I open my mouth as wide as possible, I noticed some small, sharp pain in the muscle behind where my soft palate joins with my right cheek.
    Today my swallow function is definitely more difficult, though not much and not painfully. The jaw stretch is noticeably painful, and it’s becoming more difficult to “pull” my tongue to the right when doing tongue stretches.
  2. And I also noticed after dose 10 that my gums, more so on the right side of my mouth, were feeling “rough”. Today, after 12 doses, it feels like the inside of my lower lip is also a little rough. I wonder if these are early signs of mucositis.

I’ve been taking benzydamine hydrochloride (aka Tantum, Difflam) as a prophylactic measure against mucositis. I found that it’s WAY cheaper to buy it at Costco than at my local pharmacy. My radiation oncologist has now issued me a prescription for magic mouthwash. At the Victoria Cancer Clinic, this version of the mouthwash contains diphenhydramine liquid, hydrocortisone injection, nystatin suspension, and distilled water. Because I need to have this filled by a compounding pharmacy, I’ll have to call around to see who offers the best price.

So, no real complaints. I am so lucky that the clinic is just a 5 minute bike ride from my home. Oral care takes a bit of work, but I’m happy to do it if I can reduce the mucositis symptoms. I think I’ve said it before, though; eating enough to keep my weight at 20-lbs-over-normal is a chore. By nature, I’m just always full, so finding the desire to eat is tough. My wife’s doing a great job of trying to find interesting and calorie-rich foods that don’t fill me up too much, so thankfully I’m no longer eating mounds of spaghetti. A&W Teenburgers taste REALLY good, and are worth 500 calories, so that’s fun!

One dose left this week, then a couple of days off to see how things consolidate.

Radiation dose #6

Well, things have been going pretty well so far. I’m on a 6 doses per week, 6 week schedule, getting two doses on Tuesdays 6 hours apart. Yesterday (Thursday August 8, 2019) was my 6th dose. This morning I awoke with what I expect is the beginning of dry mouth. Not so bad so far.

Really, the two biggest problems I’ve had so far are unrelated to the radiation.

  1. I’ve put on 20 lbs of weight, and pounding back the food has been a truly unpleasant chore. In order to not feel unpleasantly full at the end of the day, and needing to eat over 4000 calories a day to gain the weight I wanted, I’ve been eating about 2000 calories for breakfast and then cutting down to 1000 for lunch and dinner. Years ago I weighed over 200 lbs, but I’ve been closer to 165 for the past 3 years since I retired; eating 2000 calories for breakfast has been just no fun. But I hit my target weight, and I’ve cut back to a 2800 calorie maintenance diet, so now I feel much better. I’m just hoping 2800 will keep me in the 185-190 lb range.
  2. I have neck-muscle related headaches. These result (I think) from a) the Shaker exercise my speech language pathologist has recommended, b) upper-body weight training exercises, and c) stress. I could really use a good massage a couple of times a day; I’ll have to talk to my personal support team here at home about that . I think I’ll start popping an ibuprofen in the morning, and I need to look into methods for relaxing my muscles; I hear Jon Kabat-Zinn is the author to read.
  3. My dietitian is really happy with the way I’ve put on 20 lbs while focusing on building muscle mass and ensuring good nutrition. The app “My Fitness Pal” has been REALLY helpful in monitoring my daily intake.

The General Practitioner in Oncology assigned to me at the Victoria Cancer Clinic prescribed benzydamine hydrochloride (aka Tantum, Difflam) to be used prophylactically to reduce the symptoms of mucositis. Unlike products like Caphosol and Gelclair that coat your mucosa, benzydamine is an analgesic that, if started soon enough, is supposed to delay the onset and severity of mucositis symptoms. I have my fingers crossed.

Body changes over time

This page will identify changes over time to physical attributes like my weight.

Weight Changes

  • Jul 29, 2019: As stated in other posts, I’ve been trying to bulk up prior to commencing treatments. That’s been fairly successful. It’s weird, though, to see how much my weight varies. I’m sure the variability reflects the time of day at which I took my weight, how much I’ve eaten prior to weighing, and how much water I’ve sweated off through outdoor activities.
  • Aug 23, 2019: Bulking up is over. Now I’m just trying to keep my weight up.
  • Aug 31, 2019: As you can see, my weight’s bouncing around like crazy. Part of the reason is that some days I weigh when I’m wearing my jeans, and some days I’m wearing lighter-weight shorts.
  • Sep 9, 2019:Weight continues to fall. Food tastes bad, cancer suppresses appetite, while tissue is being re-generated. But, I’m still above my normal weight, and I’ve only 4 doses left, so I’m hopeful this weight loss trend won’t last long.
May 22, 2019: Diagnosis Day
August 1, 2019: First Radiation Treatment
September 13, 2019: Last Radiation Treatment

Other Changes

Considerations for radiation therapy dosage and fractionation

Today (July 15, 2019) I added a couple of updates to Considerations regarding chemoradiation therapy (CRT).

I’ve also been looking into my radiation therapy (RT) options, assuming that I don’t go ahead with CRT.

Update June 22, 2019
I’ve decided to decline CRT (see here for details), and to go with the Victoria Cancer Clinic’s “standard” accelerated RT.

Terms

Conventional fractionation refers to giving the total radiation dose of 70 Gy as 2 Gy per dose, 1 dose per day, 5 days per week, for 7 weeks.

CERT-AF: Chemotherapy-Enhanced Radiation Therapy-Altered Fractionation

CERT-CF: Chemotherapy-Enhanced Radiation Therapy-Conventional Fractionation

Late morbidity, any chronic (i.e. long-term) or late-occurring health condition, whether or not it is a recognized late effect of the disease or treatment

Hyperfractionation, reducing the dose per fraction to reduce late morbidity; the total dose is then elevated in an attempt to improve local tumor control with equal morbidity, e.g. giving a total dose of 79.2 Gy as 1.2 Gy per dose, 2 doses per day at least 6 hours apart, 5 days per week, for 6.5 weeks.

Accelerated fractionation, reducing the overall treatment time to overcome cancer cell repopulation during a protracted course of radiotherapy, e.g. giving a total dose of 72 Gy as 1.8 Gy per dose, 1 dose per day except Fridays when a 2nd 1.5 Gy dose is given at least 6 hours later, 5 days a week for 6 weeks.

Hyperfractionation and accelerated fractionation schedules may reduce the risk of cancer coming back in or near the place it started (called local recurrence) and might help some people live longer. The drawback is that treatments given on these schedules also tend to have more severe side effects.

Radiation Therapy for Oral Cavity and Oropharyngeal Cancer March 2018

Radiation strategies

According to The Oncologist, February 1999, there are four major strategies for accelerating radiotherapy:

  • Pure acceleration using a dose per fraction of 1.8 Gy to 2 Gy, treating once per day on six to seven days of the week, and then using more than one treatment on one day of the week.
  • Acceleration using a split-course treatment, with low, frequent daily doses, followed by some time off, followed boost doses (it wasn’t clear to me what the schedule was for the boosts).
    In the paper, no accelerated split-course treatments had satisfactory survivability rates, and they had increased morbidity, some much after treatment. “… even with a reduced dose per fraction, a total dose of 70 Gy cannot be achieved in five weeks without unacceptable morbidity.”
  • The concomitant boost.
  • Accelerated hyperfractionated radiotherapy.

Options

Because I’m likely to decline the chemotherapy, I need to look at my radiation schedule options. My radiation oncologist has recommended a couple of possibilities, and has suggested that I research other recommendations. Here’s what I’ve learned so far.

Standard of care: treatment is concurrent high-dose chemoradiation therapy where the radiation component is a dose of 70 Gy over 7 weeks delivered once-daily (i.e. conventional fractionation) to gross primary and nodal disease in patients with AJCC Edition 7 stage III-IV OPSCC.

Accelerated 6×6 option: 70 Gy max in primary site, 6 weeks, 5 doses/week except for Friday which would have 2 doses (i.e. 6 doses per week)

Start heavy, then back off option: Start with the Accelerated 6×6 option, but if things are looking rough for me, then go back to the standard 5×7 schedule with no doubling up on Fridays.

Start light, then get tougher option: Start with the standard 5×7 option, and if I’m doing well with side effects, then ratchet up to the Accelerated 6×6 option.

Considerations

This ASTRO article recommends, “Altered fractionation also should be used for patients with T3 N0-1 disease not receiving concurrent chemoradiation.”

The following article indicates that accelerated options are not as good as hyperfractionation when compensating for lack of CRT.

Concomitant CRT and hyperfractionated RT are comparable to one another on indirect comparison in the radiotherapeutic management of locoregionally advanced HNSCC. Any form of acceleration (with or without total dose reduction) may not compensate fully for lack of chemotherapy

Concomitant chemoradiotherapy versus altered fractionation radiotherapy in the radiotherapeutic management of locoregionally advanced head and neck squamous cell carcinoma: An adjusted indirect comparison meta-analysis May 2015

The quotes below are from an ASTRO article that compares a variety of treatment options for OPSCC.

Either accelerated RT or hyperfractionated RT may be used in patients with OPSCC treated with altered fractionation definitive RT after a careful discussion of patient preferences and the limited evidence supporting 1 regimen over the other.
…
Altered fractionation should be used in patients with T3 N0-1 OPSCC treated with definitive RT who do not receive concurrent systemic therapy.

Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline July-August 2017

Chemotherapy decision

The following are questions that I put to my medical oncologist in a July 22, 2019 telephone conversation. His answers, in combination with the information I’ve picked up from other sources (see here for detail) have helped me make a decision; I’ll take accelerated radiation therapy (RT) instead of Cisplatin chemoradiation therapy (CRT).

Questions & Answers

Q:
It appears to me that the following are the most significant side effects of Cisplatin.  How avoidable or reversible are each of these?

A:
First, none of these effects can be avoided with the use of drugs.

  • ototoxicity and audiogram abnormalities
    Some damage to hearing function is likely, although it’s impossible to know whether the effects would be noticeable. A problem is that there is no one scale of “hearing impairment” that studies can rate their results against. The BC Cancer Agency’s monogram on Cisplatin reports the lowest likelihood of impairment, that being 31%, but my oncologist has seen studies that show impairment in 50% of patients. The question is: how impaired is impaired? Is it bad enough to make a significant difference to the patient?
    Interestingly:
    • using a low-dose, weekly Cisplatin treatment, rather than high-dose, tends to reduce ototoxic effects
    • although audio-metric tests are usually done prior to commencing Cisplatin treatment, the existence of those tests has not been shown to improve our ability to reduce the ototoxic effects
  • neuropathy
    Some damage is very possible, though not likely. The effects are not reversible.
  • renal dysfunction
    Unlike the body’s nervous system (e.g. nerves needed for hearing and touch), the body’s kidneys are very good at fixing themselves. The body will regenerate damaged kidney tubules, but has a very hard time regenerating damaged nerves. Damage done by Cisplatin to the renal system is reversible.
  • myelosuppression
    Damage to bone marrow is infrequent, and the body typically regenerates the damaged marrow quite readily.

Q:
I understand that, along with neuropathy may come a sensation called “Lhermitte’s sign”. The descriptions of this sensation remind me of an undiagnosed condition that I have.  I sometimes (roughly once a week?) experience an “electric shock” running from my neck, along my shoulder, and part way down my arm (usually my right).  This happens most notably when I’m eating, and almost only when I’m sitting.  It’s startling, but not debilitating.  I’ve always ascribed it to a “pinched nerve”.  Can you hazard a guess as to whether or not this might be exacerbated by Cisplatin?

A:
What I experience, and what my medical oncologist also experiences, is not Lhermitte’s sign. That condition is, typically, related to meningitis. What I have probably is indeed a pinched nerve, and will not be exacerbated by Cisplatin.

Q:
How likely is Cisplatin to give me “chemo brain”?

A:
Not likely at all. Chemo brain is a very real thing that is typically associated with breast cancer patients and the drugs that they use. Cisplatin does not easily cross the blood-brain barrier, and my oncologist has not seen evidence of Cisplatin-caused chemo brain in his head & neck patients.

Q:
Two trials comparing Cisplatin CRT to Cetuximab CRT (RTOG 1016 and de-ESCALaTE) have shown that Cetuximab and Cisplatin have similar toxicities, but that Cisplatin CRT has better survival outcomes than Cetuximab CRT

  • RTOG:
    • 5 yr OS 84.6% vs 77.9% (+6.7%)
    • 5 yr PFS 78.4% vs 67.3%  (+12.1%)
  • de-ESCALaTE:
    • 2 yr OS 97.5% vs 89.4% (+8.1%)
    • 2 year recurrence 6% vs 16.1% (-9.9%)

When we last talked, you said there really are no trials that have yet definitively shown that Cisplatin CRT is better than RT alone in treating HPV-positive oropharyngeal cancer.  Could/should one infer that the RTOG 1016 and de-ESCALaTE trial results imply similar, and possibly greater, differences in survival outcomes from Cisplatin CRT vs RT alone? 

A:
My oncologist believes that the survival rates of patients treated with Cisplatin CRT are better than those of patients treated with RT only. How much better is the question. Cetuximab is not a nice drug; it’s multiplier effect on RT side effects is greater than that of Cisplatin’s. It really is a drug of last resort, to be used with ECOG 0/1 patients who suffer from problems (hearing, neurological, renal) that would preclude Cisplatin.

Q:
You said before that, if it was you, you would have high-dose Cisplatin treatment.  When you say that, are you focused on survival and non-recurrence, or on overall QoL?

A:
Survival. But he already thinks long and hard about whether he would be making the right decision given how much is not known about the long-term effects of Cisplatin, and given that that the benefits of doing Cisplatin instead of accelerated RT are unknown.

Q:
Am I correct in believing that, regardless of whether one has infrequent high-dose or more-frequent low-dose Cisplatin CRT, the chances that I would suffer from some kind of long-term side effects (e.g. ototoxicity, peripheral neuropathy, renal dysfunction, “chemo brain”) would exceed 10%?  I’m trying to get a feeling as to what QoL is likely to be for me if I do high-dose, and whether it would improve with low-dose weekly.

A:
My oncologist did not offer a percentage likelihood that I might suffer some of these side effects. However, he does think it’s likely that I would suffer some level of at least one of the effects, although the level might not be significantly noticeable. Having said that, he is very concerned that Cisplatin might result in long-term, significant side effects.
A low-dose weekly treatment is still not considered the “standard of care” for HNSCC. Studies have not yet shown a significant reduction in side effects for given satisfactory levels of survival compared to the high-dose treatment.

Q:
Does Cisplatin CRT increase the severity of radiation side effects, especially beyond the level that accelerated RT would create?

Yes. Cisplatin is a pretty tough drug to take.

Decision

I’m not going to do chemo. Instead, I’ll go with an accelerated plan for RT; 35 doses over 6 weeks. On one day of each week I’ll have 2 doses separated by at least 6 hours.

  • Although I’m concerned that the cancer might recur, I’m comforted by knowing that the likelihood is low. My locally advanced cancer is relatively contained, and careful VMAT RT target design along with the accelerated schedule should ensure that cancer cells do not have a chance to re-populate.
  • The ototoxic effects of Cisplatin bother me. My dad is 90 years old, and he’s alone in groups, because his hearing is so bad. I don’t want to trigger hearing loss that might worsen over time.
  • Ever since I was diagnosed and learned about PEGs and nasogastric feeding tubes (that some people use for many many months), I’ve said that one of my goals was to avoid have a tube. If, by cutting out Cisplatin, I can reduce the symptoms that make eating difficult, then I’ll be one step closer to meeting this goal.

Glossary

Bolus: In radiation therapy, bolus is a material which has properties equivalent to tissue when irradiated. It is widely used in practice to reduce or alter dosing for targeted radiation therapy.

Locally advanced: Locally advanced cancer is used to describe cancer that has grown outside the organ it started in but has not yet spread to distant parts of the body. So, T3 N1 MO is locally advanced.

Sequelae: A condition, typically chronic, which is the consequence of a previous disease or injury.

Xerostomia: Dry mouth resulting from reduced or absent saliva flow. Xerostomia is not a disease, but it may be a symptom of various medical conditions, a side effect of a radiation to the head and neck, or a side effect of a wide variety of medications.

Considerations regarding chemoradiation therapy (CRT)

Introduction

In an effort to determine whether I want to receive chemotherapy concurrent with radiation therapy, I am finding sources of information relevant to this question. The following are links to relevant studies/articles, or quotes from cited papers.

How can chemo be applied?

Update July 17, 2019
Chemo may be used in several different situations: (American Cancer Society)

  • Chemo (typically combined with radiation therapy) may be used instead of surgery as the main treatment for some cancers. (This is called chemoradiation.)
  • Chemo (combined with radiation therapy) may be given after surgery to try to kill any small deposits of cancer cells that may have been left behind. This is known as adjuvant chemotherapy.
  • Chemo (sometimes with radiation therapy) may be used to try to shrink some larger cancers before surgery. This is called neoadjuvant or induction chemotherapy. In some cases this makes it possible to use less radical surgery and remove less tissue. This can lead to fewer serious side effects from surgery.
  • Chemo (with or without radiation therapy) can be used to treat cancers that are too large or have spread too far to be removed by surgery. The goal is to slow the growth of the cancer for as long as possible and to help relieve any symptoms the cancer is causing.

History of treatment options

The following is an excellent editorial article from Annals of Translational Medicine. It provides a very clear description of chemo treatments for OPSCC.

Current Standard Treatment

The standard treatment for HPV-positive OPSCC, as of April 2019.

The standard of care for the definitive nonoperative management of cisplatin-eligible patients with advanced disease is concurrent chemoradiation with high-dose cisplatin given every 3 weeks. For patients undergoing initial surgical resection, adjuvant chemoradiation with concurrent high-dose cisplatin given every 3 weeks is recommended for patients with positive margins and/or extranodal tumor extension.

Deintensification of treatment of patients with p16+ oropharynx cancer should only be undertaken in a clinical trial.

Role of Treatment Deintensification in the Management of p16+ Oropharyngeal Cancer: ASCO Provisional Clinical Opinion April 2019

Problems with Cisplatin

Cisplatin CRT leads to higher toxicity and morbidity in short and long term, and possibly has higher non-cancer mortality.

Disturbingly, 10-year results of RTOG 91-11 demonstrated increased non-cancer mortality in the concomitant chemo-radiation arm (30.8%) when compared to the induction chemotherapy arm (20.8%) and the radiation-alone arm (16.9%), suggesting the current system of monitoring and grading late effects of treatment may be inadequate [49]. Worth noting, however, is that larynx cancer patients have higher baseline comorbidity and thus late cisplatin-related toxicity may not be mirrored in the more medically fit HPV-positive OPSCC patient population.

Treatment de-intensification strategies for head and neck cancer November 2016

Regarding long-term side effects…

Oropharyngeal cancer caused by Human Papillomavirus (HPV) infection … has a better prognosis than most other head and neck cancers. Patients cured of their disease often have to live for several decades with the side-effects of their treatment which can be permanent and have a major impact on quality of life.

Cardiff University Centre for Trials Research

The mainstay of treatment is combined chemoradiotherapy, and the prognosis for survival is good, but many patients will have long-term experience with the debilitating side effects of treatment.

Human papillomavirus–associated oropharyngeal cancer: review of current evidence and management 2019

Regarding high vs low Cisplatin dosage schedules. Note that this study did not differentiate HPV-positive from HPV-negative.

Given concurrently with conventional radiotherapy in locally advanced head and neck cancer, high-dose three-weekly cisplatin has often been replaced with weekly low-dose infusions to increase compliance and decrease toxicity. The present meta-analysis suggests that both approaches might be equal in efficacy, both in the definitive and postoperative settings, but differ in toxicity. However, some toxicity data can be influenced by unbalanced representation, and the conclusions are not based on adequately sized prospective randomized studies. Therefore, low-dose weekly cisplatin should not be used outside clinical trials but first prospectively studied in adequately sized phase III trials versus the high-dose three-weekly approach

The Oncologist May 2017

Chemo-brain really does exist

Top

Problems with Cetuximab

At least three trials are investigating the pros and cons of using Cetuximab rather than Cisplatin in combination with IMRT.

  • 5 years results: RTOG 1016: Cetuximab versus high-dose cisplatin concurrent with accelerated IMRT (70 Gy in 6 weeks)
  • 2 years results: De-ESCALaTE HPV: Cetuximab versus high-dose cisplatin concurrent with RT (70 Gy)
  • No results yet: TROG 12.01: Cetuximab versus weekly cisplatin concurrent with RT (70 Gy) once per week

However, Cetuximab appears not to have suitable overall survival outcomes.

For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. 

Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial November 2018

Results of our study show that, in the setting of low-risk oropharyngeal squamous cell carcinoma, the use of cetuximab bioradiotherapy instead of cisplatin-based chemoradiotherapy resulted in no overall benefit in terms of toxicity but showed significant detriment in tumour control. Our trial also highlights that the good survival outcomes of HPV-positive low-risk oropharyngeal squamous cell carcinoma are in part a function of the type of treatment received, and not merely a reflection of favourable intrinsic tumour biology. Therefore, cisplatin-based chemoradiotherapy should continue to be considered the standard of care in this setting.

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial November 2018

Cisplatin vs Cisplatin & 5-FU

In the following, Regimen A was Cisplatin CRT (IMRT) with 6 weekly cycles, and Regimen B was Cisplatin and 5-FU CRT in 2 weekly cycles.

Patients on regimen A were more likely than patients on regimen B to experience thrombocytopenia (odds ratio 2.41, 95% confidence interval 1.14–5.14, P = 0.02); 46% (22 of 48) of patients on regimen A experienced acute thrombocytopenia compared to 26% (21 of 81) of patients on regimen B (Table 2). However, the majority of thrombocytopenia experienced (90.0%) was less than grade 2 in severity and therefore not limiting (Table 3)

Comparison of Acute Toxicities in Two Primary Chemoradiation Regimens in the Treatment of Advanced Head and Neck Squamous Cell Carcinoma June 2012

De-escalated treatments have good results

The following study reports that de-escalation of both RT and CRT is very possible.

As of July 11, 2019, it appears that the survival rates for HPV-positive OPSCC patients receiving radiation only (i.e. no chemo) are very high, in fact much higher than for many other cancers.

Several studies have demonstrated that amongst HPV-positive patients some have an extremely low oncologic failure risk (especially non-smokers with less than T4 or N2c-N3 disease) [32], [36]. For these patients the addition of chemotherapy to radiotherapy does not seem to significantly increase overall survival benefit, suggesting that chemotherapy may be omitted completely. Chen et al. [37] have reported very good outcomes in a series of 19 HPV-positive OPSCCs treated exclusively by radiation, including 17 (74%) patients with stage III/IV and 18 (79%) non-smokers (<100 cigarettes in a lifetime). The 3-years overall survival and locoregional control rates for patients with stage III/IV disease were 81% and 88%, respectively. Among the 18 HPV-positive patients who were never-smokers, the 3-years rates of overall survival and locoregional control were 100% for both.

Treatment de-escalation for HPV-driven oropharyngeal cancer: Where do we stand? January 2018

Can chemotherapy be completely removed, leaving only IMRT treatment?

An alternative de-intensification approach is the omission of chemotherapy. The ongoing HN-002 trial (NCT02254278) is a large randomised phase II study of nearly 300 patients assessing two different de-escalation strategies. Eligible patients are those with HPV-associated T1–T3 tumours with N0–N2b nodal status and ≤ 10 pack-years smoking history, falling under the low-risk classification put forth by Ang et al. [15]. Patients are randomised to receive accelerated radiotherapy alone to 60 Gy given six fractions a week over 5 weeks versus 60 Gy using standard fractionation over 6 weeks with dose-reduced weekly cisplatin (40 mg/m2 weekly, total 240 mg/m [2]). Retrospective data suggest that the weekly chemotherapy schedule results in significantly reduced severity of mucositis compared to the traditional schedule of delivery every 3 weeks [54]. Notably, both arms represent a 10 Gy reduction in total radiotherapy dose. The primary end-point of the study is 2-year progression-free survival of at least 85% as well acceptable swallowing function based on the MD Anderson Dysphagia Inventory. This combination efficacy and toxicity end-point is novel, and demonstrates the emphasis of selecting therapies in which patients are likely to be cured, but also have minimal long-term morbidity.

Treatment de-intensification strategies for head and neck cancer November 2016

Studies of radiation therapy (RT) vs chemoradiation (CRT) therapy showed RT alone to have very good results.

RESULTS: In all, 23 patients with HPV-positive cancers were identified. With a median follow-up of 28 months (range, 6-85 months), the 3-year actuarial rates of overall survival, locoregional control, and distant metastasis-free survival were 83%, 90%, and 88%, respectively.

CONCLUSION: These findings attest to the exquisite radiosensitivity of HPV-positive head and neck cancer. The clinical outcomes observed from this selected series compare favorably with historical controls treated by more intensive chemoradiotherapy strategies.

Definitive radiation therapy without chemotherapy for human papillomavirus-positive head and neck cancer November 2013

Apparent improvements from CRT may be false.

In this study of real-world patients what appeared to be improvement in OS with the addition of concurrent chemotherapy to conventional radiotherapy was confounded by HPV status.

Did the addition of chemotherapy to conventional radiotherapy improve outcomes in treatment of oropharynx cancer in Ontario, Canada? A marker-treatment interaction study 2016

Current thoughts

As of July 11, 2019, I am leaning towards not having any chemotherapy, but I’m still in my information-gathering phase.

I will be meeting with my radiation oncologist tomorrow to get answers to some questions, and I’ll try to get his opinion about this. I’ll also set up another meeting with my medical oncologist, and I’ll be attending an information session all about chemotherapy at the Victoria Cancer Clinic next Tuesday July 16 where nurses and pharmacists will be able to answer questions.

Updates, July 15, 2019

I found another article that indicates CRT is not recommended for Stage II (that’s me) HPV-positive oropharyngeal cancer.

Stage I-II: Concurrent systemic therapy is not recommended for patients with stage I-II OPSCC receiving definitive RT, due to a lack of evidence supporting its use for early-stage disease.

New ASTRO guideline establishes standard of care for curative treatment of oropharyngeal cancer with radiation therapy April 16, 2017

The American Cancer Society makes it clear that CRT is really tough.

Side effects tend to be worse if chemotherapy is given at the same time as radiation (chemoradiation). Both the radiation and the chemotherapy side effects are worse, which can make this treatment hard to tolerate. For this reason, it’s important that anyone getting chemoradiation be in relatively good health before starting treatment, that they understand the possibility of serious side effects, and that they’re treated at a medical center with a lot of experience with this approach.

Radiation Therapy for Oral Cavity and Oropharyngeal Cancer March 2018

Update, July 17, 2019

In the context of HPV-positive head & neck SCC, high-dose Cisplatin treatments significantly increase short-term side effects.

… higher incidences in severe (grade 3 or higher) adverse effects in functional mucosal, muscular fibrosis, as well as cytopenia and nausea/vomiting in the combined group … the addition of chemotherapy to radiotherapy increased the incidence of severe adverse effects (grade 3 and higher) from 34% to 77% …

Optimal regimen of cisplatin in squamous cell carcinoma of head and neck yet to be determined June 2018

Update, July 22, 2019

The following article lists the pros and cons of de-escalation, including the option of removing systemic therapy entirely in favour of using RT only.

Point/Counterpoint: Do We De-escalate Treatment of HPV-Associated Oropharynx Cancer Now? And How? May 2018 ASCO Educational Book

The following article indicates that smoking status is a very high determinate of recurrence, leading me to think that, because neither RTOG 1016 or De-ESCALaTE had results based on smoking status, that the chance of recurrence, under Cisplatin CRT, for me is lower than those studies indicate. These were, however, mostly Stage IV patients.

One hundred and two patients (82.3%) had HPV-positive tumors. Over two thirds (68%) of patients with HPV-positive tumors were tobacco users. Among HPV-positive patients, current tobacco users were at significantly higher risk of disease recurrence than never-tobacco users (hazard ratio, 5.2). Thirty-five percent of HPV-positive ever tobacco users recurred compared with only 6% of HPV-positive never users and 50% of HPV-negative patients. All HPV-negative patients were tobacco users and had significantly shorter times to recurrence, and had reduced disease-specific survival and overall survival compared with HPV-positive patients. Compared with HPV-positive never-tobacco users, those with a tobacco history showed a trend for reduced disease-specific survival but not overall survival.

Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence February 2010 PubMed

The following article indicates that for patients with low risk of metastasis, there was no significant difference in controlling distant metastasis between RT and CRT.

The [distant control] rates for HPV-positive, low-risk [of distant metastasis] N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT…

Deintensification Candidate Subgroups in Human Papillomavirus–Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis
February 2013 Journal of Clinical Oncology

The following article implies that some recurrences are due to inadequate volume delineation.

A significant proportion of local–regional recurrences from HPV-positive oropharyngeal cancer represented geographical misses which possibly could have been prevented with more meticulous attention to IMRT planning.

Inadequate target volume delineation and local–regional recurrence after intensity-modulated radiotherapy for human papillomavirus-positive oropharynx cancer June 2017 Radiotherapy and Oncology

Bulking up 2

I’ve got base of tongue cancer (T3 N1 MO).  I start treatment in a week and a half.  Expecting that I’m likely to lose 20-40 lbs, I’ve been trying to bulk up as much as possible, focusing on adding muscle mass, rather than fat, ‘cuz your body prefers to get energy from muscle when it’s undergoing chemoradiation.  To that end, I’ve started eating more (a lot more!) and exercising more (again, a lot more!).  I’m focusing on building up my big muscles (quads, glutes, lats), because that’s the easiest place to put on more muscle relatively quickly.  If I look misshapen, it doesn’t matter; in three weeks, when I start to lose my appetite, I won’t be going to the gym anymore, and my muscles will start to atrophy, hopefully back to where they started a month ago.  So, 13 km bike ride followed by an hour in the gym.  Exhausting, especially at age 64.

I went to https://www.calculators.org/health/weight-gain.php to figure out how many calories I’d need to eat to attain the weight I wanted in a given period of time.  Then, with My Fitness Pal (available on Google Play, or at https://www.myfitnesspal.com/), I’ve been able to see how many calories I’m eating for each meal, and how many more I need to eat to hit my target.  I’ve gotta say, I’ve never eaten so much in such a short time, and it’s not as fun as I’d like it to be.  But I REALLY don’t want a feeding tube, so I chow down.

Another benefit of My Fitness Pal is that it tells you how many nutrients you’re getting, including things like potassium, Vitamin C, sodium (yikes, there’s a lot in the things I eat!).  As I’m going along, I’m starting to make better choices about my calorie, fat, protein, and nutrient sources.  The bread we’ve been buying has an astonishing amount of sodium in it.  I’ve got a really good protein powder, but it too contains more salt than I’d like, given the quantity I’m eating.  My wife, though, has found a dry cottage cheese that’s high in protein and very low in sodium.