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.

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

Second meeting with radiation oncologist

At my request, my wife and I met my radiation oncologist (RO) at the Victoria Cancer Clinic on Friday July 12, 2019 to talk about the following.

  • From a prognosis perspective, am I Stage I or II?
  • What do you think of the idea of me not going with chemoradiation therapy (CRT), considering my preference for quality over quantity of life?
  • How would you change your current 5×7 radiation therapy (RT) planning if I don’t go with chemo?  Going with an accelerated, 6×6, schedule?  How would a change affect me?
  • What would the next course of action be if my 12-week PET scan has positive hits for cancer, and biopsies showed those to be true, not false-positives?  Can I have RT or CRT again?
  • How do I get it on record that agency doctors and staff may give my wife any information that they would give me, whenever she asks for that information?

Questions, and answers

Q: From a prognosis perspective, am I Stage I or II?

A: At T3 N1 M0, I’m Stage II using Edition 8 of the AJCC guidelines for HPV-positive oropharyngeal cancer (OPC).

Q: What do you think of the idea of me not going with chemoradiation therapy (CRT), considering my preference for quality over quantity of life?

A: Although the standard treatment for my situation is high-dose Cisplatin chemoradiation, and although I am an “ideal” candidate (because I’m early-stage and fairly fit), he completely understands my reluctance to take chemo. He says that:

  • the chemo might increase my overall survival rate 8% from roughly 85% to 93%, but that it might not increase it at all
  • chemo has a significant hit on quality of life, not just in the short term, but potentially in the long-term as well
  • RT is very effective on HPV-positive OPC

Q: How would you change your current 5×7 radiation therapy (RT) planning if I don’t go with chemo?  Going with an accelerated, 6×6, schedule?  How would a change affect me?

A: There are, actually, a number of “alternate” or “accelerated” schedules that could be used. These are just three.

  • Compared to 35 doses over 7 weeks (i.e. 5×7), giving 36 doses over 6 weeks (i.e. 6×6) improves local control of the tumor, and reduces the chance of it returning – but it also increases the side effects.
  • He suggests that we do 6×6 to start with, and if it looks like toxicity is a bigger problem than we’d like it to be, we could reduce to 5×7
  • Alternatively, we could start at 5×7, and if things look OK, increase to 6×6

Q: What would the next course of action be if my 12-week PET scan has positive hits for cancer, and biopsies showed those to be true, not false-positives?  Can I have RT or CRT again?

A: A few things would happen.

  1. If the PET scan showed any type of cancer other than OPC, then they’d treat that as new cancer.
  2. If the PET scan showed recurrences of the OPC, RT and CRT would not be options; surgery would be the only option.
  3. After the 1st PET scan, wait a bit and then do a 2nd PET scan to see if the 12-week one was just showing residual effects on tissue of radiation (e.g. scarring).
  4. If the 2nd PET still indicates possible cancer, do a biopsy.
    1. If the biopsy shows cancer, they do surgery to remove the lymph nodes.
      Note: cancer at the back of the throat doesn’t recur; it’s only in the lymph nodes that they might see recurrence.
    2. (Now, here’s where I think I might have misunderstood.) If the biopsy does not show cancer, they’ll still remove the nodes, because the biopsy might be wrong. (As I noted, I might not have gotten that right. But, at this phase of my treatment, I’m not going to worry about it. I’ll cross that bridge only if I reach it.)

Q: How do I get it on record that agency doctors and staff may give my wife any information that they would give me, whenever she asks for that information?

A: As far as my RO can tell from reading my profile, my wife can already get info simply by asking. There is a form available at the Health Records that I would need to complete so that staff at that office would comply with my wishes.

Next Steps

I need to search for more info about “alternative” and “accelerated” RT for HPV-positive OPC.

First meeting with Medical Oncologist

I met with my medical oncologist (MO) Thursday July 4, 2019 to talk about chemotherapy (aka systemic therapy).

Almost right off, my MO said that chemotherapy, for me, was entirely optional, which surprised me. I’ve always thought that the primary purpose of chemo was to implement a mechanism for killing off any cancer cells that might have migrated beyond the regions that surgery and radiation target.

But my MO corrected me; the primary purpose of chemotherapy, at least when applied to HPV related oropharyngeal cancer treatment, is to improve the efficacy of the radiation treatment. The platinum in Cisplatin (the drug that would be prescribed in my case) binds to the cancer cells and the platinum makes the cells more sensitive to the concurrent radiation therapy. Without the chemo, the radiation simply has a harder time killing the cells.

What I thought was the primary purpose of chemotherapy is instead the secondary purpose. And, what I also learned about HPV related base-of-tongue cancer, is that cancer cells very rarely migrate beyond the lymph nodes. Therefore, if the cancer is treated soon enough, as mine will be, that secondary “seek and destroy” purpose is almost unnecessary.

My MO also made me aware that, for HPV related oropharyngeal cancer, no randomized clinical tests have been conducted that show conclusively that the standard chemotherapy treatment actually has a significant impact on 5 year survivability. It’s possible that chemo would not actually help me.

A little background is required here. Please note that the following is what I remember my MO telling me; it may not be entirely accurate. I’ll provide updated information, and supporting citations, in future posts.

  • Older survivability studies of patients with oropharyngeal cancer showed 5 year survivability rates of roughly 60%. In those studies, patients who received chemotherapy in addition to radiation therapy had a survivability rate about 8% higher than those patients who had radiation therapy only.
  • But those studies did not differentiate patients who had smoking related cancer from those with HPV related.
  • Studies show that people who live 5 years after treatment for the HPV related version of oropharyngeal cancer do not die of the same cancer; they are cured.
  • Studies also show that the survivability rate for HPV related oropharyngeal cancer patients who receive both radiation and chemo therapies is around 80%
  • But no studies have returned results yet that show that the chemotherapy that HPV related patients receive has the same 8% impact on survivability. Given that the HPV related cancer is a very different beast from the smoking related version, it’s very possible that the impact of chemotherapy is much lower than 8%. In fact, it’s possible that the chemotherapy could have a negative impact on survivability rates, because chemotherapy comes with side effects that can be very devastating.
  • Nonetheless, the standard cancer treatment for oropharyngeal cancers, as recommended by ASCO (American Society Of Clinical Oncology) and ASTRO (American Society For Radiation Oncology), is radiation supplemented by Cisplatin chemotherapy. This will remain in effect until studies show that the chemotherapy is unnecessary. Studies have been started, but they have been running less than 5 years, so results aren’t in yet.

So I’ve got about 2 weeks to decide whether I want to have chemo. My MO is going to book a bed for me for the first day of treatment (see treatment plan below), and I can cancel it at the last minute (although giving a day’s notice would be better so they can give the bed to someone else).

Posts in the next couple of weeks will include my investigation into the pros and cons of chemo for HPV related oropharyngeal cancer. Those posts will include links to source materials.

Current Treatment Plan

  • Chemo-radiation therapy will start Monday July 29, 2019
  • I will be given radiation over a 7 week period. In that period I will have 35 daily treatments, Monday through Fridays.
  • I will have 3 cycles of chemotherapy. Each cycle will comprise 1 daily treatment. Treatments will occur on Day 1 and Day 22. If my MO thinks it’s appropriate, I will have a treatment on Day 43.
  • Cisplatin chemotherapy treatments take a long time, because it’s critical that the platinum be washed completely out of my vascular and renal system by the end of the treatment, and that my kidneys be checked before I leave the hospital. Therefore, just to make things a whole lot simpler, I will be checked in as an overnight patient for chemotherapy treatments.
  • I have the right to go through the first cycle, determine that the side effects are too uncomfortable to continue, and discontinue treatment. Similarly, my MO could also decide to terminate chemotherapy if he decides that costs of continuing do not warrant the hoped-for benefits.
  • My MO frequently suspends chemo treatments after the 2nd cycle

Alternative Treatment Plan

If I decline chemotherapy, my radiation oncologist would put me on an accelerated treatment plan. I would still receive my total dosages (70 Gy to the primary site and 56 Gy to elective sites), but over just 6 weeks. On one day of the week I would receive 2 doses instead of 1.

This alternative radiation plan is given to accommodate the lack of chemo. As I noted above, the primary purpose of chemo is to accelerate the death of cancer cells by making them more sensitive to concurrent radiation therapy. The doubling up of doses is intended to make up for the fact that the cancer will be less sensitive.

Other Systemic Therapies

The chemotherapy that my MO has in mind for me is known in BC as “HNLAPRT” (Head and Neck Locally Advanced Platinum Radiation Therapy). The BC Cancer Agency’s patient handout for this therapy talks about the following.

  • what Cisplatin is
  • its intended benefits
  • the HNLAPTR treatment summary
  • treatment protocol (i.e. cycle details)
  • chemotherapy side effects and management
  • radiation side effects and management

Other systemic therapies available for use with radiation therapy include the following. Patient handouts and protocol summaries for each of these can be found at the BC Cancer Agency’s Head & Neck Chemotherapy Protocols page.

  • HNLAALTPRT (Head and Neck Locally Advanced ALTernate Platinum Radiation Therapy)
    • The treatment cycle changes so that the patient receives smaller but more frequent doses
  • HNLACETRT (Head and Neck Locally Advanced CETuximab Radiation Therapy )
    • Cetuximab is used when Cisplatin cannot be used, for example when the patient’s renal function is already impaired, or already has tinnitus or some hearing loss
  • HNLACNFRT (Head and Neck Locally Advanced CArboplatin and Fluorouracil Radiation Therapy )
    • This treatment is very hard on the body and is very rarely used anymore

Cisplatin Side Effects

  • nausea, often with vomiting
    • The MO would attempt to reduce nausea by having me take anti-nausea medication prior to taking the Cisplatin. The anti-nausea drugs themselves have side effects.
  • diarrhea
  • mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract
  • damage to bone marrow leading to
    • reduction in number of red blood cells resulting in fatigue
    • reduction in number of white blood cells resulting in reduced ability to fight infection
    • reduction in number of platelets resulting in increased bruising
  • kidney damage resulting from platinum damage to cells
  • hearing loss
  • hair loss from the Cisplatin is rare
  • tinnitus is the perception of noise or ringing in the ears
  • neuropathy is the loss of feeling in fingers, hands, and feet, and can sometimes become permanent
  • weight loss that compromises health
  • increased susceptibility to auto-immune diseases

Why I am a good candidate for Cisplatin treatment

My ECOG performance status is 0. That means that I am “Fully active, able to carry on all pre-disease performance without restriction”. Therefore, I should be able to handle the additional burdens placed on my body by the chemo supplement better than someone at higher ECOG ratings.

The Eastern Cooperative Oncology Group (ECOG) is one of the largest clinical cancer research organizations in the United States and conducts clinical trials in all types of adult cancers.

The ECOG performance status is a scale used to assess how a patient’s disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis

Radiopaedia

Weight loss issues

My MO tells me that the dietitian that I’ve been assigned to is a person who is very determined to maintain my weight at acceptable levels, and will be on the MO’s case if my weight drops more than 10% of my baseline weight. From reading the HNLAPRT protocol document, I see that, when the 10% is hit, either the patient gets a feeding tube and the chemo dose drops by 25%, or chemo must be discontinued.

I asked which of my many weights is deemed the “baseline”, because, knowing that weight loss is an issue, I’ve been bulking up. I was 169 lbs when had my open biopsy on May 22, and my desire is to have that treated as my baseline; on my 6’1″ frame I’ll definitely be skinny if I drop to 152 lbs, but I won’t be on death’s door. According to my MO though, the standard baseline is defined as the weight I have when treatment commences, which I’m hoping will be around 185 lbs.

Thinking about this more, I’m starting to think I may be really wrong in thinking that allowing myself to drop 18% from 185 to 152 would be OK. That 10% figure indicates that the treatment is having a very significant effect on my body, and that the treatment needs to be amended some way to ameliorate the side effects.

My thoughts

I’m seriously considering not going with the chemo. I really want to minimize the side effects of my treatment, and some of the chemo side effects sound pretty severe.

I might also say, “Let’s try one cycle, and see how it goes.” But I don’t know how the radiation oncologist would like that; would he want, or not want, to accelerate his treatment?

I think I’ll chat this over with other members of “my” team (dietitian, radiation oncologist, speech language pathologist, and general practitioner in oncology) to get their thoughts.

First meeting with Radiation Oncologist

My wife and I met my Radiation Oncologist (RO) today (Friday June 28) for the first time.

He confirmed that his plan is for me to have 35 radiation sessions, 5 days a week for 7 weeks. Total dosage to the primary cancer site at the base of my tongue will be 70 Gy. Total dosage to the elective sites (sides of my neck) will be 56 Gy. They will use VMAT.

My next CT scan will be a week after I’ve had my teeth removed, to give my mouth time to recover and not skew the resulting images. The scanner will be tied to my RO’s planning software to allow him to design the doses.

Radiation treatment will commence about 10 working days after the CT scan. That makes it between Wednesday July 24 and Monday July 29. Those 10 days give my RO time to plan the targeting regime and for technologists to build my mask. It will also give my medical oncologist time to finalize chemotherapy plans (I meet with the medical oncologist Thursday July 4).

I told my RO that I’m not afraid of dying. As far as I’m concerned, death can’t be avoided, so there’s no point in worrying about it. But, although I’m not concerned about quantity of life, I am concerned about quality of life. So, we talked about my options regarding de-escalating dosages so that the side effects could be minimized.

We also talked about feeding tubes. I told my RO that I’d rather eat razor blades (a common way, I’ve heard, of describing the feeling of mucositis) than have a PEG. He told me that it’s common procedure in both the UK and in Toronto to insert PEGs early in treatment in anticipation of problems. In Victoria, though, PEGs aren’t inserted until it becomes obvious that they’re required. And, it sounds from him, that they’re having very good success not inserting PEGs. Fingers crossed.

My RO acknowledged that there are a variety of ideas about the appropriate intensities and volumes of radiation to give. His current thinking aligns with those of the BC Cancer Agency: although there are hopeful indications that de-escalation will be appropriate for HPV+ oropharyngeal cancers, randomized clinical trials have not yet shown that de-escalation will result in the same high survival rates that “standard” dosage plans have. Essentially, my RO said, it comes down to this:

  • I can have “standard” dosages, and go through a few absolutely miserable months of side effects, and feel very confident that I won’t ever have this cancer again, or
  • I can have “reduced” dosages, have reduced side effects, and take the chance that the cancer will come back and that I’ll have to go through this all over, or maybe worse if the cancer has spread.

During our discussion I commented that one of the earlier notes from my ENT indicated that my cancer was T2 N2a. My RO said that he didn’t necessarily agree with that; he thought that, although the lymph nodes were involved, I could be at N1; he wouldn’t be able to say more definitely though until he’d seen my PET scan (which happens tomorrow). The results of the scan should be ready in about a week.

My RO agreed with my expectation that the medical oncologist would recommend 2, possibly 3, chemo sessions. He pointed out that the low treatment frequency results from the fact that chemotherapy improves chances of survival by only 8% on average; without a doubt, radiation is the primary treatment for OPSCC.

And then he stuck the laryngoscope down my nose. Oh, how uncomfortable that is, even with Lidocaine sprayed in my nostrils. Unfortunately, he says that’ll be a very common occurrence for the next number of months.

He also manipulated my swollen lymph nodes. He was happy to say that they were still very mobile, which is a good thing. If they weren’t, that would indicate that the cancer in them had affixed itself to surrounding tissue, like the roots of a tree do in the soil. The less attached the nodes are, the less tissue there is to irradiate.

On our way out of the cancer clinic, my wife and I stopped off at the library in the clinic. It’s a very nice, soothing looking space, but it doesn’t have a lot of materials on head and neck cancers, and much of it is relatively old. I’ll continue to get my information from web searches and by double-checking via source citations.

The cancer clinic does host a Head & Neck Cancer Support Group. It meets one Tuesday of each month. I’ll attend at least one session to see what I can learn and what I can offer.

Possible Treatments

The following articles outline some of the treatments, along with treatment side effects, that can be proposed for a person with base-of-tongue cancer.

Treatments are one or more of surgery, radiation, chemotherapy.

Surgery

As of June 2019, my ENT is not recommending surgery.

Radiation Therapy

The BC Cancer Agency has prepared a tentative plan for me that includes radiation therapy. That plan indicates that the lymph nodes on the right side of my neck and the base of my tongue will be hit with 35 doses of radiation totalling 75 Gy (definition of Gray). Other areas, like my upper and lower right jaw, and the rest of my neck, might be hit with 56 Gy over the 35 doses.

BC Cancer Agency’s preliminary idea of where radiation will be, and approximate dosages. The Upper and Lower teeth are those discussed in this post.

Concerns

I’ve found pages that indicate radiation exposure could be much less than the “standard” 56 Gy currently planned for me. This is something I want to talk over with my radiation oncologist when we meet.

Methods

Intensity Modulated Radiotherapy (IMRT)

Intensity modulated radiotherapy (IMRT) is a type of conformal radiotherapy. Conformal radiotherapy shapes the radiation beams to closely fit the area of cancer. … This means that the tumour receives a very high dose and normal healthy cells nearby receive a much lower dose. … IMRT can be very helpful in areas such as the head and neck, for example to avoid the spinal cord or salivary glands.

https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/radiotherapy/external/types/intensity-modulated-radiotherapy-imrt

Volumetric Modulated Arc Therapy (VMAT)

VMAT is a type of IMRT technique. … VMAT is different to normal IMRT in that the radiotherapy machine rotates around the patient during a radiotherapy beam in an arc shape. The machine continuously reshapes and changes the intensity of the radiation beam as it moves around the body.  Giving the radiotherapy in this way makes it very accurate, shortens the treatment time, and uses a lower overall dose of radiation.

https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/radiotherapy/external/types/intensity-modulated-radiotherapy-imrt

I’m fortunate that VMAT is offered at the Victoria Cancer Clinic.

Systemic Therapy (aka Chemotherapy)

to be done