Chronic pain in survivors of childhood cancer

Chronic pain in survivors of childhood cancer: a developmental model of pain across the cancer trajectory: PAIN – Oct 2018

When I took notes on it, this article was fully available, but now as I’m blogging it, it’s no longer available. Unfortunately, I’ve lost access to the tables and figures of the full text.

1. Introduction

Over the past 50 years, advances in treatment have resulted in significant improvements in pediatric cancer survival rates. Such improvements have been due, in part, to more aggressive treatment protocols, which in addition to the disease itself and the psychosocial impact of the disease, place survivors at risk of developing an array of late effects, including  

• neurocognitive impairment chronic health conditions,
• fatigue and poor sleep,
• social impairment, and
• psychological distress.

I notice this is the exact list given for the “late effects” of chronic pain.   

Despite elevated and clinically significant pain being common among youth during and after cancer treatment, and evidence suggesting that pain persists into adulthood, pain has remained understudied relative to other late effects

Although we agree with this stance, we also see the need to take a step beyond to consider what is known about pain in pediatric cancer survivors, including adolescent, young adult, and adult survivors.

In this topical review, we aim to

(1) nonsystematically review the current empirical literature on pain in survivors of childhood cancer, highlighting gaps and limitations;

(2) draw from the extant literature in related research areas (pediatric chronic noncancer pain and pain in adult-onset cancer survivors) to indicate how the identified gaps and limitations can be addressed; and

(3) combine findings from aims 1 and 2 to provide a research and clinical agenda to guide future research on pain in childhood cancer survivors.

2. Review of empirical literature

Two authors (N.M.A. and M.M.G.) independently completed searches of PubMed, PsycInfo, and Google Scholar.

A systematic review was not conducted as the goal of this topical review was to draw attention to this area and guide future research. 

2.1. Overview

An observational case-control approach was used by 21 of the identified studies, wherein a cancer survivor cohort was compared with either siblings or healthy controls.

Over half consisted of samples sizes >700.

Nearly one-third were conducted as a part of the Childhood Cancer Survivor Study (CCSS), a large multi-institutional cohort study of childhood cancer survivors

When reported, mean age of survivors ranged from 15 to 37 years, and mean time since diagnosis from 10.2 to 26 years

Pain was defined and assessed in a multitude of ways, resulting in reports of general pain (eg, bodily pain, headaches) and cancer-related pain, wherein participants reported specifically about pain they attributed to cancer or its treatment.

2.2. Prevalence of pain

When reported, pain prevalence was influenced by pain severity and location, and cancer and patient characteristics. Prevalence of pain across studies ranged from 5% to as high as 59%.

Over half of the investigations did not report prevalence rates.

Younger age at diagnosis was associated with higher and lower risk of pain

Results were inconsistent regarding whether survivors experienced more pain than controls.

When compared with siblings in the Childhood Cancer Survivor Study, Zeltzer et al Bowers et al., and Lu et al. identified pain as a more likely occurrence among survivors; however, Zeltzer et al. found this only to be the case for survivors of bone cancers and soft tissue sarcomas.

Conversely, investigations in Sweden and in the United States failed to find significant differences in pain reported by survivors and controls, and one investigation found that survivors experienced less bodily pain than controls.

2.3. Factors associated with pain

Fear about the future and increased cancer anxiety were also associated with cancer-related pain.

Anything so obvious about cancer as “fear about the future” or “cancer anxiety” will be associated with cancer-related pain because both are “associated” with cancer. I’m sure those fears are associated with all cancer, even if it’s not painful.

You could say the same about the hair loss or medical bills: both are logically associated with cancer pain, which can only come about if the patient has cancer.

Compared with sibling controls, survivors were at increased risk of suicidal ideation, whereas cancer-related pain and pain severity were observed as significant predictors of suicidal ideation.

It’s no surprise that increasing pain leads to increasing desperation and increasing desire to leave this life.

Pain was also associated with poorer health-related functioning, body image, and health-related quality of life.

Survivors reporting pain were more likely to experience symptoms of emotional distress.

Having pain is almost by definition emotionally distressing.

3.1. Developmental factors

This has implications for survivors because early injury to the developing nociceptive system (eg, undertreated pain) can permanently impact subsequent pain processing, including sensitization to future painful stimuli.

The current fad of undertreating pain is creating a wave of patients that will suffer increasing chronic pain as they age.

Moreover, chronic pain often presents in childhood and adolescence and continues into adulthood in individuals without cancer. Thus, it is highly likely that chronic pain that emerges during childhood or adolescence as a result of cancer or cancer treatments persists into adulthood.

These findings are of particular concern for survivors as they grow older because chronic pain has been observed in over 50% of children undergoing outpatient cancer treatment.

3.2. Treatment and procedure-related factors

Pain during cancer can be related to the underlying disease; however, most pain experienced by children with cancer is caused by the treatments (eg, chemotherapy, radiation, surgery), or procedures (eg, lumbar puncture, bone marrow aspiration, intravenous insertion, port access, blood work) themselves.

Many children with cancer undergo major and/or minor surgery, and several of the most common surgeries such as amputation, limb sparing, and thoracotomy have the greatest incidence of chronic postsurgical pain due to associated nerve damage, thereby increasing the risk of developing chronic pain into survivorship.

In addition, a suboptimal presurgical context, including elevated pain intensity or anxiety, or poor pain coping efficacy, is predictive of chronic postsurgical pain among children.

Radiation therapy is associated with persistent pain among survivors of adult-onset cancer, and indirect irradiation of the brain is associated with elevated risk of migraines and cancer-related pain among adult survivors of childhood cancer.

In addition, children receiving vincristine for acute lymphocytic leukemia commonly experience chemotherapy-induced peripheral neuropathy, which could persist into survivorship.

With respect to procedures, suboptimal pain management is common…

I find this absolutely shocking. I thought cancer pain was being spared from all these spurious limits on pain relief. People whose lives are in danger now must also suffer unrelieved pain while and after their cancer is treated.

Cancer patients are “held captive” by an indifferent healthcare system, focused on survival statistics and procedure profits, that forces them to suffer needless pain.

…and can lead to higher self-reported pain during subsequent painful procedures and increased pain sensitization later in life.

3.3. Health-related factors

Adult survivors of childhood cancer are at risk of developing health-related late effects including subsequent malignancies, chronic health conditions, frailty, sleep difficulties, and fatigue.

Subsequent malignancies carry the potential for acute and chronic pain in survivors, which may be further exacerbated by preexisting chronic pain due to other factors (eg, cancer treatments).

Similarly, pain experienced from chronic health conditions such as arthritis and diabetes could create a compounded effect of chronic pain in later adolescence and adulthood.

Moreover, survivors who develop chronic health conditions as a late effect of cancer treatments are at risk of emotional distress, including symptoms of depression and anxiety, which are associated with pain in the general population.

Should be “are CAUSED BY pain” instead of “associated with pain”. How are symptoms of depression and anxiety different from depression and anxiety themselves?

Someday, we will see a study showing that depression and anxiety are directly “caused by” pain, instead of these mealy-mouthed, carefully hedged statements about “associated with” pain.

With respect to lifestyle factors, survivors are less likely than controls to meet physical activity guidelines and more likely to have an inactive lifestyle, despite evidence showing that regular physical activity prevents and improves chronic pain.

Here, they manage to sneak in some patient blaming by saying those with chronic pain are less active (a finding) “despite evidence” that this might decrease pain. There’s a value judgment in the word “despite”, essentially saying “they should know better” which puts the blame on the patient.

In the real world, “knowing better” seems to do little to prevent all kinds of other human behavior, like overindulgences that also lead to severe health consequences, like obesity or heart conditions or lung cancer.

Yet only pain patients are consistently singled out for doing things “despite evidence”, like overdoing it when they are feeling good (not pacing themselves) or allowing themselves to be beaten down by the daily discouragements and fears of the future due to living with constant pain (now labeled as catastrophizing), or not exercising more because it’s just too painful.

Pain was primarily examined as a predictor of other outcomes, rather than a primary outcome in and of itself, highlighting the dearth of research on chronic pain in survivors of childhood cancer.

Moreover, no studies of interventions for pain were found.

This shows how little thought is given to pain among cancer researchers.

5. Research and clinical implications

Several lines of future research can be identified—many of which carry clinical implications for the treatment of chronic pain and long-term care of survivors.

First, there is room for improvement in the conceptualization and understanding of chronic pain in pediatric and adult survivors of childhood cancer. Our findings point to inconsistency in reported prevalence of pain among survivors

Second, longitudinal research is essential to the prevention goals recently outlined by researchers. Research tracking pain from diagnosis into survivorship is needed. We identified a lack of consensus on the relationship of pain to treatment- and diagnosis-related factors, and minimal research examining the association between health and lifestyle factors and pain

Clarification of the influence of such factors on the interpretation of pain throughout treatment and the likelihood that pain may become chronic into survivorship will help provide specific practice recommendations

Why are they only concerned with factors that affect the “interpretation of pain” and not the plain itself?