So what exactly is happening in there that prevents us from jumping right back into life the day after treatment ends? There are several interrelated drivers of our need for some recovery time, including continued healing from the assaults of treatment, ongoing imbalances of metabolism, hormones, and cytokines, and general deconditioning. In addition, the psychological impact of these lingering issues keeps most folks in a state of ongoing stress, further exacerbating the symptoms.
Under the best circumstances, physical healing takes time. The evidence of a simple cut on the finger may disappear within a couple of weeks, but the average surgical scar is not considered fully healed for six months to a year. It takes that long for the body to make the right kind of cells, bring them to the right place, grow the appropriate vascular structure to support them, and remove and reprocess unnecessary scar tissue.
Similarly, chemotherapy and radiation cause side effects that take time to heal. Although both treatments target rapidly dividing cancer cells, other cells that have a high rate of turnover, such as skin and mucus membranes, can be damaged too, increasing the need for healing and adding time to the recovery process. Radiation also has the potential to change the structure of skin and connective tissue in the area surrounding the target, and can affect the vascular structure of the tissue as well, giving the body still more repair work to do.
One of the tricks the body uses to prevent the spread of cancer is cellular senescence—essentially aging the cells and shutting down their ability to replicate. Senescence also plays a role in wound healing, preventing scar tissue from growing out of control. But cellular stress, including the stress of radiation and chemotherapy, can trigger excess senescence. And unfortunately, one of the side effects of cellular senescence is inflammation, meaning that more pro-inflammatory cytokines are released, which further increases fatigue. It can take months for the body to clear the excess senescent cells and for inflammatory markers to return to normal.
In addition to damaging tissue, treatment also attacks our fast-replicating blood cells, including platelets, red blood cells, and white blood cells. Platelets, which play an important role in tissue repair and regeneration, are killed off by chemotherapy and radiation—just when we need them most, they’ve gone missing. While we make billions of them every day, they have a life span of only ten to twelve days, so it can be tough on the body to play catch-up, which often results in bone pain as the marrow goes into overdrive.
Similarly, red blood cell counts can drop significantly, leading to decreases in circulating hemoglobin and an inability to provide sufficient oxygen to our muscles. More fatigue. Although doctors may postpone treatment for a week or more if blood cell counts dip too low, it’s not unusual to end treatment with a deficit of up to one-third of our usual healthy counts. We generate about 2.4 million new red blood cells every second, but that’s a small fraction of the 10 trillion or so we may have lost. Given that red blood cells last only for three to four months, there is constant turn- over, but it can be hard to build back the lost cells while maintaining daily turnover rates.
The immune system also takes a hit thanks to a significant die-off of white blood cells. (Treatment to suppress the immune system is one of the things doctors count on when preparing patients for stem-cell or bone-marrow transplants.) Since the immune system is the body’s actual mechanism for initiating homeostasis, it’s no surprise that when it’s not functioning at peak capacity, it can take time for metabolism and hormone balance and even circadian rhythms to reestablish norms after cancer and its treatment.
One cytokine produced by the immune system, transforming growth factor-b (TGF-b), helps regulate cell activity, including signaling when cells should grow, migrate, die, develop a blood supply, and do everything else we count on them to do. But TGF-b can promote increased inflammation rather than turning it down, further prolonging the imbalance and fatigue, and slowing the regeneration of cells necessary for healing. Meanwhile, those dreaded pro-inflammatory cytokines (see the Science Sidebar in chapter 3), so essential to healing but with the potential to drive sickness behavior and depression, are still working in overdrive. No wonder we don’t bounce back.
The Downward Spiral
Unfortunately, these deficits gang up on us to make the recovery process a slow, uphill battle. Even if we didn’t turn into total couch potatoes, there would be some deconditioning that happens due to the side effects of treatment. It’s highly likely that we suffered some—if not many—days of not feeling fully ourselves. As a result, there’s a good chance we didn’t maintain the level of activity we were used to before the diagnosis, whatever that baseline may have been, and so don’t end treatment with the level of robustness we previously thought of as “normal.” For most of us, the whole treatment period is a slow downward slope of deconditioning. No matter how determined we are to keep moving, we end up being a little—or a lot—weaker than we were at the beginning. Decreases in hemoglobin mean we have less energy and are less likely to feel like going for a walk, much less head to the gym, so we get progressively weaker. We give ourselves license to skip the walk, friends bring dinner (obviating the need for us to shop and cook), and we spend more time sitting and napping.
Studies have shown that in just twenty days of continuous bed rest, even young, healthy men lose 27 percent of their aerobic fitness, equivalent to aging thirty years. And reconditioning takes time. We need to rebuild hemoglobin levels, rebuild muscle strength, and rebuild the nutritional inputs that fuel muscles, which often are depleted during days of languid queasiness.
Human bodies work hard all the time to maintain a balanced metabolic rate. But with stress and illness, metabolic demand can increase as much as 40 percent, even if we are not exercising. At the same time, after months of altered appetite, we may not be achieving the same nutritional balance we had before. If we are at all malnourished at the time we are trying to heal, or are further stressed by infection or injury, organs may go into overdrive, borrowing protein and other nutrients from skin and muscles in order to function, contributing to weakness.
In addition, cancer and its treatment can result in disruptions to the endocrine system, meaning hormones are released at the wrong levels and at the wrong times of day, upsetting circadian rhythms, sleeping habits, and neuromuscular function. We are likely to experience these disturbances as difficulty sleeping, muscle aches and pains, cognitive impairment, and, yes, more fatigue.
All in the Head
These physical challenges take their toll on us emotionally too. Unfortunately, lack of physical activity can contribute to depression. In one study, physically inactive individuals were 45 percent more likely to be depressed than active ones. And there is a similar link between inactivity and anxiety. In addition to being less physically active, many of us tend to hibernate during cancer, limiting our social activity. And yet for most people, a decrease in social activity also can contribute to the stress reaction and depression, further heightening discomfort. While the systemic imbalances are physical, we experience those imbalances in our minds, making it hard to reverse the pattern.
For some of us, a couple of sunny days or a shared laugh or a well-timed hug is enough to start the upward climb toward physical and emotional recovery. But for others, the symbolic bell ringing at the end of chemo just isn’t going to do it. Many patients find they need antidepressants, stimulants, pain medication, counseling, and other kinds of support to get them out of their treatment funk, and just about all of us will need the one thing we never have enough of—time.