Rehabilitation and supportive care of pets with cancer

Introduction

Cancer represents a significant cause of mortality among adult dogs, accounting for up to 27% of deaths, and a similar trend is observed in cats 1,2. There is no doubt that diagnosis has been improved with new techniques facilitating cancer detection, and that there have been many recent advancements in healthcare which can help prolonging the life of a pet diagnosed with cancer. Tumor management in dogs and cats is multifaceted, requiring individualized treatment plans based on medical history, prognosis, caregiver preferences, and personal experience. Typically, interventions aim to control or delay disease progression through surgical removal of tumors and/or inhibition of cell proliferation via chemotherapy, radiotherapy, or immunotherapy. While certain cancers may be curable, treatment for advanced or aggressive types often focuses on making the disease chronic while preserving quality of life.

Patients undergoing cancer treatment may encounter adverse effects from the disease itself or its management, and timely intervention is of great importance to mitigate these effects and enhance overall well-being. Thus, rehabilitation and supportive therapies are integral components of oncological care and can be implemented at any stage – from diagnosis and treatment to end-of-life care.

The role of rehabilitation 

Rehabilitation of pets with cancer before, during and after treatment encompasses a range of physical and medical interventions aimed at enhancing functionality, alleviating pain, and improving quality of life (Figure 1). This is primarily achieved through supportive care, which is focused on preventing or reducing both tumor-related symptoms and treatment-related side effects. In early (and sometimes chronic) stages, such care may include the administration of intravenous fluid therapy, blood products, analgesia, assisted feeding, and physiotherapy.

During chemotherapy, antiemetics are often used to prevent nausea and vomiting, while appetite stimulants or probiotics can help mitigate diarrhea or changes in stool consistency. Antibiotics may also be prescribed to reduce the risk of secondary infections during neutropenic periods. 

In later phases of cancer treatment, recurrence or metastasis may occur, and palliative treatment is then initiated to reduce tumor-related complications and provide comfort in advanced or end-of-life stages 3.

Both supportive and palliative care may complement each other or overlap in certain phases of the disease, but they share a patient-centered approach. Such an approach ensures that the patient is treated as a whole by including two key characteristics: multidisciplinary care and shared decision-making with the owner. 

• Multidisciplinary care integrates pain management, prognosis discussions, nutritional support, comorbidity management, and bereavement support. For instance, osteoarthritis, a common comorbidity in elderly dogs and cats with cancer, may alter analgesic plans or prompt consideration of physiotherapy for mobility improvement. Similarly, some comorbidities such as liver or renal disease can impact chemotherapy drug metabolism, and should be considered when making a treatment plan.
• Shared decision-making is crucial when informing owners about the treatment expectations, costs and the level of commitment, ensuring that therapy is individualized based not only on the pet but also client´s needs and preferences. Open, compassionate communication fosters a collaborative approach to care, optimizing outcomes and client satisfaction.

Pain management

Cancer-related pain may arise from the tumor itself (Figure 2) or as a side effect of treatment (Table 1). Pain can significantly impact mobility but also mortality, making accurate diagnosis and localization of pain critical when managing cancer patients. In dogs and cats with advanced or inoperable cancers, a common concern is chronic, undertreated pain, possibly leading to the sensitization of the central nervous system. In these cases, pain is not associated with tissue damage but with altered pain modulation that generates nociplastic pain (pain arising from altered nociception) 4. Educating owners about this risk allows them to monitor for behavioral changes at home, and this collaboration also facilitates a proactive approach, allowing clinicians to intervene earlier in the disease process and mitigate ongoing noxious input. 

Table 1. Main causes of pain in cancer patients.

Due to the complex changes induced in the sensory system, chronic pain is often managed with multimodal therapy. A tiered approach is generally recommended, with options that have the most evidence-based medicine, such as COX-inhibiting and non-COX-inhibiting (e.g., the EP4 receptor antagonist, grapiprant) drugs used first. In cases where these are contraindicated or pain persists, second-tier drugs may be added, such as gabapentin, paracetamol, and amantadine 4. Prednisolone may be considered (after a wash out period if NSAIDs have been used) in patients with steroid-responsive tumors such as lymphoma, leukemia and mast cell tumors, or in patients with brain and spinal tumors, with the aim to decrease peritumoral edema and inflammation. Third-tier drugs are generally reserved for refractory or severe pain; these include opioids such as tramadol and oral buprenorphine.

The addition of locoregional nerve blocks to the analgesic plan may also be considered for short-term pain control. However, good knowledge of the anatomy and the injection technique, sometimes with the aid of ultrasound guidance, is needed (Figure 3).

Other non-pharmacological strategies include palliative surgery for large, ulcerated, or bleeding tumors (Figure 4), palliative radiotherapy (e.g., for primary bone tumors or bone metastasis), environmental modifications, acupuncture, and the addition of omega-3 in the diet due to its anti-inflammatory properties.

A particularly painful cancer is primary or metastatic bone cancer. The pathophysiology of tumor-induced osteolysis is complex, but it is generally accepted that this is mediated by osteoclasts either activated by tumor cytokines or indirectly by osteoblasts. Intravenous bisphosphonates are known to be potent inhibitors of bone resorption and have been successfully used to treat osteosarcoma and tumors invading or metastatic to the bone in dogs and cats. The recommended dose (for both species) of pamidronate is 1-2 mg/kg given over a 2-hour infusion every 3-4 weeks, whilst for zoledronate it is 0.1-0.25 mg/kg up to a maximum of 4 mg, given as 15-minute infusion every 3-4 weeks 5,6.

The development of new analgesics and non-pharmacologic treatments holds promise. An example is bedinvetmab, a monoclonal antibody (mAb) against nerve growth factor (NGF). Endogenous levels of NGF are known to be increased in humans with cancer and a significant therapeutic potential of mAbs has been shown in experimental models 7. In addition, anti-NGF mAb may provide significant relief of bone cancer pain and slow the progression rate of tumor growth. Although further evidence is needed in dogs and cats with cancer, the author considers its use for dogs with osteosarcoma and in cats with osteoinvasive oral squamous cell carcinoma 7.

Frequent reassessment of analgesic requirements can be done by observing the pet’s behavior during clinic visits, monitoring physiological variables (heart rate, blood pressure), by tumor palpation, home videos and activity monitoring. Clinical metrology instruments (CMIs) can also help to assess the effectiveness of the implemented drugs, although a limitation of current CMIs is that available scales have been validated for musculoskeletal pain (osteoarthritis) and are not specific for canine or feline cancer patients. Examples of these scales include the Canine Brief Pain Inventory scale for chronic pain assessment in dogs (https://www.vet.upenn.edu/docs/default-source/VCIC/canine-bpi.pdf) and the Feline Grimace Scale in cats (https://www.felinegrimacescale.com/).

Nutritional considerations

After diagnosing cancer, veterinarians are frequently asked whether dietary adjustments should be made. This concern among pet owners was reaffirmed by a recent survey-based study, which found that 25% of owners altered their dog’s primary diet within six months of a cancer diagnosis 8. Nutritional intake in pets with cancer is frequently compromised for several reasons, including changes in food preferences and treatment-related side effects. Appetite alterations are a common concern, with studies reporting a wide range of incidences (17-76%) in dogs depending on the chemotherapy drug used. Additionally, it is well known that chemotherapy can induce changes in taste and smell 9. Early pharmacological intervention from the onset of clinical signs is essential, including the use of appetite-stimulating drugs such as maropitant, mirtazapine, metoclopramide, glucocorticoids and cyproheptadine 10. The development of novel drugs and routes of administration such as mirtazapine transdermal ointment shows promise for managing anorexia and weight loss in cats.

A new ghrelin receptor agonist, capromorelin, has received FDA approval in the USA for use in dogs and cats. The solution, dosed at 3 mg/kg orally q24H, has been shown to cause increased food intake and weight gain in both healthy laboratory and inappetent client-owned dogs 11. Similarly, capromorelin at 1-3 mg/kg q24h caused sustained increases in bodyweight and IGF-1 in cats 12.

Additionally, cancer can disrupt various mediators such as inflammatory cytokines, cortisol, catecholamines, insulin, and glucagon, leading to metabolic dysregulation. This may result in the utilization of muscle aminoacids as a primary energy source over fat, potentially leading to cancer cachexia-anorexia syndrome 13,14. Cachexia is defined as loss in lean body mass, and has been shown to correlate with prognosis in several human cancers. Similar associations have been found in pets with cancer; one study noted that although the prevalence of cachexia in dogs with cancer was low (4%), 69% of dogs had experienced some weight loss, and 35% had mild to severe muscle wasting 15. A study in cats reported cachexia in 6% of cases, while muscle loss was seen in 91% of affected cats 16. Additionally, cats with large cell lymphoma that lost ≥ 5% body weight after one month of chemotherapy treatment had significantly shorter survival times than those that gained or had stable weight 17. Another study assessed the effect of obesity on survival time in dogs with lymphoma or osteosarcoma; although no association between body condition score and survival time was found in animals with osteosarcoma, underweight dogs with lymphoma had significantly shorter survival times than those that maintained or gained weight 18.

The clinical impact of cancer anorexia-cachexia syndrome has increased the interest in developing new diets and drugs to enhance energy intake, increase nutrient absorption, and target metabolic pathways to reverse the catabolic effects, increase muscle mass, and enhance protein synthesis 14. Early detection of this syndrome can be challenging, but, when possible, individualized nutritional intervention can help slow progression and maintain a higher quality of life. For this reason, the dietary history should be carefully analyzed at each clinic visit, including any supplements being given, body condition and muscle condition scores. Based on the clinical concerns of the patient, the veterinarian should then ensure that the diet is complete and balanced.

For pets undergoing chemotherapy, additional considerations may need to be taken into account to promote gastrointestinal health and minimize drug side effects (Figure 5). These often include alterations in dietary fiber type and amount, and ensuring the diet offered has high digestibility. Supplementation with fish oil, which is high in omega-3 fatty acids, can also decrease inflammatory cytokine production and improve cachexia and food intake 19.

While nasogastric tubes are often used in the hospital setting, feeding though esophageal or gastrostomy tubes provide an effective method for long-term enteral nutrition at home. A nutritionally balanced, home-cooked diet formulated by a veterinary nutritionist is also an option, but these may be better reserved for later stages of the disease.

Table 2 summarizes some of the options available to help pets with cancer have an improved nutritional intake.

Table 2. Dietary considerations for pets with cancer that have altered appetite or cachexia (Adapted from 13).

Integrative medicine approaches

The use of acupuncture, cannabis products, massage, herbs, mushrooms and dietary supplements is increasingly popular among pet owners. However, concerns regarding the limited information about safety and efficacy are challenges for veterinarians when asked about these therapies, but a couple of comments are appropriate.

One of these alternative therapies is Yunnan Baiyao, a traditional Chinese medicine that enhances platelet function, but also has anti-inflammatory and anti-cancer properties attributed. Its exact herbal formula is a trade secret but due to increasing demand for quality assurance and the development of Good Manufacturing Practice the label now lists its major components. Yunnan Baiyao has been used adjuvantly to treat tumors with a bleeding tendency, such as visceral hemangiosarcoma and nasal tumors 20.

For pain management purposes, acupuncture and cannabidiol (CBD) oil are routinely considered at the author’s hospital as part of the multimodal approach to treating cancer. Acupuncture involves the insertion of needles in specific points on the skin (Figure 6), and its effects are partly mediated by a cascade of endorphins, monoamines and anti-inflammatory cytokines. Although there is limited evidence in veterinary medicine, acupuncture has mainly been used to treat pain. Some studies in human medicine suggest that it can also be beneficial in treating chemotherapy-induced nausea and vomiting, and may promote anticancer immunity 21,22.

CBD oil is also gaining attention due to its effects on the cannabinoid type 1 and 2 receptors, which, in addition to possibly stimulating appetite, have been attributed to have anti-inflammatory, analgesic, antioxidant, antiemetic, and immunomodulatory effects, among others. CBD oil has also been studied for its antineoplastic properties alone or in combination with chemotherapeutic drugs, with promising results 23. A recent study showed that CBD induced autophagy and apoptosis in vitro in canine osteosarcoma, mammary carcinoma, and B-cell lymphoma cell lines, justifying the need for clinical trials 24. The main barrier to its clinical use is the need for further pharmacokinetic data in these species and whether interactions could occur with other medications, including chemotherapeutic drugs 23,24.

Challenges to overcome

There is an increasing need for evidence-based medicine to evaluate treatment efficacy in pets undergoing supportive and palliative care. This entails using adequate study designs, delineating clear and specific endpoints, and using quantifiable outcome measures. Furthermore, there is a growing importance to develop tailored scales to monitor quality of life and chronic pain in pets with cancer.

Conclusion

Cancer treatment should integrate rehabilitation procedures throughout, from diagnosis to end-of life stages. Early intervention can improve quality of life and reduce short-term mortality. Increased awareness of the needs of these patients can significantly aid veterinarians to anticipate tumor and treatment-related complications.