Side Effects of Cancer Treatment (Cancer Surgery, Chemotherapy, Radiation Therapy)

Disease/Disorder

Definition

Over several decades, there has been a significant improvement in survival after cancer due to earlier detection and advances in surgery, chemotherapy, immunotherapy, and radiation treatment. Thus, the number of cancer survivors has grown to approximately 18.1 million as of January 2022 with that number projected to be almost 26 million by 2040.¹ Immediate and long-term impairments of cancer treatment are increasingly an issue that impact cancer survivors’ physical function and quality of life.

Etiology

Specific side effects of cancer treatment depend on different cancer/treatment variables such as type and length of treatment, tumor characteristics, disease stage, and severity. Patient variables such as age, comorbidities, baseline health and functional status may also play a role. Cancer and cancer treatments can cause a variety of functionally impairing complications including neuropathies, myopathies, tendinopathies, biomechanical changes, and metabolic/endocrine abnormalities. The list of possible complications is broad and varies with both tumor site and treatment approach. Due to the scope of this article, the more common complications of cancer surgery, chemotherapy, immunotherapy and radiation therapy will be discussed.

Epidemiology including risk factors and primary prevention

Complications after cancer surgery

General post-operative complications after cancer surgery can include pain, seroma or hematoma formation, adhesion formation limiting range of motion, and lymphedema. With regards to breast cancer, morbidity after breast or axillary procedures is reported to be between 3 and 50% and can include impaired shoulder range of motion (ROM), pain, lymphedema, chest tightness and brachial plexopathy.² Common complications after head and neck surgery include xerostomia (46% of patients), dysphagia (39%), hoarse voice (16%), neck pain (14%) and stiffness (10%).³ After colorectal cancer resection, 25-50% of patients are noted to experience bladder dysfunction, depending on the surgical approach.⁴ Approximately 21.1% of patients were reported to have low anterior resection syndrome, a constellation of symptoms including incontinence, frequency, urgency, or feelings of incomplete emptying.^5,6 Patients were also reported to have bowel incontinence at rates four times higher than the general population, in addition to sexual dysfunction.⁶ Prostate and gynecological cancer surgeries carry the risk of bowel, bladder, and sexual dysfunction, as well as infertility.⁷ Neurological complications reported in patients with brain tumors in the early rehabilitation setting include cognitive dysfunction (80%), motor dysfunction (78%), visuoperceptual deterioration (53%), sensory problems (38%), and bowel and bladder dysfunction (37%).⁸

Risk factors for post-operative complications after cancer surgery include patient-related variables such as obesity, baseline musculoskeletal or neurologic dysfunction, and lifestyle factors such as smoking, as well as treatment-related variables such as the extent of surgical resection, lymph node dissection, and adjuvant chemotherapy or radiotherapy.^2,4,8 Improvements in surgical technique and diagnostic modalities have been shown to reduce the risk of surgical side effects. Notably, the transition from axillary lymph node dissection (66% morbidity) to sentinel lymph node biopsy (36% morbidity) has significantly decreased the incidence of treatment-related sequelae.⁹ Advancements in surgical techniques have reduced the incidence of nerve palsies, such as long thoracic nerve injury during mastectomy, and have lowered the risk of spinal accessory nerve injury in selective and modified neck dissections compared to radical neck dissection.¹⁰ A major reduction in bowel and bladder difficulties and sexual dysfunction was noted with laparoscopic nerve-sparing gynecological surgeries.⁷ For many cancers, lymph node removal is a part of surgical treatment and carries the risk of lymphedema. One study demonstrated fluorescent sentinel lymph node mapping can confirm lymph node involvement in cervical cancer patients.⁷ Altogether, these advancements highlight how refined surgical approaches can significantly minimize complications and improve quality of life for cancer patients.

Primary prevention strategies emphasize minimizing surgical morbidity using less invasive or nerve-sparing techniques when appropriate, prehabilitation and early rehabilitation interventions, patient education, optimization of comorbidities, and supportive measures such as dental care and fertility preservation counseling.^4,6,8

Complications surrounding chemotherapy

The incidence and prevalence of chemotherapy related complications varies by chemotherapeutic agent and is typically dose dependent. Dose reduction is the only definite primary prevention strategy that can be generalized for these agents.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent long-term toxicities encountered in cancer survivors, with prevalence estimates ranging from 30–40% overall and up to 60% in those treated with taxanes, platinum compounds, or vinca alkaloids.¹¹ Taxane-induced CIPN occurs more commonly with paclitaxel (57%-83% with up to 33% being severe) than docetaxel (11%-64% with only 14% being severe).^12,13 Neurotoxicity of platinum agents ranges from virtually 100% for cisplatin to around 50% for carboplatin and oxaliplatin, with severe CIPN in 10% of patients.¹³ Oxaliplatin has unique cold-induced neuropathic features, while vincristine is particularly associated with motor and autonomic neuropathy. Vincristine-induced CIPN occurs in virtually 100% of patients, as opposed to other vinca alkaloids, such as vinblastine (8%) and vinorelbine (20%).^12,13 Risk factors include combination therapy with other neurotoxic agents, pre-existing peripheral neuropathy, low magnesium for platinum agents, and unrecognized hereditary peripheral neuropathy for vincristine.¹³ No definitive neuroprotective drug exists; preventive strategies include dose adjustments, avoidance of concurrent neurotoxic agents, cryotherapy (limb cooling) for taxanes, calcium/magnesium infusions for oxaliplatin (with mixed evidence), and early referral to rehabilitation. Exercise and physical therapy programs are increasingly studied as non-pharmacologic approaches to mitigate neuropathy-related disability.¹⁴ More recently, a recent study found that lithium (dosed at 2mEq/kg and given 1 hour prior) increases the survival rate of mice given high doses of paclitaxel, does not interfere with the antitumor effect of paclitaxel, and appears to prevent CIPN from taxanes.¹⁵

Anthracyclines remain a mainstay in breast cancer, lymphoma, and sarcoma treatment, but their use is limited by dose-dependent cardiotoxicity, with symptomatic heart failure occurring in 5–10% of long-term survivors and subclinical left ventricular dysfunction affecting even more.¹⁶ Risk is strongly tied to cumulative anthracycline dose (>450–550 mg/m² of doxorubicin equivalent), prior mediastinal radiation, female sex, older age, pre-existing cardiac disease, and concurrent use of trastuzumab.¹⁷ Prevention strategies include limiting cumulative dose exposure, use of liposomal formulations, administration of dexrazoxane as a cardioprotective agent in select patients, and close echocardiographic or biomarker monitoring.¹⁶ In rehabilitation settings, early integration of cardiopulmonary exercise programs can help maintain functional capacity and mitigate downstream deconditioning.

Bleomycin, a non-anthracycline antibiotic, is used to treat several types of cancer, including cervix and uterus cancer, head and neck cancer, testicle and penile cancer, and certain types of lymphoma. Pulmonary toxicity occurs in approximately 10% of treated patients, with risk of progression to pulmonary fibrosis, a complication that can cause chronic dyspnea and exercise intolerance in survivors.¹⁸ Risk increases with cumulative doses above 400 units, older age, pre-existing pulmonary disease, concurrent thoracic radiation, and exposure to supplemental oxygen during anesthesia.¹⁸ Preventive measures include strict cumulative dose limitations, pulmonary function testing before and during therapy, minimizing oxygen exposure during procedures, close monitoring for early respiratory symptoms, and pulmonary conditioning and energy-conservation strategies remain essential.

Hormonal therapies such as tamoxifen, aromatase inhibitors, and androgen deprivation therapy (ADT) are widely used in breast and prostate cancers, leading to accelerated bone loss, osteoporosis, and sarcopenia, which contribute to higher fracture risk and musculoskeletal pain syndromes in long-term survivors.¹⁹ Postmenopausal state, prolonged therapy duration, baseline osteopenia or osteoporosis, smoking, sedentary lifestyle, and low calcium/vitamin D intake increase risk. Preventive strategies include dual-energy x-ray absorptiometry (DEXA) scanning, calcium and vitamin D supplementation, pharmacologic use of bisphosphonates or denosumab, and incorporation of resistance and weight-bearing exercise programs.

Antimetabolite medications are typically used in breast, colorectal, stomach, and pancreatic solid tumors, as well as various leukemias. High-dose methotrexate, cytarabine, and, less commonly, other antimetabolites may cause leukoencephalopathy or cerebellar dysfunction, with an incidence of up to 10–15% in high-dose regimens, particularly in pediatric and CNS cancer populations.²⁰ Renal impairment (leading to delayed clearance), advanced age, cranial irradiation, and high-dose exposure are primary risk factors.

Treatment-induced thrombosis is a common adverse effect of some chemotherapy treatments. Tamoxifen can increase thrombotic risk, particularly in women with additional vascular comorbidities.²¹ Risk factors include older age, prior VTE, prolonged immobility, high-dose corticosteroid use, and hypercoagulable states. Preventive measures include routine anticoagulation prophylaxis (aspirin or low-molecular-weight heparin), risk stratification before initiation of therapy, and early mobilization strategies integrated into rehabilitation programs.

Musculoskeletal changes with radiation therapy

Radiation induced brachial plexopathy (RIBP) is thought to be caused by fibrosis of connective tissue around peripheral nerves, ischemia from damage to surrounding capillaries, and changes to axons (both myelinated and unmyelinated). There seems to be a direct correlation between doses per fraction of radiation and total dose of radiation. A recent meta-analysis showed that doses up to 60-66 Gray (Gy) are generally considered safe with regards to the brachial plexus, with a 5% risk of RIBP.²² Each 1 Gy increment is associated with a 1.11 relative risk increase in RIBP.²² Reducing the dose per fraction and total dose of radiation is the only primary prevention. More modern techniques in radiation therapy have been developed over time to help decrease radiation exposure of surrounding tissues and limit collateral damage such as intensity modulated radiation therapy (IMRT), gamma knife radiosurgery (GKRS) and proton therapy. An in-depth discussion of radiation techniques is outside the scope of this review. Radiation fibrosis syndrome (RFS) refers to fibrotic sclerosis that can result from radiation treatment due to abnormal accumulation of fibrin in both the intravascular and extravascular compartments.¹² The size of the radiation field, type, and susceptibility of underlying tissues to radiation play a pivotal role in the potential morbidity of radiation treatment.¹² Injection of botulinum toxin can be used for many complications of radiation fibrosis syndrome, including radiation-induced cervical dystonia, trismus, painful muscle spasms, and focal neuropathic pain disorders.¹²

Complications surrounding immunotherapy

Immunotherapy has transformed cancer care, particularly with immune checkpoint inhibitors (ICIs) and cellular therapies such as chimeric antigen receptor T cells (CAR-T). The incidence of immune-related adverse events varies by drug class, dose, and whether therapies are used in combination.²³ True primary prevention strategies remain limited. Instead, clinicians should focus on baseline assessment and surveillance, such as checking thyroid and adrenal function, liver enzymes, and cardiac biomarkers, and educating patients to promptly report new symptoms. In the context of CAR-T therapy, where cytokine release syndrome (CRS) and neurotoxicity are frequent, preventive strategies include stepwise dosing, close inpatient monitoring, and rapid access to cytokine blockade with agents such as tocilizumab.²⁴

Other side effects of cancer treatment

Side effects of cancer treatment, such as fatigue, sleep disturbances, cognitive changes (“chemo brain”), and malnutrition, can significantly impact daily functioning; a rehabilitation physician can help manage these symptoms through tailored interventions that support recovery and improve quality of life.

Patho-anatomy/physiology

Postoperative issues after cancer surgery

Impaired shoulder ROM may be a result of pain, surgical scarring, or axillary web syndrome (AWS), a series of cord-like structures palpable beneath the axillary skin because of the disruption of lymphatic vessel and veins. Decreased ROM in the shoulder can also be attributed to the length of pectoralis minor muscle.²⁵ Pain is often the result of soft tissue damage, nerve injury (e.g., intercostobrachial nerve), and scarring of tissues of the chest wall. Lymphedema occurs after damage to the lymphatic system. Bowel, bladder, and sexual dysfunction can occur in setting of low anterior resection syndrome due to internal anal sphincter dysfunction, decrease in anal canal sensation, disappearance of the rectoanal inhibitory reflex, and disruption of other local reflexes.⁵ Xerostomia, dysphagia, hoarse voice, and neck pain and stiffness can be due to removal of or damage to bone, muscle, cartilage, salivary glands, or nerves. Cancer surgery can sometimes result in unintentional injury to nearby structures, particularly when wider margins are required, but this may be necessary to achieve complete tumor removal and optimize patient outcomes.

Mechanisms of chemotherapeutic agents

Chemotherapeutic agents target rapidly dividing cells through diverse molecular mechanisms such as DNA damage, microtubule disruption, or inhibition of nucleotide synthesis as described in Table 1. Understanding these mechanisms is essential for physiatrists and oncology rehabilitation specialists because they directly influence the type, timing, and severity of treatment-related complications. Familiarity with these mechanisms also aids in anticipating functional impairments, designing safe rehabilitation programs, and guiding multidisciplinary care planning.

Mechanisms of radiation tissue damage

While not completely known, it is hypothesized that radiation causes tissue damage by free radical-mediated deoxyribonucleic acid damage and apoptosis, causing vascular endothelial damage, abnormal accumulation of thrombin, proliferative fibrin production, and subsequent sclerosis and progressive tissue fibrosis.²⁸

Mechanisms of immunotherapy adverse events

Immunotherapy augments the immune system’s capacity to recognize tumor cells but also carries the risk of unintended autoimmune responses. Immune-related adverse events differ from those seen in other anticancer regimens and can occur in any organ or organ system. The biological basis of immunotherapy toxicity is multifactorial. In ICIs, removal of inhibitory checkpoints unleashes T-cell activity, which promotes tumor clearance but can also trigger immune attack on healthy tissues.²⁹ Proposed mechanisms include molecular mimicry, epitope spreading, and bystander activation of immune cells.²⁹ B-cell–driven autoantibody production and cytokine cascades further amplify tissue injury.²⁹ In CAR-T therapy, CRS stems from a massive release of proinflammatory cytokines(most notably IL-6)while immune effector cell–associated neurotoxicity syndrome (ICANS) reflects disruption of the blood–brain barrier and diffuse cerebral inflammation.^30,31

Table 1. Major Chemotherapeutic Classes, Mechanisms of Action, Organ Systems Affected, and Common Cancer Types^{26, 27}

Copyright: Arman Jahangiri, DO. Aslihan Sahin, DO. Erin Kelly, DO.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Progression of postoperative cancer surgery morbidity

Postoperative complications and functional impairments vary depending on cancer type and surgical procedure. Below are common morbidities observed across different cancer surgeries:

Breast cancer⁹

• Axillary web syndrome (AWS) often develops in the early weeks after breast surgery and is generally self-limiting.
• Timely treatment of acute postoperative pain may reduce the risk of developing chronic pain and shoulder impairment.
• Up to 28% of patients have pain at three months post-surgery
• Persistent pain is found more commonly in patients with
  • Higher pain scores 6 hours post-surgery
  • Preexisting chronic pain
• Transient lymphedema can occur as a single episode lasting <3 months that resolves without treatment; lymphedema that lasts >3 months is considered chronic

Gynecologic cancer

• Severe pain in the immediate post-operative period was predictive of a higher risk of persistent postsurgical pain.³²

Prostate cancer³³

• Complications after radical prostatectomies (RP) can include
  • Erectile dysfunction (11-87%)
  • Urinary incontinence (0-87%)
• The highest rate of recovery is within the first year after RP.

Head and neck cancer

• Possible postoperative sequelae include³⁴
  • Dysphagia, dysphonia, trismus, and facial or neck muscle weakness
    • Hypoglossal nerve damage can cause temporary or permanent dysarthria and oral phase dysphagia
  • Shoulder syndrome (denervation of the upper trapezius causing pain, weakness, scapular dyskinesis, and shoulder girdle deformity) due to spinal accessory nerve injury in 47-100% of patients after radical neck dissection.
• Post-operative physical therapy programs can be helpful in reversing weakness and reducing post-operative pain.

Colon cancer⁶

• Bowel dysfunction may result from iatrogenic injury to neurovascular structures during surgery.
• There is no clear evidence that bowel function improves over time following surgery.

Brain tumors

• Approximately 1/3^rd of patients undergoing a craniotomy for tumor resection can have new or worsened neurological deficits within the first 5 days after surgery.³⁵
• Cognitive changes in memory, attention, and executive function may be transient or persistent.

Progression of chemotherapy-induced complications

CIPN is dose-dependent and often develops during certain chemotherapy treatments. Taxanes cause stocking-glove sensory loss and dysesthesias that may “coast,” continuing to worsen for several weeks after therapy cessation.³⁶ Oxaliplatin produces a distinct acute cold-triggered neuropathy within hours to days of infusion, which is often transient, followed by a chronic axonal sensory neuropathy that worsens with repeated dosing.³⁷ Vinca alkaloids, particularly vincristine, tend to involve early motor and autonomic fibers, producing distal weakness and foot drop that can accumulate with additional cycles.³⁸ Symptoms typically improve within the first 3-6 months after cessation of chemotherapy; however, recovery is often incomplete (20%-35%).¹³ Symptom progression may also continue for 2-6 months after cessation of therapy (the “coasting effect”) depending on the chemotherapeutic agent used.¹³ This phenomenon is seen most commonly in platinum-based agents, with cisplatin and oxaliplatin being the most common. Vinca-alkaloids and taxanes may also cause a coasting effect although this is less common.¹³ If used for prolonged periods at high therapeutic levels, the nervous system damage can be irreversible.³⁹ Development of neuropathy outside of the time course expected for taxanes, platinum analogues and vinca alkaloids should warrant investigation into other causes of neuropathy.

Cardiotoxicity

Anthracycline-related cardiotoxicity follows a well-characterized temporal pattern: acute toxicity occurs during infusion or within two weeks (manifesting as transient arrhythmias or pericarditis-myocarditis), whereas early-onset chronic toxicity develops within the first year and presents as progressive left ventricular dysfunction.¹⁶ Late-onset cardiomyopathy may manifest years to decades after therapy and is often irreversible once symptomatic heart failure appears.¹⁷

Pulmonary toxicity

Bleomycin can induce pneumonitis in weeks to months after exposure, beginning with dry cough and exertional dyspnea and potentially progressing to fibrosis if the drug is not discontinued.¹⁸ Once fibrosis forms, damage is largely irreversible, and survivors remain at lifelong risk of oxygen-exacerbated injury during anesthesia or supplemental oxygen therapy.¹⁸

Musculoskeletal toxicity

Hormonal agents such as aromatase inhibitors (AIs) and androgen-deprivation therapy (ADT) induce rapid bone mineral density (BMD) loss ~2–5% within the first year, followed by continued decline each subsequent year.¹⁹ Sarcopenia and body-composition changes emerge within 3–6 months of ADT initiation, increasing fall and frailty risk, while AI-associated arthralgias often begin within weeks to months of therapy and may persist throughout treatment. With appropriate pharmacologic and exercise-based interventions, bone loss can be attenuated but not fully prevented.¹⁹

Neurotoxicity

Methotrexate neurotoxicity can present as an acute or subacute encephalopathy (within days to weeks) characterized by confusion and executive dysfunction, or as delayed leukoencephalopathy appearing months after exposure, manifesting as slowed processing and memory deficits.²⁰ Another antimetabolite, cytarabine, causes a dose-related cerebellar syndrome consisting of ataxia, dysarthria, nystagmus, that arises during or immediately after treatment and typically improves over several weeks once the agent is discontinued, though residual ataxia may persist in older or renally impaired patients.²⁰

Thromboembolism

Tamoxifen-associated VTE risk increases soon after initiation and remains elevated throughout treatment, returning to baseline after discontinuation.¹⁹ Early pharmacologic prophylaxis and mobility programs markedly reduce the occurrence and chronic sequelae of VTE in these populations.

Progression of radiation therapy complications

Symptoms of RIBP often start with paresthesia, followed by pain and then development of motor weakness.⁴⁰ The effects of radiation can be acute (during treatment), early delayed (≤3 months after treatment), or late delayed (>3 months after treatment). RIBP is often a late complication of radiation therapy and is usually irreversible. Progression may lead to flail arm but the rate at which this happens varies. RFS can develop during radiotherapy or years later. Early symptoms may include mild stiffness and sensory changes, which can later progress to pain, weakness, and restricted range of motion. Progression of RFS is slow, and damage is irreversible. Rehabilitation strategies may help slow progression and preserve function in both RIBP and RFS.

Progression of immunotherapy adverse events

The timing and course of immunotherapy complications vary. For ICIs therapy, variable onsets have been described for the different toxicities, from early occurrence within days to delayed onset up to 26 weeks, with a median onset of approximately 40 days.²⁹ Of the ICIs, CTLA-4 inhibitors are more often linked with early events such as colitis or dermatitis, whereas PD-1 and PD-L1 inhibitors may cause later and more insidious toxicities, such as endocrinopathies, arthritis, and pneumonitis.²⁹ Myositis and myasthenia overlap syndromes can progress abruptly, sometimes within days, to bulbar weakness and respiratory failure.²⁹ Peripheral neuropathies may present more subacutely.²⁹ CRS typically appears within the first week and resolves with IL-6 blockade. ICANS, which often follows CRS, may resolve acutely but has been increasingly associated with prolonged neurocognitive deficits such as impaired attention, slowed processing, and executive dysfunction.³⁰

Essentials of Assessment

History

A comprehensive cancer-related history must include tumor type, tumor grade and staging, area of metastases (if any) and previous or upcoming cancer treatments. Knowledge of where certain cancers metastasize to is important for potential work-up when evaluating new pain or weakness Physiatrists should inquire about common cancer-related symptoms including fatigue, pain, and impaired ability to perform functional activities. From a surgical history perspective, the number of lymph nodes dissected, specific muscles sacrificed, and any reconstruction surgery should also be noted. Regarding chemotherapy and immunotherapy side effects, the type and dosing of the chemotherapeutic agent should be recorded, as well as the onset and characteristics of noticeable symptoms. When questioning about a radiation therapy history, it is important to understand the radiation field as vessels, nerves, and soft tissues structures in that area will be affected, and pre-existing neuromuscular and musculoskeletal conditions may also affect development of symptoms in the radiation field.²

Physical examination

A thorough musculoskeletal exam, including inspection of surgical scars or radiation burns, muscle atrophy, affected joint ROM, limb strength and sensation, and assessment of any swelling is essential to identifying postoperative and post-radiation changes. A neurologic exam, including strength, sensation, and reflexes should be performed, paying attention not only to loss of light touch and pinprick sensation, but importantly proprioception, because this may affect functional balance and gait. A comprehensive cognitive examination is essential for patients with a history of brain or cranial cancer, as it enables early detection of tumor or treatment-related cognitive impairments. Dermatologic evaluation of skin integrity is key when considering potential treatments (i.e., taping, splinting, compressive garments). A thorough head, eyes, ears, nose, mouth/throat (HEENT) exam will assess head and neck structures and function of the senses, such as an assessment of temporomandibular range of motion and associated muscle hypertonicity in the head and neck cancer population.

Functional assessment

The patient may self-report on impaired ability to perform self-care and mobility, or more standardized patient-reported outcome (PRO) measures (which will be subsequently discussed) may be used to assess function.

Laboratory studies

Specific laboratory studies should be tailored to the anticipated complications and acquired diagnoses during and after chemotherapy or immunotherapy. Hematologic monitoring with a complete blood count and differential, along with reticulocyte counts, is essential for detecting cytopenias. Renal function should be evaluated using serum creatinine, blood urea nitrogen, and a comprehensive electrolyte panel including potassium, calcium, phosphate, and uric acid, particularly in the setting of nephrotoxicity, tumor lysis syndrome, or immune-mediated nephritis. Hepatic injury can be identified through liver function tests, including AST, ALT, alkaline phosphatase, total and direct bilirubin, and albumin. Endocrinopathies associated with immunotherapy necessitate thyroid function tests (TSH, free T4), cortisol and ACTH levels, gonadotropin and sex hormone levels, and prolactin levels to assess for thyroiditis, adrenalitis, or hypophysitis. In addition, fasting glucose and hemoglobin A1c levels are important for monitoring immune-related diabetes, while lipid panels, electrolyte imbalances, and vitamin deficiencies may capture treatment-associated metabolic disturbances. Cardiac surveillance, particularly in patients at risk for chemotherapy-induced cardiomyopathy or immunotherapy-related myocarditis, should include BNP or NT-proBNP, troponin, and CK-MB levels when clinically indicated. Finally, inflammatory or autoimmune processes may be tracked with ESR, CRP, creatine kinase levels for myositis, and amylase or lipase for pancreatitis. If the initial inflammatory laboratory workup is equivocal, it would be prudent to pursue further rheumatologic workup.

Imaging

Magnetic resonance imaging (MRI) may be useful for identifying factors that contribute to morbidity after cancer surgery. In breast cancer, MRI can help evaluate brachial plexopathy or rotator cuff pathology associated with shoulder dysfunction. In brain cancer, it can detect complications such as pseudoprogression, hemorrhage, or venous sinus thrombosis. For head and neck cancers, MRI is valuable in assessing fistula formation or soft tissue necrosis. Additionally, MRI may help exclude concurrent degenerative spine conditions and differentiate these from disease recurrence or metastasis in patients with delayed symptom onset.

Computed tomography (CT) is often used to evaluate postoperative complications in gastrointestinal cancers, including bowel obstruction, abscess formation, or stricture. It can also assess fistulas or obstructions following gynecological surgery and detect urinary tract injuries related to prostate and other genitourinary cancers. CT scans are also valuable in assessing the degree of bony destruction, especially when cortical involvement raises concern for impending or actual pathologic fracture, and surgical fixation may be warranted. Given the complexity of these decisions, close collaboration with the patient’s oncology team is essential, especially regarding the role of positron emission tomography (PET) or other systemic imaging, which may be best ordered by the oncologist to guide both staging and treatment planning. In patients with cancer who are at risk for or have known bone involvement, osteoporosis, or who are on therapies that may affect bone health (such as aromatase inhibitors), bone mineral density testing with dual energy x-ray absorptiometry (DEXA) is critical in management of skeletal health and preventing catastrophic complications. A DEXA scan can help identify treatment-related osteoporosis and guide initiation of preventive therapies with agents like bisphosphonates or denosumab. Electromyography can identify characteristics of CIPN (motor or sensory involvement, axonal or demyelinating features) and diagnose RIBP and other lesions of the peripheral nervous system and musculature. Musculoskeletal ultrasound, used in conjunction with electromyography, can help evaluate injury or compromise neurovascular structures. Regarding safety of EMG in setting of lymphedema, there is no published evidence of infection as a complication of EMG; however, lymphedema can be considered a relative contraindication to performing needle EMG.⁴¹

Early predictions of outcomes

Regarding surgery, early full ROM and excellent wound healing are predictors of good outcomes. For CIPN, an earlier resolution of symptoms can be predictive of a better overall recovery of sensation and pain, because severe symptoms may persist for longer.¹³ Early predictors of favorable neurologic recovery include lower cumulative exposure, early recognition and prompt dose adjustment, and mild initial symptom severity.¹¹ Patients who experience transient or sensory-only neuropathy rather than motor or autonomic involvement typically show faster improvement, particularly when rehabilitation and exercise programs are implemented early.¹⁴ Early functional engagement such as gait training, balance work, and desensitization has also been associated with improved recovery and reduced chronic disability in CIPN.³⁶ Predictors of better cardiac outcomes include lower cumulative anthracycline doses (<400–450 mg/m²), absence of baseline cardiovascular disease, younger age, and normal left ventricular ejection fraction (LVEF) at treatment completion.¹⁶ Patients with early identification of subclinical pulmonary changes (decline in DLCO or new exertional dyspnea) and prompt cessation of bleomycin before radiographic fibrosis develop have a higher likelihood of full recovery.¹⁸ Better musculoskeletal outcomes are predicted by early exercise initiation, preserved baseline bone mineral density, normal vitamin D status, and absence of prior fractures or immobility.¹⁹ Favorable predictors for cognitive recovery after methotrexate or cytarabine exposure include younger age, lower cumulative doses, normal renal clearance, and early recognition of neurotoxicity with rapid dose modification.²⁰ For radiation effects, early full ROM and minimal skin burning may have a better outcome.

Professional issues

Assuring early access to rehabilitation interventions will ultimately improve the patients’ quality of life. Ongoing surveillance of rehabilitation needs, excellent relationships with surgical and medical oncologists, and effective communication skills are important for physiatrists in this field.

Rehabilitation Management and Treatments

Available or current treatment guidelines

A core panel of cancer rehabilitation experts supported by the American Cancer Society (ACS) published clinical practice guidelines for breast cancer rehabilitation, including pain management, fatigue, individualized exercise program recommendations, bone health, weight management, and CIPN.⁴² While specific to breast cancer, these guidelines can be used as framework for many cancer-related issues that span tumor type. The National Comprehensive Cancer Network has guidelines for clinical practice based on tumor type and common symptoms, such as pain and cancer-related fatigue.⁴³ The American Society of Clinical Oncology (ASCO) expert panels identify and develop practice recommendations for specific areas of cancer care. Foreign institutions and experts may also provide cancer or treatment specific practice guidelines for global points of reference, although caution should be exercised as certain interventions or treatments may not be available due to region specific barriers or governmental restrictions. The Society for Immunotherapy of Cancer (SITC) remains a good resource for practice guidelines regarding immunotherapy treatments for adverse events.

At different disease stages

Prehabilitation

Cancer prehabilitation is defined as the “process in the cancer continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment and includes physical and psychological assessments that establish a baseline functional level, identify impairments, and provide interventions that promote physical and psychological health to reduce the incidence and/or severity of future impairments”.⁴⁴ Prehabilitation for cancer patients is often multimodal, combining exercise, nutritional support, psychological stress reduction, along with other modalities.⁴⁵ Prehabilitation has shown improvements in functional and perioperative outcomes in colorectal cancer patients, in pulmonary function and walking tolerance in lung cancer patients, in fatigue, quality of life, and certain biomarkers in hematopoietic stem cell transplant patients, reduction of post-operative incontinence and preservation of muscle mass in prostate cancer patients, and improvement of upper quadrant function and lymphedema prevention in breast cancer patients.⁴⁵

Interventions for postoperative sequelae

Immediately after surgery, exercise precautions may be necessary to allow for wound healing.³ However, early referral to a structured and progressive physical therapy (PT) program can improve ROM and shoulder dysfunction after breast cancer surgery.⁹ Recent studies of supervised, progressive strengthening and aerobic exercise in breast cancer showed that exercise preserved aerobic capacity, improved self-esteem, and did not increase the incidence of lymphedema.^46,47 There is increasing evidence that exercise is beneficial, even in the palliative stage of cancer.⁴⁸ Physical, occupational, pelvic floor, lymphedema, and speech and swallowing therapy can help improve functional outcomes by restoring strength, coordination, and mobility in the affected muscles, reducing treatment-related complications, and enhancing patients’ ability to participate in daily activities, maintain independence, and improve overall quality of life. Physical, occupational, pelvic floor, lymphedema, and speech and swallowing therapy can help improve functional outcomes by restoring strength, coordination, and mobility in the affected muscles, reducing treatment-related complications, and enhancing patients’ ability to participate in daily activities, maintain independence, and improve overall quality of life. Several therapeutic injections may be helpful for patients experiencing pain after cancer surgery. Interventions such as intercostobrachial nerve block, serratus plane block, and neuroma injection may be helpful for neuropathic pain in the chest wall or axilla. Other nerve blocks such as stellate ganglion, celiac plexus, and ganglion impar blocks can help manage pain associated with head and neck, abdominal, or pelvic cancer treatment sequelae, respectively. Peripheral joint or bursa injections may be helpful for different musculoskeletal pathologies. Chemodenervation for radiation-induced spasm or dystonia, myokymia of the chest wall or shoulder musculature, trismus, sialorrhea, or limb spasticity may also be helpful.

Interventions for chemotherapy-related sequelae

The primary strategy to reduce chemotherapy-related adverse events is dose reduction or transition to a better tolerated agent if warranted. More specifically,
pharmacologic treatment with anticonvulsants (gabapentin, pregabalin, carbamazepine) and antidepressants (tricyclics, venlafaxine, duloxetine) can reduce neuropathic pain associated with CIPN.¹² ASCO’s updated CIPN guideline recommends duloxetine for painful CIPN (moderate strength), while no pharmacologic agent is endorsed for prevention; clinicians should emphasize dose modification/holds at first signs of neuropathy and utilize multimodal rehab/exercise for function.⁴⁹ Of note, for patients on tamoxifen therapy should avoid duloxetine initiation due to drug interaction inhibiting the metabolism of tamoxifen into its active form. Structured balance/gait training, progressive resistance/aerobic exercise, and desensitization strategies are recommended to mitigate disability; limb cryotherapy during paclitaxel infusions shows emerging benefit but remains non-standard in ASCO guidance.^14,49 There is mixed evidence on the role of natural products (i.e., vitamin E, glutamine, etc.) and complimentary therapies (i.e., acupuncture) to prevent and treat CIPN. TENS and acupuncture are both supported as generally safe by the National Comprehensive Cancer Guidelines.⁴³ Other compounds including a sigma-1 receptor and nicotinic acetylcholine antagonist in addition to cannabidiol (CBD) are currently under investigation for treatment of CIPN⁵. One recent preliminary study found that CBD dosed at 135mg/day reduced numbness/tingling and improved sensory function vs. placebo but did not affect pain and motor function.⁵⁰

For cardiotoxicity, the 2022 European Society of Cardiology (ESC) Cardio-Oncology Guideline recommends baseline risk stratification, surveillance with echocardiograms and cardiac biomarkers (troponin/NT-proBNP) in higher-risk patients, and dose limitation and/or liposomal anthracyclines when feasible.⁵¹ For pulmonary toxicity, best-practice recommendations emphasize early recognition of cough/dyspnea, drug cessation for suspected pneumonitis, and cautious use of systemic steroids in inflammatory phases; strict cumulative-dose limits, PFT monitoring (DLCO), and avoidance of unnecessary high FiO₂ are emphasized.¹⁸

For hormonal agents, the European Society of Medical Oncology (ESMO) and related society guidance recommend baseline and serial DXA, calcium/vitamin D, fall-prevention programming, pharmacologic bone protection (denosumab/zoledronic acid), and concurrent resistance and weight-bearing exercise.¹⁹

For neurocognitive and cerebellar toxicity, management centers on leucovorin rescue, aggressive hydration/urine alkalinization, cognitive rehabilitation, task-specific therapy, and balance/gait training.²⁰

ASCO recommend risk-adapted thromboprophylaxis for ambulatory patients with high-risk regimens, therapeutic anticoagulation for established VTE with extended (>6 months) therapy in ongoing cancer.⁵²

Interventions for radiation-related sequela

Rehabilitation should emphasize adaptive and compensatory techniques (such as stretching, strengthening, and manual therapy) that maximize strength, reduce pain, preserve function, and maintain mobility. Bracing or splinting may be useful to prevent contracture or aid in function in patients demonstrating significant weakness. Surgical treatments such as omentoplasty and nerve grafting have been reported to improve pain or weakness from RIBP but there is no current surgical standard of care⁴⁰. Although controversial, elective amputation is a consideration for chronic flail arm but may not reduce pain.

Interventions for immunotherapy-related sequela

During immunosuppression, it is important to have close monitoring and rapid recognition of toxicities. For relapse vigilance, educate patients to report red flags such worsening dyspnea/cough (pneumonitis), chest pain or new palpitations (myocarditis), bulbar symptoms (neuromuscular overlap), and coordinate rapid oncology re-evaluation.²³ For acute medical treatment, high-dose corticosteroids should be initiated initially. Additional interventions by organ system may be required. Neuromuscular complications may require escalation to IVIG and/or plasma exchange for myasthenic or fulminant overlap syndromes or early ICU/airway readiness for bulbar or respiratory involvement.²³ Cardiopulmonary toxicities may require cardiopulmonary monitoring and integration of orthostatic hypotension countermeasures (compression, salt/fluid strategies.²³ Endocrinopathies may require hormone replacement per endocrinology.²³ Rheumatologic adverse events may require Disease-Modifying Antirheumatic Drugs (DMARDs)/biologics selected with oncology input to preserve antitumor efficacy while controlling inflammation.²³ For CAR-T cellular immunotherapy per SITC guidance, standardized pathways exist for early tocilizumab (anti-IL-6) for CRS, while ICANS is managed with neuro checks, seizure prophylaxis as indicated, and steroids for higher grades.⁵³

Coordination of care

Effective interdisciplinary coordination is the cornerstone of cancer rehabilitation. Physiatrists serve as the bridge between oncology, surgery, radiation, nursing, and supportive care teams, ensuring that functional outcomes are integrated into the overall treatment plan from diagnosis through survivorship The ACS, Institute of Medicine, and other organizations have highlighted the importance of providing cancer survivors with the necessary resources to regain function and quality of life after cancer treatment.^28,54

Patient & family education

Comprehensive patient and caregiver education empowers survivors to recognize and manage treatment-related complications. Education should include precautions for altered sensation and neuropathy to prevent burns or falls (e.g., CIPN, RIBP), continued limb mobility and early exercise after surgery or radiation to prevent contractures and lymphedema, management of fatigue, energy conservation techniques, and pacing strategies during and after treatment, and guidance on nutrition, bone health, and safe participation in physical activity. Multimedia tools, tele-rehabilitation sessions, and survivorship handbooks can improve understanding and adherence.

Emerging/unique interventions

PRO measures have been developed for many cancer-specific issues. The Functional Assessment of Cancer Therapy (FACT) is a questionnaire developed to assess physical, social, emotional, and functional well-being in cancer patients, and has additional subscales available for specific tumor types and cancer-related impairments including fatigue, lymphedema, and neurotoxicity. It has now been expanded as Functional Assessment of Chronic Illness Therapy (FACIT). The Disabilities of Arm, Shoulder and Hand scale, the Simple Shoulder Test, and the Upper Extremity Functional Index are other tools specific to arm function. The BREAST-Q is a breast cancer surgery-specific tool used to assess chest, upper body, and trunk/abdomen dysfunction. The EORTC QLQ-C30 and Short Form 36 are used to assess quality of life in cancer patients.⁵⁵ The PROMIS Cancer Function Brief 3D Profile was recently developed and validated in outpatient cancer rehab patients.⁵⁶

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

To promote implementation, physiatrists should adopt standardized clinical pathways and participate in institutional quality initiatives focused on early referral and measurable functional outcomes. Performance improvement efforts might include embedding rehabilitation consult prompts in electronic order sets for high-risk populations, developing rapid-access “rehab triage clinics” within cancer centers, or participating in survivorship education for residents and oncology fellows to build cross-disciplinary awareness. Regardless of subspecialty interest, all physiatrists need to be educated on these skills as an increasing number of cancer survivors are seen throughout a variety of rehabilitation settings.

Cutting Edge/Emerging and Unique Concepts and Practice

Digital and tele-rehabilitation models enable ongoing functional monitoring and exercise supervision for patients in remote or rural settings. Neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and scrambler therapy show potential for managing chemotherapy- or immunotherapy-induced neuropathy and pain.⁵⁷ Integrative medicine modalities such as acupuncture, mindfulness, and yoga demonstrate modest but growing evidence for improving fatigue, anxiety, and CIPN symptoms. Cannabinoid-based therapies, though still investigational, may provide symptomatic relief for pain and insomnia in select patients when used under oncologic supervision.⁵⁸

Gaps in the Evidence-Based Knowledge

Despite significant progress, substantial gaps remain in cancer rehabilitation research and implementation. Evidence-based protocols for immunotherapy-related toxicities, radiation fibrosis, and long-term cardiopulmonary complications are limited. Prospective trials assessing the timing, intensity, and modality of rehabilitation across the cancer continuum are needed. Further, as survivorship extends into decades, physiatrists are uniquely positioned to lead studies examining late functional decline, secondary musculoskeletal syndromes, and neurocognitive recovery after novel therapies.⁵⁹

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Original Version of the Topic

Sarah M. Eickmeyer, MD, Gail L. Gamble, MD. Side effects of treatment (cancer surgery, chemotheraphy, radiation therapy). 12/28/2012

Previous Revision(s) of the Topic

Sarah M. Eickmeyer, MD, Michael Fediw, MD. Side effects of treatment (cancer surgery, chemotheraphy, radiation therapy). 9/15/2016

Kelsey Lau, DO, Jeffrey Barnett, DO, Michael Fediw, MD. Side Effects of Cancer Treatment (Cancer Surgery, Chemotherapy, Radiation Therapy). 1/12/2023

Author Disclosure

Erin Kelly, DO
Nothing to Disclose

Aslihan Sahin, DO, MBS
Nothing to Disclose

Arman Jahangiri, DO
Nothing to Disclose