How oncology therapies reshape peripheral circulation, nerve health, and tissue integrity—and why the feet serve as a diagnostic sentinel
By: Lennard M. Goetze, Ed.D / Phil Hoekstra, Ph.D
Introduction
Modern cancer therapies have transformed survival outcomes, yet survivorship often carries a hidden burden: long-term compromise of peripheral circulation, nerve integrity, and tissue resilience—most visibly expressed in the feet. Chemotherapy disrupts microvascular networks and damages peripheral nerves; radiation alters vascular regulation and autonomic signaling; and targeted and immunotherapies introduce new patterns of inflammatory and ischemic stress. These physiologic disruptions commonly manifest in the lower extremities as numbness, burning pain, edema, color changes, delayed wound healing, nail pathology, and skin breakdown—symptoms that erode mobility, independence, and quality of life.
PodiatryScan reframes the feet as a sentinel region for treatment-related injury—where early shifts in perfusion, nerve function, and tissue tolerance can be detected, monitored, and managed longitudinally. Rather than waiting for survivorship complications to escalate into disability, a proactive surveillance model identifies emerging microcirculatory compromise and neuropathic stress earlier in recovery. Positioned within oncology survivorship care, PodiatryScan supports preventive foot monitoring, rehabilitation planning, protective strategies, and timely referral—elevating post-cancer care from reactive management to function-preserving, anticipatory medicine.
1) Chemotherapy-Induced Peripheral
Neuropathy (CIPN) and the Feet
CIPN is among the most prevalent and functionally limiting toxicities of cancer therapy. Agents such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors damage sensory axons and small fibers that innervate the feet, producing numbness, paresthesia, burning pain, and proprioceptive loss. The feet—being distal—are affected earliest and often most severely. Sensory loss increases fall risk, impairs balance, and predisposes to unnoticed trauma. Persistent neuropathy can outlast treatment by years, reshaping gait mechanics and loading patterns across the foot and ankle. Surveillance that tracks sensory thresholds, skin integrity, and functional stability helps clinicians intervene with protective footwear, balance training, and timely referrals to neurology or rehab before secondary injuries accrue.
2) Microvascular Injury and Ischemic Stress
Many cytotoxic agents injure endothelial cells and disrupt nitric-oxide–mediated vasodilation, diminishing capillary perfusion in distal tissues. Reduced microcirculation compromises oxygen delivery to the toes and plantar skin, delaying healing after minor cuts or pressure points. In patients with pre-existing vascular disease, diabetes, or smoking history, treatment-related microangiopathy compounds ischemic risk. The feet, as terminal vascular territories, often reveal early signs of perfusion stress—color changes, temperature asymmetry, and delayed capillary refill—making them an ideal surveillance target for circulatory compromise during survivorship.
3) Radiation Effects on Vascular
Regulation and Autonomic Control
Radiation therapy can induce long-lasting endothelial injury, fibrosis, and autonomic dysregulation within treated fields and along neurovascular pathways. Although the feet are rarely irradiated directly, autonomic disturbances and systemic inflammatory responses can alter distal vascular tone and sweat gland function. Patients may report cold intolerance, color changes, edema, or brittle skin and nails in the lower extremities. These changes increase susceptibility to fissures, infection, and pressure injury—particularly in older adults or those with limited mobility. Monitoring distal tissue resilience becomes part of comprehensive survivorship care.
4) Hand–Foot Syndrome
(Palmar-Plantar Erythrodysesthesia)
Certain chemotherapies and targeted agents precipitate hand–foot syndrome, characterized by erythema, pain, swelling, desquamation, and blistering on palms and soles. Plantar involvement threatens ambulation and adherence to therapy. Early identification of plantar skin stress enables dose adjustments, topical protection, and offloading strategies that preserve function and reduce treatment interruptions.
5) Lymphedema, Edema, and Tissue
Vulnerability
Cancer-related lymphatic injury—whether from surgery, radiation, or systemic inflammation—can manifest as lower-extremity edema. Chronic swelling increases skin tension, reduces microcirculatory exchange, and raises infection risk. The feet, constrained by footwear and dependent positioning, are particularly vulnerable to maceration and fissuring. Longitudinal surveillance guides compression strategies, footwear modification, skin care, and referral to lymphedema therapy to prevent recurrent cellulitis and mobility decline.
6) Immunotherapy and Inflammatory
Dermatoses
Checkpoint inhibitors and other immunotherapies introduce novel inflammatory toxicities affecting skin and small vessels. Acral dermatitis, vasculitic changes, and microvascular inflammation may present on the feet as painful erythema, purpura, or ulceration. Differentiating immune-mediated dermatoses from ischemic or infectious etiologies is critical to avoid mismanagement and unnecessary treatment interruptions. Structured foot surveillance supports earlier triage and targeted management.
7) Nail and Skin Barrier
Disruption
Onycholysis, brittle nails, paronychia, xerosis, and fissuring are common during systemic therapy. On the feet, nail dystrophy alters pressure distribution in footwear, while skin barrier breakdown invites fungal and bacterial infection. Preventive foot care—routine inspection, nail management, moisturization, and footwear assessment—reduces secondary complications that disproportionately burden survivors with neuropathy or edema.
8) Musculoskeletal Deconditioning
and Gait Changes
Pain, fatigue, and neuropathy alter loading patterns across the forefoot and heel, precipitating callus formation, plantar fasciopathy, and stress reactions. Deconditioning compounds these biomechanical shifts, increasing fall risk. Integrating podiatric assessment with rehabilitation planning preserves mobility and helps survivors return to activity safely.
9) Infection Risk in an
Immunocompromised Host
Neutropenia and mucocutaneous barrier injury elevate the risk of tinea pedis, cellulitis, and wound infection in the feet. Minor interdigital fissures can escalate rapidly in immunocompromised patients. Proactive surveillance, patient education on daily foot checks, and rapid response pathways for early infection signs are essential.
10) Why the Feet Are a Sentinel in Survivorship
The feet concentrate the downstream effects of vascular, neurologic, inflammatory, and mechanical stressors introduced by cancer therapies. Because they are distal, load-bearing, and richly innervated, early dysfunction becomes clinically apparent there first. PodiatryScan operationalizes this insight through structured, longitudinal foot monitoring—integrating perfusion cues, sensory status, skin integrity, and functional mobility into survivorship workflows. The result is earlier detection, smarter referrals, targeted protection, and function-preserving care that keeps survivors mobile and independent.
Clinical
Takeaways
· Screen early and often for sensory loss, perfusion stress, and skin barrier compromise in the feet during and after therapy.
· Act preventively with footwear optimization, offloading, skin care, balance training, and timely specialty referral.
· Coordinate care across oncology, podiatry, neurology, rehab, and wound services to prevent small problems from becoming disabling sequelae.
References
1.
American Cancer
Society. (2023). Hand–foot syndrome (palmar-plantar erythrodysesthesia).
2.
Argyriou, A. A., Bruna, J., Marmiroli, P., & Cavaletti, G. (2012). Chemotherapy-induced peripheral neurotoxicity (CIPN):
An update. Critical Reviews in Oncology/Hematology, 82(1), 51–77.
3.
Cavaletti, G., & Marmiroli, P. (2010). Chemotherapy-induced peripheral
neurotoxicity. Nature Reviews
Neurology, 6(12), 657–666.
4.
Hershman, D. L., et al. (2014).
Prevention and management of chemotherapy-induced peripheral neuropathy in
survivors of adult cancers. Journal of Clinical Oncology, 32(18),
1941–1967.
5.
Lacouture, M. E., et al. (2011).
Clinical practice guidelines for the prevention and treatment of EGFR
inhibitor–associated dermatologic toxicities. Supportive Care in Cancer, 19(8),
1079–1095.
6.
National Cancer
Institute. (2024). Peripheral neuropathy (PDQ®)–Health professional
version.
7.
Rockson, S. G.
(2018). Lymphedema. American Journal of Medicine, 131(3), 276–280.
8.
Siegel, R. L., Miller, K. D., & Jemal, A. (2024). Cancer statistics. CA: A Cancer Journal for
Clinicians, 74(1), 17–48.
9.
Smith, E. M. L., et al. (2013). The
reliability and validity of a modified Total Neuropathy Score in patients with
CIPN. Journal of the Peripheral Nervous System, 18(1), 45–51.
10.
Sonis, S. T.
(2013). Pathobiology of mucositis. Nature Reviews Cancer, 4(4),
277–284.
