Radiation recall: A well recognized but neglected phenomenon

doi:10.1016/j.ctrv.2005.07.008

Cancer Treatment Reviews

Volume 31, Issue 7, November 2005, Pages 555-570

https://doi.org/10.1016/j.ctrv.2005.07.008 Get rights and content

Summary

Introduction

Radiation recall is an inflammatory skin reaction at a previously irradiated field subsequent to the administration of a variety of pharmacologic agents. Although skin has been the major site of radiation recall toxicity, instances involving other organ have been reported.

Materials and methods

Data for this review were identified by searches of Medline and Cancerlit. The search terms “radiation”, “recall”, and “toxicity” were used. References identified from within retrieved articles were also used. There was no limitation on year of publication and no abstract forms were included. Only articles published in English were taken into consideration.

Results

Idiosyncratic drug hypersensitivity phenomenon is a recent hypothesis which correlates best with the available facts at this moment. The phenomenon may occur days to years after radiotherapy has been completed. The majority of the drugs commonly used in cancer therapy have been involved in the radiation recall phenomenon. A mixed non-specific inflammatory infiltrate seems to be the common histopathologic criteria in previous published reports. Universally, corticosteroids or the use of non-steroidal anti-inflammatory agents, in conjunction with withdrawal of the offending agent, produce prompt improvement.

Conclusion

We propose to collect all future radiation recall phenomenon in a Rare Cancer Network database in order to augment our understanding of this rare reaction.

Introduction

Radiation recall is characterized by an inflammatory reaction within a previously irradiated volume after administration of certain promoting agents, such as antineoplastic drugs. It was first described with the antitumour antibiotic actinomycin D1, 2 but it has been observed with other classes of chemotherapy agents, including anthracyclines,3, 4, 5, 6, 7 alkylating agents,⁸ antimetabolites,9, 10, 11, 12 nucleoside analog,13, 14, 15 and taxanes.16, 17, 18, 19, 20, 21, 22, 23, 24 Nowadays other different classes of pharmacologic agents have also been involved in this inflammatory reaction as antituberculosis drugs and antibiotics,25, 26 tamoxifen,27, 28 simvastatin29, 30 and exposure to ultraviolet light31, 32 can also induce it.

Although skin has been the major site of radiation recall toxicity,³³ instances involving lung,23, 34, 35 esophagus,³⁶ small intestine,37, 38 muscle,14, 15, 39, 40 central nervous system,¹⁵ and head and neck have also been reported.41, 42

This phenomenon is well known but poorly understood. In this review article, all etiological hypotheses on this phenomenon are critically discussed, and available radiobiological evidence is presented. All prior publications regarding radiation recall dermatitis and recall in other sites are reviewed. In addition, we develop herein all radiation parameters, grading score, drug characteristics, and time intervals characterizing this phenomenon.

Section snippets

Biological basis

Augmentation of radiation effects on normal and neoplastic tissues by the administration of chemotherapeutic agents has been extensively studied. The increased therapeutic benefit from synergistic effects of radiation and chemotherapy is being exploited in concurrent or sequential administration of the antineoplastic drugs and radiation in many tumour systems.

One special class of the normal tissue reaction from combined radiation and chemotherapy is designated “radiation recall” when it is

Review of the literature

Data for this review were identified by searches of Medline and Cancerlit. End of literature search was December 2004. The search terms “radiation”, “recall”, and “toxicity” were used. References identified from within retrieved articles were also used. There was no limitation on year of publication and no abstract forms were included. Only articles published in English were taken into consideration.

Radiation recall reaction may involve almost every organ system including skin, mucous membranes

Radiation parameters

The associated radiation doses ranged from 10 to 81 Gy. No absolute radiation dose threshold is clear, but it is interesting to note that in the clinical case reported by Yeo et al.,¹⁶ the skin reaction occurred in only two of four regions of irradiated skin, i.e., where the skin doses were the highest (from 18.7 to 21.5 Gy). This is reflected in either the recall phenomenon disappearing or at least diminishing with dose reduction; however, the radiation dose required to elicit recall has yet to

Conclusion

Radiation recall phenomenon is a well-known phenomenon without radiation- and drug-specific characteristics, even if adriamycin and taxanes seem to be more associated with this reaction. The etiology appears to involve local drug hypersensitivity through the inflammatory cascade stimulation in a cellular sensitivity area. Further experimental data need to confirm this hypothesis. We propose to collect data on all future cases of radiation recall phenomenon in a Rare Cancer Network^®

Acknowledgments

The authors thank Ms. F. Godson for her excellent editorial assistance.

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COVID-19 vaccine-induced Recurrence of the Radiation Recall Phenomenon in the Laryngeal Mucosa Due to a VEGF Inhibitor
2022, Advances in Radiation Oncology
The radiation recall phenomenon (RRP) is a rare and unexpected late complication of radiation therapy (RT). Although predominantly in the skin, RRP of the upper respiratory tract has also been reported. In general, RRP is caused by anticancer agents, and the COVID-19 vaccine has also been reported to cause RRP in recent years.
A 50-year-old woman who had received RT around the larynx 3 years prior and was receiving a docetaxel + ramucirumab (RAM) regimen experienced recurrent sore throat. The administration of RAM was discontinued after a gastroscopic examination revealed mucosal bleeding from around the larynx, which was thought to be RRP caused by RAM, a vascular endothelial growth factor inhibitor.
After the remission of the RRP, the patient received a COVID-19 vaccine (Pfizer-BioNTech). Five days later, the appearance of cough and recurrence of sore throat worsened with time, and marked stridor was observed. The patient was admitted, and steroid pulse therapy was administered for 3 days starting on day 18 after vaccination. On day 50 after vaccination, edema of the vocal cords improved.
When administering COVID-19 vaccines, considering that these vaccines may cause RRP is important, because RRP can be fatal in patients with a history of RT in the laryngeal region and treated with vascular endothelial growth factor inhibitors.
Radiation recall dermatitis induced by COVID-19 vaccination in breast cancer patients treated with postoperative radiation therapy
2022, Breast
and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients.
Patients that received at least one COVID-19 vaccination dose during the year after the end of postoperative breast radiation therapy were included in this observational monocentric study. Local symptoms occurring inside the radiation field after vaccination were patient-reported and scored according to the PRO-CTCAE questionnaire. Descriptive data of radiation recall dermatitis incidence and severity, and potential risk factors were evaluated.
A cohort of 361 patients with 756 administered COVID-19 vaccinations was analyzed. Breast symptoms were reported by 7.5% of patients, while radiation recall dermatitis was considered for 5.5%. The incidence of radiation recall dermatitis per single dose of vaccine was 2.6%, with a higher risk for the first dose compared to the second/third (4.4% vs 1%, p = 0.003), especially when administered within the first month after the end of irradiation (12.5% vs 2.2%, p = 0.0004). Local symptoms were generally self-limited and a few cases required anti-inflammatory drugs.
Radiation recall dermatitis is an uncommon but not rare phenomenon in breast cancer patients that received COVID-19 vaccination within one year after breast irradiation. However, symptoms severity were generally low/mild and reversible. These findings can be useful for patient counseling.
Integrating radiation therapy with targeted treatments for breast cancer: From bench to bedside
2022, Cancer Treatment Reviews
Major advances have been made in precision medicine of breast cancer patients with a series of molecular targeted therapies now in clinical use or in late clinical development. These new therapeutic measures need to be integrated with local treatments, particularly with radiation therapy in both curative and advanced settings. Although a synergistic effect could be obtained between targeted therapies and irradiation, potential safety concerns should be carefully considered. At present, scarce evidence exists due to a lack of quality assurance on radiation therapy in pivotal trials of new drugs and missing reports on safety in case of concurrent radiation therapy, commonly administered with heterogenous doses and fractionations, especially in advanced disease. A major contribution for effectively combining radiation and targeted therapies in breast cancer could derive from clinically relevant preclinical studies.
This review integrates preclinical and clinical evidence on how targeted agents and radiation therapy could be combined to help physicians in their daily clinical practice and to improve the clinical management of patients.
Radiation recall reactions: An oncologic enigma
2021, Critical Reviews in Oncology/Hematology
Radiation recall reactions (RRR) are uncommon but are a well-known phenomenon to oncologists. Tissue damage in a prior irradiation portal is ‘recalled’ after the administration of a drug, historically cytotoxics, or more recently, targeted or immunotherapeutic agents. Even COVID-19 vaccines are a reported cause.
RRR are enigmatic in that their cause is unknown, but they generally have the histopathological and clinical features of acute or chronic inflammation. They can occur in a variety of tissues, the commonest being skin, which accounts for two-thirds of reported cases. They are generally relatively mild and self-limiting once the trigger drug is stopped, although severe cases with tissue necrosis have occurred. Rechallenge with drug does not necessarily cause reactivation of the reaction. Symptomatic treatment with steroids and antihistamines are usually effective, but their impact on the clinical course is unclear.
Various hypotheses have been proposed as to the mechanism of RRR; a non-immune fixed drug reaction-like condition, dysregulated release of reactive oxygen species, abnormalities of tissue vasculature and impaired DNA repair. All could lead to a characteristic inflammatory microenvironment, resulting in dysfunction of tissue stem cells, keratinocyte necrosis and dermal abnormalities. Alternatively or in addition, low levels of inflammatory tissue cytokines induced by previous irradiation might be further upregulated by drug exposure.
Most information in this review refers to data derived from cutaneous RRR, since they are the most common form reported.
A Case of Radiation Recall Myositis and Neuropathy in Locally Advanced Rectal Cancer
2021, Advances in Radiation Oncology
: Neoadjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy has historically been the preferred approach to locally advanced rectal adenocarcinoma. Radiation recall reaction (RRR) is a rare complication which occurs in a previously irradiated region of a patient following initiation of systemic therapy. Myositis as a RRR toxicity is an even more rare phenomenon. We report a case of a patient with locally advanced rectal cancer who experienced myositis and neuropathy limited to the lower extremities during the adjuvant chemotherapy phase of treatment for rectal cancer.
: Our patient is a 57-year-old male with Stage IIIB low rectal adenocarcinoma who underwent standard neoadjuvant treatment with capecitabine and pelvic radiotherapy (RT) to approximately 50 Gy. He underwent abdominal perineal resection one month after completion of neoadjuvant therapy. Adjuvant FOLFOX began 5 weeks after surgery and was planned for eight cycles. Prior to his 4^th cycle, he developed weakness with hip adduction and extension and pain radiating from his hip down his anterior legs. These symptoms worsened despite dose reduction of his chemotherapy agents. He ultimately required a corticosteroid taper over 4 months and years of physical therapy to regain his lower extremity strength. After 5 years, his lower extremity pain persists.
: The onset, location, and quality of the myopathy and neuropathy in our patient cannot be explained by either RT or chemotherapy alone. Theories regarding the mechanism of RRR vary, but include subclinical tissue damage caused by RT which manifests only after additional toxicity from systemic therapy. Response to steroids is a hallmark of this condition. Early referral to physical therapy is also beneficial. Unfortunately, symptoms may not be fully reversible. The possibility of RRR myositis should be discussed with patients undergoing treatment for locally advanced rectal cancer.
Atypical radiation recall dermatitis induced by radiotherapy targeting a different site from the previously irradiated site
2024, Journal of Dermatology

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COMPLICATIONS OF TREATMENTRadiation recall: A well recognized but neglected phenomenon

Summary

Introduction

Materials and methods

Results

Conclusion

Introduction

Section snippets

Biological basis

Review of the literature

Radiation parameters

Conclusion

Acknowledgments

Int J Radiat Oncol Biol Phys

Lancet

Ann Oncol

Int J Radiat Oncol Biol Phys

Eur J Cancer

Lancet

Ann Oncol

Lancet

Clin Oncol

Int J Radiat Oncol Biol Phys

Am J Otolaryngol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

J Am Acad Dermatol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clin Oncol

Int J Radiat Oncol Biol Phys

J Am Acad Dermatol

Clin Oncol

Lancet

Ann Oncol

Gynecol Oncol

The effect of actinomycin D on cancer in childhood

Pediatrics

Clinical and biologic studies of actinomycin D and roentgen irradiation

Am J Roentgenol

Letter: adriamycin activating a recall phenomenon after radiation therapy

Ann Intern Med

Letter: uncommon side effects of adriamycin (NSC-123127)

Cancer Chemother Rep

Radiation-adriamycin interactions: preliminary clinical observations

Cancer

Doxorubicin-enhanced skin reaction after whole-body electron-beam irradiation for leukemia cutis

Mayo Clin Proc

Favorable response of metastatic osteogenic sarcoma to pulse high-dose methotrexate with citrovorum rescue and radiation therapy

Cancer

Combination chemotherapy and radiation therapy in the treatment of metastatic osteogenic sarcoma

Cancer

Radiation recall dermatitis induced by methotrexate in a patient with Hodgkin’s disease

Am J Clin Oncol

Radiation and 5-fluorouracil: a controlled clinical study

Radiology

Gemcitabine-induced radiation recall dermatitis: case report

Tumori

Docetaxel-induced radiation recall dermatitis and successful rechallenge without recurrence

Clin Oncol

Challenges in oncology. Case 2. Radiation recall associated with docetaxel

J Clin Oncol

Paclitaxel and radiation-recall dermatitis

J Clin Oncol

Radiation-recall dermatitis in a patient treated with paclitaxel

J Clin Oncol

COMPLICATIONS OF TREATMENT
Radiation recall: A well recognized but neglected phenomenon