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Abscopal Effect



Study - Experimental Model for the Irradiation-Mediated Abscopal Effect and Factors Influencing This Effect

"We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT."

Case study - An interesting case of possible abscopal effect in malignant melanoma. 

Unfortunately I could not get the full text of this article, but I could at least get a summary. The patient experienced remission from late stage melanoma after having a wide excision, lymphangiogram and radiation to his inguinal (groin) region. However, unfortunately he had a sudden severe rectal hemorrhage after one year (I suspect it's likely due to the radiation) and passed away.   

"The natural history of malignant melanoma is notoriously unpredictable. Although long term survival is not uncommon, lymph node involvement lowers the five yr survival rate to about 5%. It is generally accepted that radiation has no place in the treatment of metastases despite occasional reports of temporary tumor regression. In these cases the response to irradiation occurred in the treated area and simultaneous regression of distant untreated metastases has never been reported. Such behavior has been given the term 'abscopal effect'. It occurs not uncommonly in leukaemia but is extremely rare in other tumors and the case reported is therefore of interest. The patient was a 28 yr old male, who had had a melanoma on the lateral side of the right knee for many years. A wide excision of the melanoma with a skin graft was performed. A lymphangiogram carried out on the right leg showed extensive involvement of the glands in the right inguinal region, with abnormal lymphatic channels in the pelvis. There was failure to fill the right lumbar chain, with deviation of the contrast into the grossly abnormal left lumbar chain. The patient was treated with a full course of fast neutrons (1,440 rad in 12 fractions over 35 days) to the right inguinal region. The upper medial limit of the field was the inferior border of the right sacroiliac joint. A repeat lymphangiogram showed a remarkable regression from the initial very abnormal picture and nine mth after treatment was started, the lymphangiogram was normal. At laparotomy no metastases were found, either in the iliac or para aortic nodes. He remained clinically free of disease during one year when a sudden severe rectal haemorrhage resulted in his death. At post mortem there was no evidence of residual metastatic melanoma."

Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma  

This was published in 2012, not long after the observed patient experienced regression but not remission from her melanoma, after receiving both ipilimumab and radiation treatments. I have not seen any follow-up to learn of her long-term outcome.

(Brain metastases specifically)

Case Report of Extended Survival and Quality of Life in a Melanoma Patient with Multiple Brain Metastases and Review of Literature  

The patient had melanoma found in her neck (a mass) and a scalp lesion. She had a biopsy which proved the scalp lesion was melanoma and surgery to remove the mass. That same month they found on a PET scan on the other side of her neck hypermetabolic activity and she underwent surgery to remove 28 lymph nodes (including 3 that tested positive for melanoma); the surgery left positive margins (cancerous cells were left in the surgical site). She had two additional excisions of other scalp lesions. Then she received radiation to her scalp and neck, followed by three cycles of cisplatinum, interferon, and vinblastine, then interleukin-2. 9 months after completing the therapy they found a nodule in her retroperitoneum and 3 brain metastases. She had gamma knife radiation to the brain lesions and stereotactic ablative radiotherapy (SABR) to a pelvic soft tissue metastasis. The following months she received four cycles of carboplatin, paclitaxel, and temozolomide treatment. Three months following those treatments she developed headaches, nausea, vomiting, and confusion due to growth of the tumor and edema. Temodar was discontinued and she was given steroids. Subsequent scans revealed regressing disease until remission. As of 2017 she had perfect cognition and was running marathons, 11 years after diagnosis!!

"Notably, this patient never underwent craniotomy or whole brain radiation therapy and, consequently, avoided the related long-term neurocognitive toxicity of these interventions... We present a patient who is recurrence-free 11 years after the diagnosis of three brain metastases. Her treatment consisted of cytokine (interferon and interleukin-2) and chemotherapy nine months prior to developing brain and soft tissue metastases, which were treated with stereotactic radiosurgery and stereotactic ablative radiotherapy, respectively, followed by six months of chemotherapy. Notably, she has not received any treatment for over 10 years, never underwent craniotomy or whole brain radiation therapy, currently has a perfect score on the functional assessment of cancer therapy for brain (FACT-Br) quality of life (QoL) scale, and runs marathons. This treatment course is consistent with emerging literature on the abscopal effect (radiation-induced immune response). Clinical trials are needed to better understand and harness the abscopal effect in order to optimally integrate targeted drug and radiation therapies."   

In this study they reference other long-term survivors who received:

a) Interferon, SRS, two craniotomies, chemotherapy 

b) Craniotomy, vaccine, SRS 

c) SRS, two craniotomies, chemotherapy

I haven't been able to check these case histories out yet but they are referenced for the above survivors:

- Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis. BMC Cancer. 2015, 23:926–931. 10.1186/s12885-015-1927-0 

- Pulmonary sarcoid-like granulomatosis after multiple vaccinations of a long-term surviving patient with metastatic melanoma. Cancer Immunol Res. 2014, 2:1148–1153. 

- Multiple brain metastases from malignant melanoma with long-term survival. Br J Neurosurg. 2004, 18:552–555. 10.1080/02688690400012616  

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