|Year : 2012 | Volume
| Issue : 3 | Page : 439-441
Gemcitabine-induced radiation recall phenomenon in a post-operative and post-radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy
Jayanta Biswas1, Sumita Dutta2, Shyam Sharma1, Krishnangshu B Choudhury1
1 Department of Radiotherapy, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Kolkata, West Bengal, India
2 Department of Anatomy, Medical College, Kolkata, West Bengal, India
|Date of Web Publication||17-Nov-2012|
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Source of Support: None, Conflict of Interest: None
Radiation recall phenomenon is an inflammatory process occurring at sites of previous radiation subsequent to administration of pharmacologic agents. The most common chemotherapeutic agents implicated with radiation recall phenomenon are anthracyclines and taxanes. Skin is the most common site for radiation recall. About 63% of the radiation recall events are reported to manifest as dermatitis. This finding differs from radiation recall due to Gemcitabine, in which approximately 70% cases manifested as inflammation of internal organs or tissues and 30% manifested as dermatitis. Here, we report a case of post-operative peri-ampullary carcinoma who developed radiation recall dermatitis during adjuvant chemotherapy with inj. Gemcitabine and inj. Carboplatin after concurrent chemoradiation with capecitabine.
Keywords: Anthracycline, capecitabine, carboplatin, chemotherapeutic agents, concurrent chemoradiation, gemcitabine, radiation recall dermatitis, taxane
|How to cite this article:|
Biswas J, Dutta S, Sharma S, Choudhury KB. Gemcitabine-induced radiation recall phenomenon in a post-operative and post-radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy. J Can Res Ther 2012;8:439-41
|How to cite this URL:|
Biswas J, Dutta S, Sharma S, Choudhury KB. Gemcitabine-induced radiation recall phenomenon in a post-operative and post-radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy. J Can Res Ther [serial online] 2012 [cited 2019 Nov 20];8:439-41. Available from: http://www.cancerjournal.net/text.asp?2012/8/3/439/103529
| > Introduction|| |
The literature search by Philip A. Friedlander et al. in the year 2004 found 13 cases of radiation recall caused by Gemcitabine, including their own reported case.  That study revealed gemcitabine-induced recall dermatitis in patients with breast and lung cancer, whereas pancreatic cancer presented with myositis.  Zouhair et al. proposed to collect all future radiation recall phenomenon in a Rare Cancer Network database in order to augment understanding of this rare reaction.  To enhance the knowledge regarding this phenomenon, we are reporting this case of recall dermatitis induced by Gemcitabine in a patient of peri-ampullary carcinoma. We could not found any Gemcitabine-induced recall dermatitis with figure reported from India in the literature.
| > Case Report|| |
A 53-year-old female with complaints of progressive jaundice and colicky abdominal pain of 2 months duration underwent ultrasonography (USG) of abdomen which revealed dilated common bile duct (CBD) and intra-hepatic billiary radicles (IHBR) with distended gall bladder (GB). Abdominal computed tomography (CT) scan was suggestive of a nodular mass lesion in lower bile duct near ampulla with the obliterated biliary system, likely peri-ampullary neoplastic mass. A magnetic resonance cholangio-pancreatogram (MRCP) also revealed moderately dilated IHBR, CBD 22 mm; stricture in distal CBD near ampulla; papilla appears bulky; main pancreatic duct (MPD) was normal. An upper gastrointestinal (GI) endoscopic biopsy from ampullary growth was suggestive of infiltrating adenocarcinoma. The operative findings of Whipple's operation were distended GB; mass palpable in the peri-ampullary region, duodenal lumen, no involvement of superior mesenteric artery or vein (SMA/SMV), enlarged aortocaval, retropancreatic, common hepatic lymph nodes, no ascites, no peritoneal deposits. Histological diagnosis was moderately differentiated adenocarcinoma of peri-ampullary-duodenal type extending full thickness of duodenal wall and up to head of pancreas. One out of three lymph nodes showed metastasis. Resection margins were free. Pathologically Stage T3 N1 M0. She received post-operative concurrent chemoradiation-45 Gy in 25 fractions over 5 weeks with image-guided radiotherapy (IGRT) with concurrent oral capecitabine 500 mg three times daily. Subsequently, she received adjuvant chemotherapy with intravenous inj. Gemcitabine 1.4 g on day 1 and day 8 and intravenous inj. Carboplatin 450 mg on day 2 of 21 days cycle, total of 6 cycles.
The patient was uneventful till 5 th cycle of chemotherapy. After day 8 of 5 th chemotherapy schedule, the patient had developed peculiar maculo-papular rash [Figure 1] surrounded by erythematous edge exactly over the pre-irradiated site (which was covered with thermoplastic immobilization mask during radiotherapy) and there was no other skin reaction in other parts of the body with no fever. There was no response after 2 weeks of combination of oral amoxicillin and clavulanic acid and third-generation cephalosporin antibiotics. She underwent fine-needle aspiration cytology (FNAC) to exclude recurrence. The lesion was confirmed to be of non-specific inflammatory in nature. An USG of abdomen showed no recurrence of the tumor, rather suggested non-specific skin and sub-cutaneous tissue inflammation. Culture report from overlying fluid showed no organism after 72 h of incubation and microbiology report for acid fast bacilli (A.F.B) and fungal element were also negative. Topical steroids were initiated and the lesion disappeared dramatically within 7 days of starting the drug. Sixth cycle of chemotherapy was given after the lesion had subsided. Interestingly, there was no recurrence of symptoms this time.
|Figure 1: Peculiar maculopapular rash over the previously irradiated site on the epigastrium|
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| > Discussion|| |
Radiation "recall" dermatitis resembles severe sunburn at a previously irradiated site with the administration of offending pharmacologic agent.  It is normally a self-limiting reaction without long-term sequelae. The reaction often includes maculopapular eruptions, vesicle formation, and skin desquamation. Approximately 63% of the total radiation recall events manifested as a dermatitis.  But occasional cases were noted in the muscle, lungs, bowel, esophagus, central nervous system, and vulva. The time interval from the completion of radiation therapy to the development of radiation recall phenomena reportedly varies from weeks to years. There are cases of radiation recall dermatitis reported to have developed as soon as 8 days and as long as 15 years after radiation therapy.
The incidence of radiation recall phenomenon has been underestimated. Tan et al. presented the only data on the incidence, in which 47% of pediatric patients developed radiation recall dermatitis triggered by actinomycin D.  A retrospective epidemiological study on incidence of radiation recall in a community cancer center reported radiation recalls in 13% of 334 patients treated with radiation.
Initially it was reported in 1959 with actinomycin D. Subsequently, radiation recall reactions have been attributed to a wide range of cytotoxic agents.  These include taxanes (paclitaxel and docetaxel), anthracyclines (doxorubicin and idarubicin), cytarabine, bleomycin, capecitabine, vinblastine, etoposide, methotrexate, trimetrexate, edatrexate, melphalan, dacarbazine, oxaliplatin, dactinomycin, hydroxyurea, 5-fluorouracil (5-FU), and interferon-α. Other noncytotoxic agents such as simvastatin, isoniazid, rifampin, pyrazinamide, and tamoxifen also have been implicated. ,,
In 1999, Welsh et al. published the probable first report of a recall event attributed to gemcitabine.  In the literature search by Friedlander et al., out of the 13 reported cases of Gemcitabine-induced radiation recall, only 4 (31%) manifested as a dermatitis or mucositis, whereas approximately 70% of the cases involved inflammation in internal tissue or organs. Therefore, although the majority of radiation recall cases involving the two most common inciting agents (i.e., taxanes and doxorubicin) manifest as a dermatitis or mucositis, the vast majority of reported cases involving gemcitabine occur in the internal tissue/organs. 
The exact mechanism of radiation recall dermatitis is poorly understood. The recent hypothesis indicates an idiosyncratic drug hypersensitivity phenomenon. It has been suggested that the initial radiation therapy leads to a depletion of tissue stem cells within the irradiated field and the subsequent cytotoxic exposure causes a "remembered" reaction among the remaining surviving cells.  Seymour et al. suggested that radiation-induced mutations might contribute to this phenomenon in the surviving cell population.  Treatment is symptomatic; and application of topical corticosteroids and use of non-steroidal anti-inflammatory agents is usually effective.  The withdrawal of offending agent causes dramatic improvement.
This patient developed radiation recall dermatitis after 5th cycle of chemotherapy with gemcitabine and carboplatin. There is very little experience about rechallenging with the exciting agent. In this case, after the lesion subsided, we administered 6 th cycle of chemotherapy, but interestingly there was no reaction this time. The phenomenon being mostly idiosyncratic in nature may probably explain the reaction only with the 5 th cycle of chemotherapy.
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