|Ahead of print
Oropharyngeal carcinoma in fanconi anemia patient - Radiation treatment, toxicity, and a year follow-up: Case report
Febin Antony, Jomon C Raphael, Mathew K Varghese, Paul Gopu
Amala Institute of Medical Sciences, Amala Nagar, Thrissur, Kerala, India
|Date of Submission||27-Feb-2020|
|Date of Decision||06-Apr-2020|
|Date of Acceptance||18-Jun-2020|
|Date of Web Publication||16-Jul-2021|
Jomon C Raphael,
Amala Institute of Medical Sciences, Amala Nagar, Thrissur, Kerala
Source of Support: None, Conflict of Interest: None
Fanconi anemia (FA) is an inherited bone marrow failure disorder. In patients with FA, there is a high incidence of head and neck squamous cell carcinoma (HNSCC). As there is a defective DNA repair mechanism, radiotherapy (RT) or chemotherapy has an increased risk of toxicity in FA patients with HNSCC. We report the radiation treatment for oropharyngeal carcinoma in a FA patient. Our patient was treated with RT to a total dose of 60 Gy in 30 fractions. She developed grade 3 oral mucositis, grade 3 neutropenia, and thrombocytopenia at 20 Gy which resulted in treatment break of 11 days. She again developed grade 3 mucositis, grade 2 dermatitis, grade 3 thrombocytopenia, worsening of odynophagia at 44 Gy which resulted in a treatment break of 19 days. She completed RT and is now disease-free for 1 year with a good quality of life.
Keywords: Fanconi anemia, head and neck squamous cell carcinoma, radiotherapy, toxicity
|How to cite this URL:|
Antony F, Raphael JC, Varghese MK, Gopu P. Oropharyngeal carcinoma in fanconi anemia patient - Radiation treatment, toxicity, and a year follow-up: Case report. Indian J Cancer [Epub ahead of print] [cited 2021 Jul 27]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=321669
| » Introduction|| |
Fanconi anemia (FA) is an inherited bone marrow (BM) failure disorder. In patients with FA, there is a high incidence of head and neck squamous cell carcinoma (HNSCC). As there is a defective DNA repair mechanism, radiotherapy (RT) or chemotherapy has an increased risk of toxicity in FA patients with HNSCC. There are a few case reports showing the variable clinical radiosensitivity and fulminant radiation toxicities even with low doses of radiation., We report the radiation treatment for oropharyngeal carcinoma in a FA patient without overt hematological manifestations. We are also reporting the RT related toxicities with a year follow-up.
| » Case History|| |
A 25-year-old woman presented with history of foreign body sensation in throat and odynophagia for a duration of 3 months.
At the age of 10, she was evaluated for pancytopenia and was diagnosed of FA by stress cytogenetics. She was advised hematopoietic stem cell transplantation, but due to personal reasons she could not undergo transplantation. She was on regular follow-up with hematologist.
On examination, she had microcephaly, short stature, abnormal skin pigmentations. Direct laryngoscopy showed 3 × 4 cm ulceroproliferative growth in vallecula involving the lingual surface of epiglottis and biopsy was suggestive of squamous cell carcinoma. Base line blood investigations were as follows: hemoglobin: 10.1 gm/dL, white blood cell count: 2500 × 103/μL, neutrophils: 54.5%, thrombocytes: 460 × 103/μL. Computed tomography (CT) soft tissue neck showed a growth in vallecula with no lymphadenopathy. Chest x-ray was normal. Thus, a diagnosis of carcinoma oropharynx cT3N0M0 (Stage III) was made. Case was discussed in multidisciplinary tumor board (MDT) and decided for definitive RT.
CT simulation was done with five-point ray cast with head in neutral position. Contrast-enhanced CT scan with 2.5 mm slice thickness was acquired; target volumes and organs-at-risk (OAR) were delineated. Radiation dose of 60 Gy to high-risk region (PTV 1) and 54 Gy to prophylactic neck region (PTV 2) was planned with simultaneous integrated boost technique. Volumetric arc technique was used to obtain a full coverage of planning target volume (PTV) with 95% isodose curve and to achieve dose constraints to OARs [Figure 1]a.
|Figure 1: (a) Initial PTV, (b) PTV after the first break in treatment (PTV: planning target volume)|
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After completing ten fractions of RT, she developed vomiting, worsened odynophagia. On examination she had grade 3 oral mucositis (radiation therapy oncology group). RT was withheld and was started on antiemetics, step 2 analgesics, and parenteral nutrition. Nasogastric tube was inserted to improve nutrition. She also had high-grade fever with grade 3 neutropenia and grade 3 thrombocytopenia (common terminology criteria for adverse events) which was managed with antibiotics and blood transfusion. She improved in the ward and after 10 days of treatment break, we decided to restart RT by reducing the treatment volume to high-risk region (PTV1) [Figure 1]b.
After completing 22 fractions, she developed fever and worsened pain which required a treatment break. On examination, she had grade 3 mucositis, grade 2 dermatitis, grade 3 neutropenia. She was started on antibiotics, step 3 analgesics, and supportive medications. After 19 days of break, we restarted RT by reducing the treatment volume to 1.5 cm margin around the tumor (PTV3) [Figure 2]. Thus PTV2, PTV1, PTV3 received 18 Gy, 44 Gy, 60 Gy respectively in 69 days.
|Figure 2: PTV after the second break in treatment (PTV: planning target volume)|
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Post-treatment, she was supported with parenteral nutrition, blood transfusion, and was discharged in 2 weeks after the completion of RT. Her feeding tube was removed one and half months after RT. She had regular follow-up at two months intervals and her last follow-up was in December 2019, indirect laryngoscopy showed normal mucosa. She is disease-free with good quality of life.
| » Discussion|| |
The unusual spectrum of solid tumors, with a preponderance of HNSCC in FA patients remains unexplained. Possible route to carcinogenesis is an interaction of the environmental toxins or viruses to the mucous membrane, with a constitutional deficiency to repair DNA damage consequent to the exposure. Though hematological malignancies are most associated with FA, previous reports also suggest these patients are predisposed to solid tumors, particularly HNSCC and that too at an earlier onset of age.
RT or chemotherapy for HNSCC has an increased risk of toxicity in FA patients due to defective DNA repair mechanism. As of now there are no standard guidelines regarding the total dose, dose per fractionation, technique in RT of HNSCC in FA patient.
Our patient is a 25-year-old woman with stage III oropharyngeal carcinoma; MDT decision was to offer her definitive RT. Considering the high morbidity due to impaired DNA repair mechanism and effect of BM suppression, concurrent chemotherapy was not offered. Literature review on total radiation dose, dose per fraction, number of fractions, total treatment days in HNSCC patients with FA ranged from 2500-7020 cGy, 170-200 cGy, 20-39 fractions, 31-70 days, respectively., Our patient received a total dose of 6000 cGy in 30 fractions which was completed in 69 days. Most common complications during RT were grade 3 mucositis, dysphagia, and hematologic abnormalities., Radiation mucositis was observed as early as 3.2 Gy in one of the case reports, whereas in another patient radiation was delivered without much toxicity. Our patient developed grade 3 oral mucositis, grade 3 neutropenia, and thrombocytopenia at 20 Gy which resulted in treatment break of 11 days. She again developed grade 3 mucositis, grade 2 dermatitis, grade 3 thrombocytopenia, worsening of odynophagia at 44 Gy which resulted in a treatment break of 19 days. Previously published case series consider pancytopenia as a major concern in managing post RT complications in these patients because it can precede to bleeding complications, fatigue, delayed wound healing, and infection. Our patient also had hematological complications that persisted even after completing RT which required blood transfusion and antibiotic support.
In our experience, we could conclude that RT in FA patient with HNSCC entails careful monitoring of the patient throughout the treatment period, as it may require multiple hospital admissions, blood transfusions, infection control, pain management, nutritional support, temporary break in treatment, target volume modification, and post RT complication management.
The authors acknowledge with gratitude the immense help given by Mrs. Minu Boban, Dr. Sunu Cyriac, Dr. Sreeraj V, Dr. P C Sudheeran, and Dr. Gopi Krishna MS, during all stages of the work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]