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Journal of Clinical Oncology, Vol 23, No 34 (December 1), 2005: pp. 8911-8913 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.02.7417
A Bayesian Approach to a Patient With a Residual Mass After Treatment for Non-Hodgkin's Lymphoma of the ThyroidFrom the University of New Mexico Cancer Research and Treatment Center University of New Mexico, Albuquerque, NM. Address reprint requests to Ian Rabinowitz, MD, University of New Mexico Cancer Research and Treatment Center, University of New Mexico, 900 Camino de Salud, NE, Albuquerque, NM 87131; e-mail: irabinowitz{at}salud.unm.edu HERE'S THE CASE A 51-year-old female with a previous history of Hashimoto's disease presented with a right neck mass. The mass was thought to involve the thyroid gland. An initial fine needle aspirate was nondiagnostic, but suspicious for lymphoma. An open incisional biopsy of the thyroid mass revealed a diffuse large B-cell lymphoma and surrounding thyroid parenchyma revealing chronic lymphocytic thyroiditis (Hashimoto's thyroiditis). The large neoplastic lymphoid cells were strongly CD 20 positive on immunohistochemical staining. Flow cytometry revealed that 15% of the cells were abnormal B-lymphocytes with CD 19, CD20, FMC7 expression and loss of immunoglobulin light-chain expression, consistent with a B-cell lymphoma. A computed tomography scan revealed a 3 x 5 cm mass that involved the thyroid as well as a 1 x 2 cm right supraclavicular node. A staging work-up, including a positron emission tomography (PET) scan and a bone marrow biopsy, determined that she apparently had disease localized to the neck, with only the thyroid mass and the supraclavicular node demonstrating fluorodeoxyglucose (FDG) uptake. She was treated with four cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, followed by involved-field radiation to the neck (41.40 Gy). After completion of this therapy, a firm, nontender 1.5 cm mass was still present in the right thyroid region. A repeat PET scan, performed approximately 6 weeks after the completion of the radiation, demonstrated that the thyroid mass had shrunk from 5 cm to 1.5 cm and that the supraclavicular node had disappeared. The thyroid mass was still avid for FDG uptake; no other areas of abnormality were noted. A presumptive diagnosis of residual lymphoma was made and the patient was scheduled to be admitted for reinduction chemotherapy to be followed by high-dose chemotherapy with autologous stem-cell support. DISCUSSION It is a basic principle in oncology to obtain a repeat biopsy when a patient has their first relapse after definitive therapy. This rule is especially valid when there is a single new lesion, and/or if there is a long interval between the time of the original cancer and the development of the new lesion. However, this principle is often ignored, due to perceived patient inconvenience, the risk of the biopsy procedure, or a resultant delay in initiating therapy. Although it is recognized that in the majority of cases the biopsy will merely confirm a relapse, in a certain percentage of patients, another diagnosis (a nonmalignant process or another cancer) will be obtained. The principle of obtaining a repeat biopsy is in greater jeopardy of being ignored with the advent of the PET scan.1
The clinical dilemma in this patient can be approached using Bayes' theorem:
In order to perform this calculation, pre-existing data comparable to this clinical situation were analyzed. A literature search of the rate of in-field failure for patients with non-Hodgkin's lymphoma (NHL) of the head and neck treated with radiation therapy (with or without chemotherapy) was performed (Table 1).2-8 Secondly, the sensitivity and specificity of PET scans in patients with treated NHL was extracted from available literature. All articles containing treated patients with Hodgkin's and NHL were included. However, only patients with NHL were extracted for this analysis (Table 2). 9-16 The patients in the studies were added together to obtain an average rate for each measured variable. Using an average in-field relapse rate of 5%, a PET scan sensitivity of 92%, and a false-positive rate of 5%, the above theorem yielded the following:
Using Bayes' theorem, after the positive PET scan result, there was only a 49% chance that the residual mass was due to refractory lymphoma. This is in contrast to the clinical impression that prevailed at the time the patient was being evaluated. Using Bayes' theorem, a biopsy would have been mandatory. Even without using quantifiable data (which is often difficult to extract in a timely manner in clinical practice), it is useful to bear in mind the principle of Bayes' theorem, namely that the pretest probability of a disease should impact the interpretation of the result of a test used to diagnose the disease. Although every attempt was made to use data specific for this exact clinical situation, this was not possible. Specifically, the PET scan data derived from Table 2 were not in patients with thyroid lymphoma treated with chemotherapy and radiation. However, these were all patients with NHL who had received either chemotherapy, radiation, or a combination of the two. It was judged that the value of the PET scan is determined by the tests' accuracy, which should be independent of the therapy used to eradicate the lymphoma. Determining the level of probability at which a biopsy would or would not be mandatory is a complex question. However, even if the probability is 90% for recurrence, is it justifiable to forego a biopsy and treat 10% of patients unnecessarily? It is the opinion of the authors that, in general, physicians should almost always obtain a repeat biopsy when a patient presents with an initial possible recurrence of a previously treated cancer. The risks of a biopsy are usually far less than the toxicity and risks associated with inappropriate treatment. Nonetheless, exceptions to this approach may include situations where the anatomic location is difficult to biopsy (eg, brain), where there are multiple lesions that make the pretest probability of recurrent disease very high, or if there are no planned therapeutic consequences of a diagnosis of recurrence. A biopsy is strongly recommended when a recurrence will result in an aggressive treatment such as in this case. THE CASE REVISITED Given this information, the patient subsequently had a fine-needle aspiration biopsy, revealing necrotic tissue. After much discussion between the patient and her treating physician, the patient had another biopsy of this mass whereby she was found to have a papillary carcinoma of the thyroid arising in a background of extensive nodular Hashimoto's thyroiditis. There was evidence of necrosis, but no residual lymphoma was identified. She subsequently underwent a thyroidectomy. No evidence of lymphoma was found in the surgical specimen. Pathologic review confirmed that the initial lesion was a lymphoma and also confirmed the newly diagnosed papillary carcinoma. This case should serve as a reminder to physicians to question the results of a study, especially when the pretest probability of a clinical situation is low. The results of such diagnostic studies should especially be questioned when it will have a major impact on patients' care. In this present case, the patient averted receiving high-dose chemotherapy and, instead, underwent a surgical resection of a thyroid tumor. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
NOTES This manuscript contains original material, which has not been previously presented and has been exempted from institutional review board approval as per the University of New Mexico Human Research Review Committee. Authors' disclosure of potential conflicts of interest are found at the end of this article. REFERENCES
1. Kazama T, Faria SC, Varavithya V, et al: FDG PET in the evaluation of treatment for lymphoma: Clinical usefulness and pitfalls. Radiographics 25:191-207, 2005 2. DiBiase SJ, Grigsby PW, Guo C, et al: Outcome analysis for stage IE and IIE thyroid lymphoma. Am J Clin Oncol 27:178-184, 2004[CrossRef][Medline] 3. Nathu RM, Mendenhall NP, Almasri NM, et al: Non-Hodgkin's lymphoma of the head and neck: A 30-year experience at the University of Florida. Head Neck 21:247-254, 1999[CrossRef][Medline] 4. Kuten A, Ben-Shahar M, Epelbaum R, et al: Results of radiotherapy in stage I to II extranodal non-Hodgkin's lymphoma of the head and neck. Strahlenther Onkol 165:578-583, 1989[Medline] 5. Goldwein JW, Coia LR, Hanks GI: Prognostic factors in patients with early stage non-Hodgkins lymphomas of the head and neck treated with definitive irradiation. Int J Radiat Oncol Biol Phys 20:45-51, 1991[Medline] 6. Ruijs CD, Dekker AW, van Kempen-Harteveld ML, et al: Treatment of localized non-Hodgkin's lymphomas of the head and neck. Cancer 74:703-707, 1994[CrossRef][Medline] 7. Briggs JH, Algan O, Miller TP, et al: External beam radiation in the treatment of patients with extranodal stage IA non-Hodgkin's lymphoma. Am J Clin Oncol 25:34-37, 2002[CrossRef][Medline] 8. Hoederath A, Sack H, Stuschk M, et al: Radiotherapy of primary extranodal non-Hodgkin's lymphoma of the head and neck region: Results of a prospective multicenter study—Study Group NHL: Early studies. Strahlenther Onkol 172:356-366, 1996[Medline] 9. Castellucci P, Zinzani PL, Pourdehnad M, et al: 18F-FDG PET in malignant lymphoma: Significance of positive findings. Eur J Nucl Med Mol Imaging 32:749-756, 2005[CrossRef][Medline] 10. Naumann R, Vaic A, Beuthien-Baumann B, et al: Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol 115:793-800, 2001[CrossRef][Medline] 11. Cremerius U, Fabry U, Neuerburg J, et al: Prognostic significance of positron emission tomography using fluorine-18-fluorodeoxyglucose in patients treated for malignant lymphoma. Nuklearmedizin 40:23-30, 2001[Medline] 12. Maisey NR, Hill ME, Webb A, et al: Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses? Eur J Cancer 36:200-206, 2000
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15. Zinzani PL, Magagnoli M, Chierichetti F, et al: The role of positron emission tomography (PET) in the management of lymphoma patients. Ann Oncol 10:1141-1143, 1999 16. Pauker SG: Clinical decision making, in Wyngarden JB, Smith LH Jr, Bennett JC (ed): Cecil's Textbook of Internal Medicine. Philadelphia, PA, WB Saunders, 1992, pp 68-73 Submitted May 20, 2005; accepted June 13, 2005.
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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