Imaging in Oncology

Imaging in Oncology (Answer)

Answer:

1. residual mediastinal tumor

Discussion

A negative gallium scan following treatment strongly predicts successful outcome in patients with an initially positive scan. Clearly, in patients with negative (non-avid) pretreatment scans, negative scans following treatment are of no value. A positive gallium scan following intensive therapy is consistent with an ominous prognosis. Karimjee et al¹ studied a small group of patients with mediastinal Hodgkin’s disease and obtained gallium scans six weeks following therapy. In three patients who had positive studies, two relapsed within four months. As part of a restaging protocol, Front et al² performed gallium-67 scintigraphy within four months of completion of therapy in a group of 99 lymphoma patients. Among patients with Hodgkin’s disease, a positive gallium scan had a positive predictive value (PPV) of .80 vs a PPV of .29 for CT. The difference in disease-free survival between patients with positive scans and those with negative gallium scans was significant (P<.05) at a mean followup of 22.8 months.

A number of groups have proposed the use of gallium scanning to tailor therapy in patients undergoing complex treatment protocols. The group from Duke University Medical Center has described results among 33 retrospectively identified patients with advanced disease studied with planar gallium scans following combination chemotherapy and immediately prior to postchemotherapy-involved field consolidation radiotherapy.³ Twelve of 13 patients with positive gallium scans relapsed -- 10 at the site of increased gallium uptake. The mean interval to relapse was six months. Two of the 30 scan-negative patients relapsed, one in the groin and one at the elbow, at a mean interval of 25 months. The four-year actuarial disease-free survival and overall survival were 75% and 100%, respectively, for patients with negative scans vs 8% and 51%, respectively, for those with positive scans (P=.001). The authors conclude that patients with advanced disease whose gallium scans remain positive following chemotherapy should be diverted from consolidation radiotherapy and should undergo a more aggressive salvage therapy protocol.

Investigators at the M.D. Anderson Cancer Center reached a similar conclusion when they prospectively sought prognostic factors among 46 patients (three were excluded because of negative initial scans) with stage I-III Hodgkin’s disease who were treated with a strategy of clinical staging and combined modality therapy.⁴ Here too, single-photon emission CT (SPECT) scans were obtained following chemotherapy and prior to radiotherapy. No pretreatment clinical characteristic (eg, B symptoms, bulky disease, hilar disease, extent of infradiaphragmatic disease) was predictive of relapse. Relapse occurred in only one of 33 patients with negative gallium scans but in three of 10 with positive scans. Complete remission rates and three-year progression-free rates were 70% for patients with positive gallium scans compared with 100% for those with negative gallium scans (P<.02). These authors also point out that since the radiotherapy delivered after the positive scans did not eliminate their adverse implication, alternative treatment strategies should be considered for these patients.

The interpretation of gallium-67 images can be even more treacherous among these treated patients than others. Imaging should be delayed a minimum of three weeks following therapy to avoid false negatives resulting from therapy suppression of uptake.⁵ It is well known that diffuse lung parenchymal uptake following chemotherapy is a normal response and does not signify active disease (Fig 2).⁶ Less widely recognized phenomena are benign thymic hyperplasia following chemotherapy and the expression of other inflammatory conditions, including sarcoid, mimicking recurrence with radiographic masses, and positive gallium scans.^7,8 Of perhaps greater importance, although thus far reported only in patients with non-Hodgkin’s lymphoma, is the confounding effect of granulocyte colony-stimulating factor (G-CSF), now commonly used to support patients receiving chemotherapy as well as to facilitate stem cell harvest in patients undergoing intensive salvage regimens. Gallium studies in these patients may show diffuse marrow uptake that may obscure a focus of pathologic uptake.⁹

The finding of symmetric abnormal hilar gallium uptake in the absence of abnormalities on chest radiograph or CT has been investigated primarily among patients with non-Hodgkin’s lymphoma.¹⁰ Champion et al¹¹ were able to fully assess 23 such patients and found only five (22%) of these scans to be indicative of viable lymphoma. They note that in 15 of 23 abnormal scans, the hilar uptake was seen only on SPECT images, reflecting the decreased specificity incurred by this technical enhancement.

References

1. Karimjee S, Brada M, Husband J, et al. A comparison of gallium-67 single photon emission computed tomography and computed tomography in mediastinal Hodgkin’s disease. Eur J Cancer. 1992;28A:1856-1857.

2. Front D, Ben-Haim S, Israel O, et al. Lymphoma: predictive value of Ga-67 scintigraphy after treatment. Radiology. 1992;182:359-363.

3. King SC, Reiman RJ, Prosnitz LR. Prognostic importance of restaging gallium scans following induction chemotherapy for advanced Hodgkin’s disease. J Clin Oncol. 1994;12:306-311.

4. Hagemeister FB, Purugganan R, Podoloff DA, et al. The gallium scan predicts relapse in patients with Hodgkin’s disease treated with combined modality therapy. Ann Oncol. 1994;5(suppl 2):59-63.

5. Bekerman C, Hoffer PB, Bitran JD. The role of gallium-67 in the clinical evaluation of cancer. Semin Nucl Med. 1984; 14:296-323.

6. King SC, Reiman RJ, Prosnitz LR. Prognostic importance of restaging gallium scans following induction chemotherapy for advanced Hodgkin’s disease. J Clin Oncol. 1994;12:306-311.

7. Burns DE, Schiffman FJ. Beguiled by the gallium: thymic rebound in an adult after chemotherapy for Hodgkin’s disease. Chest. 1993;104:1916-1919.

8. Bar-Shalom R, Ben-Arie Y, Gaitini D, et al. Gallium-67 uptake in a mass of benign transformation mimicking recurrence of nodular lymphocytic predominance Hodg-kin’s disease. J Nucl Med. 1994;35:465-468.

9. Kondoh H, Murayama S, Kozuka T, et al. Enhancement of hematopoietic uptake by granulocyte colony-stimulating factor in Ga-67 scintigraphy. Clin Nucl Med. 1995;20: 250-253.

10. Larcos G, Farlow DC, Antico VF, et al. The significance of isolated gallium-67 uptake in the hilar lymph nodes of an untreated lymphoma patient. Clin Nucl Med. 1993;18:1039-1041.

11. Champion PE, Groshar D, Hooper HR, et al. Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin’s lymphoma? Nucl Med Commun. 1992;13: 730-737.

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