Anatomical and Functional Imaging 1221 Fdgpet and CT

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

Get Instant Access

Functional imaging with FDG-PET scanning has been found to provide superior diagnostic accuracy compared to anatomical imaging using CT for staging and re-staging lymphoma. In their meta-analysis, Czernin and Phelps [19] showed a markedly improved specificity, which using CT was 39% (95% CI = 30 - 47) compared to 91% (95% CI = 86-96%)

for FDG-PET. Sensitivity of CT alone was 85% (95% CI = 78 -91) and for FDG-PET 93% (95% CI = 89 -98). Moreover, FDG-PET also reflected changes in tumor glucose metabolism associated with chemotherapy and this information was valuable for assessing prognosis.

Assessment of Response to Therapy

Weihrauch et al. [20] showed in their review that post-treatment evaluation of lymphomas with FDG-PET provided positive predictive values ranging from 57 to 100%, and negative predictive values ranging from 67 to 100%. A positive PET scan was more often indicative of progressive disease for NHL than for Hodgkin's lymphoma.

Spaepen et al. [21] report that among 70 patients with newly diagnosed aggressive NHL, a mid-treatment FDG-PET scan provided stronger prognostic information than did the International Prognostic Index. They suggest that an early restaging FDG-PET scan might be used "to tailor induction chemotherapy in patients with aggressive NHL" (p. 1356).

12.2.2 MRI

MRI may be more sensitive than CT for evaluation of abdominal lymph nodes. MRI is also considered superior to CT for the investigation of bone marrow involvement by lymphoma [4, 22]. Pancreatic lymphomas are generally iso-intense to normal pancreas on both Tj and T2 weighted images [23]. Pancreatic adenocarcinomas are also generally difficult to visualize on MRI, making this important distinction difficult, unless vascular encasement of the latter can be delineated (see Chapter 15).

12.2.3 MRS assessment of lymph node involvement and response to therapy

Proton MRS

Schwarz et al. [24] examined 13 patients with extracranial lymphoma or germ cell tumors, including 5 patients with NHL using proton MRS3 immediately before chemotherapy. In order to enter the study, the tumor was required to be at least 3 x 3 cm if superficial, or 5 x 5 cm if deeper lying. The 3.2 ppm resonance was assigned to the trimethyl ammonium N-(CH3)3 moiety of total choline. Signals due to mobile

3 Schwarz, et al. [24], used 1.5T, single voxel, STEAM, TR=2000 ms, TE=20 ms. Follow-up scans attempt to be at the same site as the first. Used MRUI/VARPRO. Gaussian model functions fitted, metabolite signal values expressed as percentages of the water signal at the same TE.

lipids ([CH2])n at 1.3 ppm and CH3 at 0.9 ppm were seen in most spectra; however, many of these tumors were surrounded by fat.

These authors assessed changes in the total choline to water ratio in the first post-treatment scan as a fraction of the pre-treatment ratio in 3 of the 5 patients with NHL shown in Table 12.1, as well as in 6 of the other patients (with Hodgkin's lymphoma or teratomas). Overall, these authors [24] observed in the 9 patients with pre-and post-treatment spectral information, the "changes fell into two clearly distinct patterns that correlated with subsequent clinical response" (p. 962). In 7 patients the total choline to water ratio fell at the post-treatment scan (taken between 5 and 37 days after initiation of therapy). All of these patients were later judged to have a partial response to therapy at 54 to 93 days. In the other 2 patients, the total choline to water ratio remained approximately constant, and both of these patients were considered to have progressive disease.

Importantly, the reduction in total choline to water ratio was observed earlier than volume changes assessed using MRI. The authors of Ref. [24] note that the proton MRS spectra "appeared broadly similar across the different tumor types and histopathology ... {and that} ... any metabolite signals in the 2-2.5 ppm region of the spectrum are likely to be confounded by co-resonant lipid signals"(p. 964). However, the resonances at 3.6 to 4.0 ppm were not assigned.

Table 12.1

Proton MRS Performed in Patients with NHL pre- & post-therapy

Table 12.1

Proton MRS Performed in Patients with NHL pre- & post-therapy

Post/Pre

Diagnosis

Site of Target Lesion

change-total choline: water ratio

Volume from MRI Post/Pre

Clinical Response

Mantle cell

Inguinal Node

0.31

1.02

Partial

Diffuse

Supraclavicular

0

Not

Partial

Large B-cell

Fossa

available

Follicular

Mesentery

0.97

1.16

Progressive Disease

The authors [24] recognize that their patient group is small and heterogeneous, such that larger prospective series with specific pathologies need to be studied. They do note that their findings at 3.2 ppm could be from glycerophosphocholine, phosphocholine and choline, as well as possibly phosphoethanolamine, which has a resonance at about 3.2 ppm on the proton spectrum, as reported in studies using 31P MRS on lymphomas (see next subsection). Nevertheless, their general conclusion is that "based on the differential changes in signal intensities in the {total choline} region of the spectrum following chemotherapy, we hypothesize that metabolic changes observable by 1H MRS may be predictive of subsequent clinical response. In this respect, changes are consistent with those observed in the phosphomonoester region of 31P spectra, which consists primarily of {phosphoethanolamine} PE and {phosphocholine} PC. In combination with other prognostic factors, such as the International Prognostic Index of lymphoma, biochemical information from MRS may find a role in individual patient management" (p. 965).

As discussed in Chapter 3, the advantages of proton MRS include being more easily available on standard MRI equipment, plus the better spatial resolution and sensitivity. In particular, MRS could be helpful for Phase I studies of new therapies against aggressive lymphomas, that target biological end points, but are not expected to dramatically alter tumor size. "The observation of different trends in responders and non-re sponders suggests that further development of this method may provide a sensitive early indicator of metabolic response to treatment" (p. 965) [24].

31P MRS

Most studies of lymphomas have applied 31P MRS. An early investigation by Vogl et al. [25] of 15 patients with superficial masses (lymphomas as well as sarcomas, carcinomas, adenomas and tuberculosis) revealed that tumor growth was associated with increased PME concentrations.

Subsequently, Negendank et al. [26] examined 21 patients with biopsy-proven NHL, 13 of whom were newly diagnosed and previously untreated, and 8 had recurrent disease after therapy. Seven of the patients had low grade, 11 had intermediate and 3 had high histopathologic grade. There were 2 patients with Stage I disease, 4 with Stage II, 6 with stage III and 9 with stage IV disease. Cell types included follicular and diffuse, predominantly; all but 2 of the patients had B-cell lymphomas. These authors applied ^-decoupling and nuclear Overhauser enhancement to improve the resolution of 31P MRS localized to lymphoma-containing lymph nodes or masses within 10 cm of the body surface. All the MR spectra showed large PME signals (26% of total phosphorus) with a high phosphoethanolamine to phosphocholine ratio. Glycerophosphoethanolamine and glycerophosphocholine were not detected, but there was a broad signal from membrane phospholipids in the phosphodiester region, comprising about 20% of the phosphorus. The nucleotide triphosphate (NTP) was prominent and inorganic phosphate was low, suggesting that the tissues were well perfused and that the cells were viable. These findings were similar in all grades and stages of NHL. The authors [26] interpreted these findings in light of in vitro studies, which differed from the present ones. They suggest: "the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D" (p. 3286).

More recently, Griffiths et al. [27] in a multi-center study evaluated changes in PME/NTP ratios in relation to response to treatment in superficial lymph nodes of patients with NHL. There was a clear relation between change in this ratio and level of response: The 14 complete responders showed a highly significant fall in the PME/NTP ratio from 1.47 ± 0.11 to 0.47 ± 0.11, after therapy (p < 0.001), the 13 partial responders had a smaller, but still significant fall (p < 0.05) from 1.88 ± 0.15 to 1.30 ± 0.22, while the 16 patients who did not respond to therapy had a non-significant rise in PME/NTP ratio. Their results are graphically displayed in Figure 12.1.

Figure 12.1: Pre- and Post Treatment PME/NTP ratios (superficial lymph node) & Clinical response in 43 Patients with Non-Hodgkin's Lymphoma (From data of Griffiths et al. [27])

Complete Responders Partial Responders

Complete Responders Partial Responders

Non-Responders

12.2.4 31P-MRS assessment of hepatic lymphoma

Heindel et al. [28] compared the in vivo 31P MR spectra from liver of 13 patients with suspected hepatic involvement from Hodgkin's lymphoma, with those from 22 healthy volunteers. Their findings were:

• Increased phosphomonoester to P-NTP ratio in all the patients compared to the referents,

• Higher phosphomonoester to P-NTP ratios and lower pH in patients with liver infiltration than those patients without hepatic involvement,

• Increased inorganic phosphate to P-NTP ratios after therapy compared to prior to treatment with cytostatics, as examined in 3 patients.

The authors [28] conclude that 31P-MRS can provide insights concerning hepatic involvement in patients with lymphoma, which are rarely gleaned from other imaging modalities.

Dixon [29] reported that of 11 patients with Hodgkin's and non-Hodgkin's lymphoma involving the liver, six showed elevated PME/Pi ratios on 31P MRS of the liver. In two of these patients this ratio dropped to within the normal range with clinical remission, whereas four patients in whom this ratio remained high after chemotherapy died of progressive disease.

12.2.5 31P-MRS assessment of testicular lymphoma

Kiricuta et al. [30] presented a case report of a patient with testicular involvement from recurrent NHL, treated with mega voltage RT. Prior to therapy the 31P MR spectrum showed large phosphomonoester and phosphodiester peaks that overlapped the inorganic phosphate peak. After about half the RT administration the inorganic phosphate peak appeared and the pH lowered to 7.08 (close to normal in the testis of 7.02). After completion of RT the tumor disappeared and the patient went into complete remission. The authors suggest that inorganic phosphate and phosphomonoester might be used as markers of the response to RT.

References

[1] J. Coffey, D.C. Hodgson, M.K. Gospodarowicz, Therapy of non-Hodgkin's lymphoma, Eur. J. Nucl. Med. Molecular Imaging 30 (Suppl. 1), S28-S36 (2003).

[2] M. Melbye, D. Trichopoulos, Non-Hodgkin's lymphoma, in: H-O. Adami, D. Hunter, D. Trichopoulos, Textbook of Cancer Epidemiology, Oxford University Press, Oxford, 2002, p. 535555.

[3] J.O. Armitage, D.L. Longo, Malignancies of lymphoid cells, in: E Braunwald, A. Fauci, D.L. Kasper, S.L. Hauser, D.L. Longo, J.L. Jameson, Harrison's Principles of Internal Medicine, 15th Edition, McGraw-Hill, New York, 2001, p. 715-727.

[4] J. O. Armitage, P.M. Mauch, N.L. Harris, P. Bierman, Non-Hodgkin's lymphomas, in: V.T. de Vita, S. Hellman, S.A. Rosenberg, Cancer Principles & Practice of Oncology 6th Edition, Lippincott Williams & Wilkins, Philadelphia, 2001, p. 2256-2316.

[5] B. Alpen, J. Robbecke, T. Wundisch, M. Stolte, A. Neubauer, Helicobacter pylori eradication therapy in gastric high-grade non-Hodgkin's lymphoma, Ann. Hematol. 80 (Suppl. 3), B106-B107 (2001).

[6] J.A. Bukowski, W.W. Huebner, A.R. Schnatter, N.C. Wojcik, An analysis of the risk of B-lymphocyte malignancies in industrial cohorts, J. Toxicol. Environ. Health A 66, 581-597 (2003).

[7] E. Lee, C.A. Burnett, N. Lalich, L.L. Cameron, J.P. Sestito, Proportionate mortality of crop and livestock farmers in the United States, 1984-1993, Am. J. Indust. Med. 42, 410-420 (2002).

[8] J. Simpson, E. Roman, G. Law, B. Pannett, Women's occupations and cancer: preliminary analysis of cancer registrations in England and Wales, 1971-1990, Am. J. Indust. Med. 36, 172-185 (1999).

[9] T. Zheng, A. Blair, Y. Zhang, D.D. Weisenburger, S.H. Zahm, Occupation and risk of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, J. Occup. Environ. Med. 44, 469-474 (2002).

[10] M.I. Cano, M. Pollan, Non-Hodgkin's lymphomas and occupation in Sweden, Int. Arch. Occup. Environ. Health 74, 443-449 (2001).

[11] J.C. Schroeder, A.F. Olshan, R. Baric, et al., Agricultural risk factors for t (14; 18) subtypes of non-Hodgkin's lymphoma, Epidemiology. 12, 701-709 (2001).

[12] S. Roulland, P. Lebailly, Y. Lecluse, M. Briand, D. Pottier, P. Gauduchon, Characterization of the t (14; 18) BCL2-IGH translocation in farmers occupationally exposed to pesticides, Cancer Res. 64, 2264-2269 (2004).

[13] A.S. Costantini, L. Miligi, D. Kriebel, et al., A multi-center case-control study in Italy on hematolymphopoietic neoplasms and occupation, Epidemiology 12, 78-87 (2001).

[14] Y. Mao, J. Hu, A.M. Ugnat, K. White, Non-Hodgkin's lymphoma and occupational exposure to chemicals in Canada, Ann. Oncol. 11 (Suppl. 1), 69-73 (2000).

[15] L. Varoczy, L. Gergely, M. Zeher, G. Szegedi, A. Illes, Malignant lymphoma-associated autoimmune diseases—a descriptive epidemiological study, Rhematol. Int. 22, 233-237 (2002).

[16] D.J. van Spronsen, M.L. Janssen-Heijnen, W.P. Breed, J.W. Coebergh, Prevalence of co-morbidity and its relationship to treatment among unselected patients with Hodgkin's disease and non-Hodgkin's lymphoma, Ann. Hematol. 78, 315-319 (1999).

[17] K. Belkic, P.L. Schnall, C. Savic, P.A. Landsbergis, Multiple exposures: Towards a model of total occupational burden, in: P.L. Schnall, K. Belkic, P.A. Landsbergis, Baker D (eds.)

Occupational Medicine: State of the Art Review. The Workplace and Cardiovascular Disease. 15, 94-105 (2000).

[18] M.L.V. Fasan, E. Morandi, P. Fociani, et al., AIDS-associated gastrointestinal lymphoma: Is there a role for surgery in the standard of care? J. Acquir. Immune Defic. Syndr. 34, 345-347

[19] J. Czernin, M.E. Phelps, Positron emission tomography scanning: Current and future applications, Annu. Rev. Med. 53, 89-112 (2002).

[20] M.R. Weihrauch, M. Dietlein, H. Schicha, V. Diehl, H. Tesch, Prognostic significance of 18F-flurodeoxyglucose positron emission tomography in lymphoma, Leukemia Lymphoma, 44, 15-22 (2003).

[21] K. Spaepen, S. Stroobants, P. Dupont, et al., Early restaging positron emission tomography with (18) F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma, Ann. Oncol. 13, 1356-1363 (2002).

[22] V. Diehl, P.M. Mauch, N.L. Harris, Hodgkin's disease, in: V.T. de Vita, S. Hellman, S.A. Rosenberg, Cancer Principles & Practice of Oncology 6 Edition, Lippincott Williams & Wilkins, Philadelphia, 2001, p.2339-2387.

[23] M.K. Kalra, M.M. Maher, P.R. Mueller, S. Saini, State-of-the-art imaging of pancreatic neoplasms, Br. J. Radiol. 76, 857-865 (2003).

[24] A.J. Schwarz, N.R. Maisey, D.J. Collins, D. Cunningham, R. Huddart, M.O. Leach, Early in vivo detection of metabolic response: a pilots study of 1H MR spectroscopy in extracranial lymphoma and germ cell tumors, Br. J. Radiol. 75, 959-966 (2002).

[25] T. Vogl, F. Peer, H. Schedel, et al., 31P-spectroscopy of head and neck tumors—surface coil technique, Magn. Reson. Imaging 7, 425-435 (1989).

[26] W. G. Negendank, K.A. Padavic-Shaller, C-W. Li, et al., Metabolic characterization of non-Hodgkin's lymphomas in vivo with proton-decoupled phosphorus MRS, Cancer Res. 55, 32863294 (1995).

[27] J.R. Griffiths, A.R. Tate, F.A. Howe, M. Stubbs, as part of the Multi-Institutional Group on MRS Application to Cancer, Magnetic resonance spectroscopy of cancer - practicalities of multi-centre trials and early results in non-Hodgkin's lymphoma, Eur. J. Cancer 38, 2085-2093 (2002).

[28] W. Heindel, R. du Mesnil de Rochemont, H. Kugel, et al. 31P-MR spectroscopy of the human liver—the spectral indications of lymphoma infiltration, ROFO-Frotschritte 167, 62-70 (1997).

[29] R.M. Dixon, NMR studies of phospholipid metabolism in hepatic lymphoma, NMR Biomed. 11, 370-379 (1998).

[30] I. C. Kiricuta, R.G. Bluemm, J. Ruhl, H.K. Bever, 31P-MR spectroscopy and MRI of a testicular non-Hodgkin lymphoma recurrence to monitor response to irradiation. A case report,

Strahlenth. Onkol. 170, 359-364 (1994).

Was this article helpful?

0 0
Boost Your Metabolism and Burn Fat

Boost Your Metabolism and Burn Fat

Metabolism. There isn’t perhaps a more frequently used word in the weight loss (and weight gain) vocabulary than this. Indeed, it’s not uncommon to overhear people talking about their struggles or triumphs over the holiday bulge or love handles in terms of whether their metabolism is working, or not.

Get My Free Ebook


Post a comment