Pathology and genetics of tumors of soft tissue and bone

The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group

The introduction of an effective blood test, prostate specific antigen (PSA), has made it possible to diagnose more and more men in an earlier stage where they can be offered potentially curative treatments. The other side of the coin is that if effective diagnostic procedures are used unselectively in elderly men with a short life expectancy, a problem with over diagnosis and over treatment might occur. Thus the same stage of prostate cancer may need different treatment strategies, pending on the patient’s life expectancy. This, and many other issues regarding the disease, is the subject of the EAU guidelines on prostate cancer. G UI DE LI N ES O N P RO ST AT E CA N CE R 10

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Guidelines on Prostate Cancer

PURPOSE: To determine the effect of radiotherapy dose on prostate cancer patient outcome and biopsy positivity in a phase III trial. PATIENTS AND METHODS: A total of 305 stage T1 through T3 patients were randomized to receive 70 Gy or 78 Gy of external-beam radiotherapy between 1993 and 1998. Of these, 301 were assessable; stratification was based on pretreatment prostate-specific antigen level (PSA). Dose was prescribed to the isocenter at 2 Gy per fraction. All patients underwent planning pelvic computed tomography scan to confirm prostate position. Treatment failure was defined as an increasing PSA on three consecutive follow-up visits or the initiation of salvage treatment. Median follow-up was 40 months. RESULTS: One hundred fifty patients were randomized to the 70-Gy arm and 151 to the 78-Gy arm. The difference in freedom from biochemical and/or disease failure (FFF) rates of 69% and 79% for the 70-Gy and 78-Gy groups, respectively, at 5 years was marginally significant (log-rank P = .058). Multiple...

Preliminary Results of a Randomized Radiotherapy Dose-Escalation Study Comparing 70 Gy With 78 Gy for Prostate Cancer

Most patients with plasma cell neoplasia have generalized disease at diagnosis, i.e. multiple myeloma (MM). However, a minority (<5%) of patients with plasma cell malignancies present with either a single bone lesion, or less commonly, a soft tissue mass, of monoclonal plasma cells: solitary bone plasmacytoma (SBP) or extramedullary plasmacytoma (SEP). SBP has a high risk of progression to MM and on magnetic resonance imaging (MRI) examination at least 25% of patients with an apparent solitary lesion have evidence of disease elsewhere (Moulopoulos et al, 1993). In contrast, SEP is nearly always truly localized and has a high cure rate with local treatment. The diagnosis and management of patients with solitary plasmacytoma requires the same range of clinical and laboratory expertise as for patients with MM (UK Myeloma Forum, 2001). The primary treatment for most patients will be radiotherapy, but surgery may also be required, where close liaison among the haematologist, radiotherapist and surgeon is crucial for planning optimum care. Methods A literature search was performed by a professional librarian using MEDLINE and EMBASE from 1996 to March 2002. A search was made for randomized-controlled trials involving plasmacytoma, papers where plasmacytoma was the major focus of the paper and reviews where plasmacytoma was the major focus. The literature was then reviewed by the subgroup of the Guidelines Working Group of the UK Myeloma Forum. Levels of evidence and grades of recommendation are shown in Table I. SBP and SEP are rare diseases and most of the evidence relates to retrospective data from patient series collected over long periods of time. Very few formal clinical trials have been performed. The majority of the recommendations given are therefore based on consensus of expert

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Guidelines on the diagnosis and management of solitary plasmacytoma of bone and solitary extramedullary plasmacytoma.

Purpose: To clarify the natural history of solitary plasmacytoma of bone (SBP) after radiation treatment. Methods and Materials: Between 1965–1996, we identified 57 previously untreated patients with a SBP. A serum myeloma protein was present in 33 patients (58%) and Bence Jones proteinuria was present in an additional eight patients (14%). The median radiotherapy dose was 50 Gy (range, 30–70 Gy). Overall survival, cause-specific survival, and freedom from progression to multiple myeloma were calculated actuarially. Results: Local control was achieved in 55 of 57 patients (96%). For those 29 patients (51%) who subsequently developed multiple myeloma, the median time to progression was 1.8 years. There was a direct correlation between persistence of abnormal protein following radiotherapy and the likelihood of developing multiple myeloma. Among 11 patients with disappearance of myeloma protein, only two developed multiple myeloma after 4 and 12 years, in contrast to progression in 57% of patients with a persistent protein peak and 63% of those with nonsecretory disease ( p = 0.02). Among 23 patients with thoracolumbar spine disease, 7 of 8 patients staged with plain radiographs alone developed multiple myeloma in comparison with 1 of 7 patients who also had magnetic resonance imaging (MRI) ( p = 0.08). For all patients, the median survival from radiotherapy was 11.0 years. The median cause-specific survival of patients with disappearance of myeloma protein was significantly longer than that of the remaining patients ( p = 0.004). Conclusion: Results supported the importance of precise staging that includes MRI of the spine for optimum patient selection and the application of definitive radiotherapy. Those patients with myeloma protein that disappears following radiotherapy represent a category with a high likelihood of cure.

Solitary bone plasmacytoma: outcome and prognostic factors following radiotherapy

BACKGROUND

Despite its subjectivity and inaccuracy, digital rectal examination (DRE) has a long history of well-documented prognostic significance in patients with prostate carcinoma. To the authors' knowledge, very few studies have evaluated the relative prognostic merits of transrectal ultrasound (TRUS) versus DRE. This question is addressed in this study.



METHODS

The outcome for 558 men with T1–T3, N0, M0 adenocarcinoma of the prostate who underwent both DRE and TRUS and received external beam radiation without androgen ablation was evaluated relative to the prognostic information from DRE, TRUS, or both. The outcome endpoints were no evidence of disease (NED) (no relapse or rising prostate specific antigen level) and freedom from metastases. Prognostic factors were evaluated with univariate and multivariate techniques. The median follow-up was 55 months.



RESULTS

Both purely DRE-based and purely TRUS-based T categories correlated significantly with NED status. For DRE T categories, 6-year NED rates for T1/T2 and T3 disease were 64% and 36%, respectively (P < 0.001). For TRUS T categories, the rates for T1/T2 and T3 were 63% and 39%, respectively (P < 0.001). There were significant differences in patient composition between DRE and TRUS T categories. Only 40% of patients were in the same DRE and TRUS category, but the majority of the reclassification based on TRUS was within rather than between major T categories (T1/T2 vs. T3). Changes between the prognostically significant T1/T2 versus T3 categories occurred in ≤25%. This accounted for the similarity in NED outcome for DRE and TRUS T categories. However, TRUS categories did not discriminate significantly for metastatic recurrence between T1/T2 and T3 categories, whereas DRE categories did. Upstaging or downstaging by TRUS relative to DRE did not alter the DRE prognostic groupings substantially.



CONCLUSIONS

There was no clinically meaningful superiority of TRUS over DRE in the definition of prognostically useful T categories. Moreover, the addition of TRUS to DRE did not enhance the prognostic value of DRE findings in any meaningful way. Despite its subjectivity and inaccuracy, DRE provides prognostic information at least equivalent to TRUS and is preferable because of its low cost. Cancer 1999;85:1577–85. © 1999 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0142%2819990401%2985%3A7%3C1577%3A%3AAID-CNCR20%3E3.0.CO%3B2-G

Robert H. Liebross

Papers

Solitary bone plasmacytoma: outcome and prognostic factors following radiotherapy

Transrectal ultrasound for staging prostate carcinoma prior to radiation therapy: an evaluation based on disease outcome.

Relationship of ultrasound staging and bilateral biopsy positivity to outcome in stage T1c prostate cancer treated with radiotherapy

50 Mucosal melanoma of the head and neck