Michael V. Williams

Long-term cardiovascular risk following platinum-based chemotherapy for germ cell tumors

Background Germ cell tumors (GCTs) are one of the most curable of the solid neoplasms. They are highly sensitive to platinum-based chemotherapy, which contributes to 5 - year survival rates exceeding 90%. Any late effects of treatment are a key consideration when treating a highly curable disease in a young population. There is good evidence that platinum-based chemotherapy increases the risk of cardiovascular morbidity and mortality late in life; the exact nature of the risk is not well understood, nor is there any consensus on a mechanism for this effect. This article examines the current literature to assess the nature and size of the risk posed, and considers possible mechanisms for the effect. We consider the implications of treatment for GCT with platinum-based chemotherapy, as well as the implications for long-term follow-up and optimal clinical care of patients requiring systemic therapy. Discussion

Stage migration and pilot studies of reduced chemotherapy supported by positron-emission tomography findings suggest new combined strategies for stage 2 nonseminoma germ cell tumour

To examine the nodal (N+) vs extranodal (M+) staging in each of the International Germ Cell Consensus Classification Group (IGCCCG) subgroups in an audit of 437 patients treated in The Anglian Germ Cell Cancer Group, where chemotherapy was the primary management, as there is an increasingly earlier presentation of patients with less advanced disease who thus face potentially unnecessary treatment.

Urologic oncology: Poor trial accrual hinders germ cell tumor therapy advances

In the last 3 years, three major trials involving patients with advanced germ cell testicular tumors have investigated dose-intense alternatives to standard BEP (bleomycin, etoposide, and cisplatin) therapy. All three trials failed to reach their accrual targets and none was able to demonstrate improved results.

Favourable IGCCCG subgroups of stage II NSGCT patients may require less chemotherapy if TNM staging is included

4532 Background: When the IGCCCG prognostic factor analysis was performed there were few stage II cases included in this analysis of chemotherapy cases. Patients were not included from centres which used primary retroperitoneal lymph node dissection followed either by 2 courses of adjuvant chemotherapy or 3 courses at relapse. Primary surgery is the standard of care in North America but not in Europe where primary chemotherapy is used. To investigate this issue the impact of nodal (stage II) versus extra nodal (stage IV) metastases in each of the IGCCCG sub-groups has been examined in an audit of 447 patients treated in centres where chemotherapy rather than RPLND was primary management for stage 2 non-seminoma. METHODS Clinicians from 7 centres (St Barts, Oldchurch, Southend, Colchester, Ipswich, Norwich and Cambridge) have prospectively registered cases in a central data base at St Barts and notes review and follow up has been co-ordinated. RESULTS Between 1982 and 2002 447 patients were registered and survival analysis performed. Stage II cases comprised 63% of IGCCCG good-risk group (N=298), 42% of intermediate and 10% of poor risk patients. With median FU of 60 months there was no significant difference in survival for good-risk patients 92% of stage II (i.e. N+, n=156); 85% of stage IV (i.e. M+, n=94). In contrast survival was significantly influenced in intermediate and poor risk cases with 79% of stage II (N+, n=29) patients alive compared to 60% of stage IV (M+, n=92) (x2 4.05p = <0.05). There was no difference in survival between patients having 3 or 4 courses of treatment and no relapses in 8 who stopped treatment after two courses because of extenuating circumstances. CONCLUSIONS Extralymphatic spread (stage IV) is prognostically significant within intermediate and poor risk IGCCCG. This influence is not seen in good risk patients and the observation that there may be N+ patients in whom it is possible to reduce treatment to 2 courses should be explored further. No significant financial relationships to disclose.