Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.

BACKGROUND: Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome. METHODS: Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done. RESULTS: A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. CONCLUSIONS: Using Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with Seminoma stage I and should not be regarded as standard of care.

Experience of first- and subsequent-line systemic therapy in the treatment of non-small cell lung cancer.

INTRODUCTION: The treatment of advanced non-small cell cancer (NSCLC) has changed with multiple new treatment algorithms proposed based on histological and molecular subtyping but low mutation rates will ensure the dominance of cytotoxic chemotherapy. Accordingly, we undertook a detailed review of our practice delivering multiple lines of systemic therapy. METHOD: We undertook a retrospective review of consecutive patients presenting with advanced (stage IIIb/IV) NSCLC treated with systemic therapy at two UK hospitals during a 2-year period, January 2007 to December 2008. RESULTS: A total of 130 patients were identified, treated with predominantly carboplatin/gemcitabine (20 initially radically). Fifty of 110 patients (45%) treated with first-line systemic therapy subsequently received second-line therapy, of which 10 patients received third-line and two patients fourth-line therapy. Sixty three of 110 first-line patients (58%) achieved clinical benefit, 19 out of 50 (38%) in the second-line, 6 out of 10 (60%) in third-line but both patients progressed at fourth-line. Median overall survival for 110 patients was 10 months (95% confidence interval [CI] 8.6-11.4); but 16 months (95% CI 14-17.9) in those receiving multiple lines. Median survival from the first cycle of last-line treatment to death in the multiple therapy lines was 5 months (95% CI 2.6-7.3) and the majority of patients spent more time off treatment. CONCLUSION: Overall our outcomes are consistent with published data and show good survival times can be achieved. The future of advanced NSCLC is in selecting the best treatment approach on a histological and genotypic basis.

Late relapse of metastatic non-seminomatous testicular germ cell tumours.

Although the majority of men presenting with non-seminomatous germ cell tumours (NSGCT) are cured, late relapse (occurring more than 2 years after obtaining a complete response to treatment) is increasingly recognized. The typical patterns of disease spread have been well-documented, but the findings at late relapse are more variable and less well-described. We discuss the phenomenon of late relapse, the characteristics of teratoma differentiated (TD), and the issue of long-term imaging surveillance of patients with NSGCT. The potential sites of late relapse of NSGCT and the associated spectrum of imaging appearances are illustrated.

An unusual differential diagnosis of penile warts: metastases from rectal carcinoma.

Patients with penile lesions, such as virally induced papillomata, frequently present to genitourinary medicine clinics and general practitioners. Their diagnosis is usually based on clinical observation and biopsy is not generally undertaken. Penile lesions may rarely have a more sinister aetiology and represent metastatic spread from solid tumours arising at distant sites. Penile metastases arise most frequently from genitourinary cancers (prostate, bladder and kidney), but may also arise from tumours of the large bowel; other primary sites are extremely uncommon. We report the case of a patient presenting with penile metastases from rectal carcinoma arising during third-line chemotherapy for metastatic disease.

Orchidectomy after chemotherapy for patients with metastatic testicular germ cell cancer.

OBJECTIVE: To evaluate the contribution of routine orchidectomy in the management of patients who present with advanced, metastatic, testicular germ cell cancer and who are treated with initial chemotherapy. PATIENTS AND METHODS: Sixty consecutive patients presenting with metastatic testicular germ cell cancer and treated with initial chemotherapy followed by orchidectomy were identified. The results from a clinical and pathological review of these patients are presented. The pathological findings at orchidectomy were compared with the pathological findings from metastatic masses resected after chemotherapy, and are reviewed with the clinical outcome. RESULTS: Of the 60 orchidectomy specimens after chemotherapy, 24 (40%) contained significant histological abnormalities comprising residual invasive germ cell cancer, intratubular germ cell neoplasia and/or mature teratoma. The remaining 36 (60%) orchidectomy specimens contained fibrous scarring with or with no necrosis. Six (10%) orchidectomy specimens contained residual invasive germ cell cancer, three nonseminomatous germ cell cancer (NSGCT) and three seminoma. The patients with residual invasive NSGCT present within the testis had evidence of residual invasive NSGCT within extragonadal masses resected after chemotherapy; all three have relapsed and died from chemorefractory progressive disease. CONCLUSION: Orchidectomy after chemotherapy is recommended in all patients undergoing primary chemotherapy, as a significant proportion (40%) are left with histological abnormalities that predispose to subsequent relapse. Persistence of invasive NSGCT at the site of the primary tumour after chemotherapy is associated with persistence of invasive disease at other metastatic sites and is a poor prognostic finding.

Routine computerised tomographic scans of the thorax in surveillance of stage I testicular non-seminomatous germ-cell cancer--a necessary risk?

BACKGROUND: The standard management approach to stage I testicular non-seminomatous germ-cell tumours (NSGCT) in the UK is a surveillance programme with adjuvant bleomycin, etoposide, cisplatin (BEP) chemotherapy being offered to individuals with high risk disease. Conventionally, computed tomography (CT) scanning of the thorax has formed part of the surveillance programme. This paper evaluates the contribution of routine thoracic CT imaging in the management of this disease. PATIENTS AND METHODS: We retrospectively reviewed the case notes of 168 patients with stage I NSGCT referred to the Wessex Medical Oncology Unit over a period of 13 years (1986-1998). These patients entered onto a surveillance programme that included serial chest X-ray follow up rather than thoracic CT. RESULTS: Forty-two out of 168 patients (25%) evaluated suffered relapse during the follow up period. Eight of 42 patients (19%) relapsed with intrathoracic disease. Seven out of eight of these patients (87.5%) had at least one other indicator of disease recurrence (elevated serum marker, abnormal abdominal CT). One of 42 patients (2.4%) relapsed with isolated intrathoracic disease with no other indicator of relapse. All patients with intrathoracic relapse had evidence of disease on chest X-ray. Of the 42 relapsing patients, 93% could be categorised as having good prognosis metastatic disease. Seven per cent relapsed with intermediate or poor prognostic disease; relapse in these patients would not have been detected earlier with the inclusion of routine thoracic CT. Only one patient has died giving a cure rate of 98% for relapsing patients. CONCLUSIONS: The elimination of chest CT did not compromise outcome but significantly reduced radiation exposure thereby minimising the risk of radiation-induced secondary malignancy. Continued review of surveillance programmes is essential if we are to optimise management of this disease.