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.

Sex cord stromal testicular tumors: a clinical series--uniformly stage I disease.

PURPOSE: Sex cord stromal testicular tumors are rare. Historically 10% of lesions are said to be malignant but to our knowledge there are no clinical or histological features that can accurately predict potential malignant behavior. Because of this, groups at some centers have advocated prophylactic retroperitoneal lymph node dissection in patients with clinical stage I disease. We reviewed our experience with these tumors to determine whether this policy is justified. MATERIALS AND METHODS: We retrospectively reviewed the records of all 38 men older than 18 years with sex cord stromal testicular tumors who were referred to the Wessex regional cancer center for treatment or pathological review during the 25-year period of 1982 to 2006. We then compared our series with a malignant sex cord stromal testicular tumor database generated from the world literature. RESULTS: All Wessex patients were treated with excision of the primary tumor alone and metastatic disease developed in none. All remained disease-free with an overall median survival of 6.8 years (range 1.4 to 25). Features in the literature favoring malignant behavior, ie metastatic disease, included larger tumors (mean 6.43 vs 1.71 cm), a high mitotic rate, tumor necrosis, angiolymphatic invasion, infiltrative margins and extratesticular extension (each p <0.0001). The malignant group had an overall median survival of 2.3 years (range 0.02 to 17.3). CONCLUSIONS: No patient had disease progression in our study, which is to our knowledge the largest reported United Kingdom series of sex cord stromal testicular tumors. Our data suggest that malignancy is uncommon and prophylactic retroperitoneal lymph node dissection is unjustified for clinical stage I disease.

Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial.

BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7x[glomerular filtration rate+25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0-4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3-97.7] vs 97.7% [96.0-98.6] at 2 years; 95.9% [94.4-97.1] vs 94.8% [92.5-96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85-1.93], p=0.32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0-3.8] vs 0.54% [0.1-2.1], p=0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. INTERPRETATION: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.

Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party.

BACKGROUND: Because metastatic nonseminomatous germ cell cancer is a rare but treatable cancer, we have explored whether there is an association between the experience of the treating institution with this disease and the long-term clinical outcome of the patients, particularly patients with a poor prognosis. METHODS: We analyzed data on 380 patients treated in one of 49 institutions participating in the European Organization for Research and Treatment of Cancer/ Medical Research Council randomized trial of four cycles of bleomycin-etoposide-cisplatin followed by two cycles of etoposide-cisplatin versus three cycles of bleomycin-vincristine-cisplatin followed by three cycles of etoposide-ifosfamide-cisplatin-bleomycin, both treatment regimens given with or without filgrastim (granulocyte colony-stimulating factor). Institutions were divided into four groups based on the total number of patients entered in the trial. The groups were compared by use of the Cox proportional hazards model stratified for treatment with filgrastim and for patient prognosis as defined by the International Germ Cell Consensus Classification Group. With the use of this classification, only 65 % of the patients had a poor prognosis. RESULTS: Patients treated in the 26 institutions that entered fewer than five patients into the trial had an overall survival that was statistically significantly worse (two-sided P = .010; hazard ratio = 1.85; 95% confidence interval = 1.16-3.03) than that of patients treated in the 23 institutions that entered five patients or more. Overall survival and failure-free survival were similar among institutions that entered at least five patients. The observed effect may be related to differences in adherence to the chemotherapy protocol and in the frequency and extent of surgery for residual masses, although only the differences in dose intensity achieved statistical significance. CONCLUSIONS: Patients treated in institutions that entered fewer than five patients into the trial appeared to have poorer survival than those treated in institutions that entered a larger number of patients with "poor-prognosis" nonseminoma.

Case series: adult testicular dermoid tumours--mature teratoma or pre-pubertal teratoma?

Adult testicular dermoid tumours are rare tumours with no reported potential for recurrent or metastatic spread. Despite this they are currently classified as mature teratoma and managed as if they have equivalent malignant potential. This report describes two cases of adult mature teratoma of dermoid type and questions the classification and pathogenesis of this disease. In one of the cases there was a clear history of a testicular lump arising pre-pubertally, raising the possibility that some adult dermoid tumours may in fact be pre-pubertal teratomas that have persisted into adulthood. Classification as a mature teratoma carries with it a follow-up regimen that includes numerous radiological investigations with their attendant radiation exposure. A positive histological diagnosis and separate classification of adult dermoid tumours would allay clinical fears of recurrence and metastasis and negate the need for repeated radiological investigations.

Intensive weekly combination chemotherapy for patients with intermediate-grade and high-grade non-Hodgkin's lymphoma.

High response and overall survival rates have been reported for second- and third-generation combination chemotherapy regimens used in the treatment of advanced intermediate- and high-grade non-Hodgkin's lymphoma (NHL). Results with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy have been particularly impressive, although this regimen produces considerable toxicity. We have devised a similar regimen, which differs from previously reported weekly regimens in that it includes etoposide given at 14-day intervals. The doses of methotrexate and prednisolone were lower in our regimen than those used in MACOP-B. Alternating cycles of cyclophosphamide, doxorubicin, and etoposide (week 1) and methotrexate, bleomycin, and vincristine (week 2) were given for a total of 12 weeks, with continuous oral prednisolone and prophylactic antibiotics. We report here the first 61 patients entered onto this study. The overall response rate is 84% (57% complete remission [CR], 27% partial remission [PR]). With a median follow-up of 32 months for surviving patients, the actuarial overall survival at 3 years is 47%, and the failure-free survival is 45%. The dose-limiting toxicity of this regimen was mucositis. Five deaths occurred during chemotherapy, two of which were due to sepsis. The dose intensities of cyclophosphamide and doxorubicin in this regimen are considerably lower than those in MACOP-B. However, because of the inclusion of etoposide, the projected average relative dose intensity for our regimen is higher than that for MACOP-B. Our regimen has produced inferior results to those reported for MACOP-B. This may be because the addition of etoposide has failed to compensate for the lower doses of doxorubicin and cyclophosphamide. Alternatively, it may reflect differences in the presenting features of the patient populations.

Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center.

PURPOSE: We report the clinical features and treatment of 31 patients with a diagnosis of enteropathy-type intestinal T-cell lymphoma treated at the Wessex Regional Medical Oncology Unit in Southampton between 1979 and 1996 (23 men, eight women). PATIENTS AND METHODS: Patients were identified from our lymphoma database. Details of history, physical examination, staging investigations, treatment, and outcome were taken from patient records. RESULTS: Twelve patients (35%) had a documented clinical history of adult-onset celiac disease, and a further three had histologic features consistent with celiac disease in resected areas of the small bowel not infiltrated with lymphoma. After diagnosis, 24 (77%) of the 31 patients were treated with chemotherapy; the remaining seven had surgical treatment alone. More than half were unable to complete their planned chemotherapy courses, often because of poor nutritional status; 12 patients required enteral or parenteral feeding. A response to initial chemotherapy was observed in 14 patients (complete response, n = 10; partial response, n = 4). Observed complications of treatment were gastrointestinal bleeding, small-bowel perforation, and the development of enterocolic fistulae. Relapses occurred 1 to 60 months from diagnosis in 79% of those who responded to initial therapy. Of the total 31 patients, 26 (84%) have died, all from progressive disease or from complications of the disease and/or its treatment. The actuarial 1- and 5-year survival rates are 38.7% and 19.7%, respectively, with 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively. CONCLUSION: The prognosis for these patients is poor. This, in part, reflects late diagnosis and poor performance status at the time of presentation. The role of salvage treatments and high-dose chemotherapy at relapse is not clear. However, it is encouraging that there are five long-term survivors in our patient population.

The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party.

PURPOSE: To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS: Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS: With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS: The first four factors were used to define a simple prognostic classification. A good-prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials.

Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial.

A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.

Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council.

PURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles. RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.

Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study.

PURPOSE: The aim of this randomized trial was to assess the potential therapeutic advantage of an intensive induction-sequential chemotherapy schedule (bleomycin, vincristine, cisplatin [BOP])/etoposide, ifosfamide, cisplatin, and bleomycin [VIP-B]), compared with a regimen based on bleomycin, etoposide, and cisplatin (BEP) (BEP/etoposide and cisplatin [EP]) for the treatment of patients with poor-prognosis metastatic nonseminomatous germ cell tumors (NSGCTs). PATIENTS AND METHODS: Patients had one or more of the following: a retroperitoneal mass > or = 10 cm in diameter; mediastinal or supraclavicular mass > or = 5 cm in diameter; at least 20 lung metastases (any size); liver, bone, or brain metastases; and serum beta human chorionic gonadotropin (betaHCG) > or = 10,000 IU/L or alfa fetoprotein (AFP) > or = 1,000 IU/L. A total of 380 patients were accrued between May 1990 and June 1994 into this joint Medical Research Council (MRC)/European Organization for Research and Treatment of Cancer (EORTC) trial; of these, nine patients were deemed ineligible. RESULTS: There was no significant difference between the two arms in the proportion of patients who achieved a complete response (CR) with chemotherapy alone, ie, 79 of 185 assessable patients (57%) with BEP/EP and 72 of 186 (54%) with BOP/VIP-B (P = 0.687). With a median follow-up of 3.1 years (maximum, 5.8), a total of 107 patients (28%) had progressive disease. There was no significant difference in time to first disease progression, or failure-free or overall survival between the two arms (P = 0.21, 0.101, and 0.190, respectively). The 1-year failure-free survival rates for BEP/EP and BOP/VIP-B were 60% (95% confidence interval [CI], 53% to 67%) and 53% (95% CI, 47% to 61%). Grade 3 or 4 myelosuppression, febrile neutropenia, and weight loss were more pronounced with BOP/VIP-B than with BEP/EP, and there were more toxic deaths with BOP/VIP-B than BEP/EP (18 [9%] v nine [5%]). CONCLUSION: The intensive BOP/VIP-B therapy was associated with more toxicity, but there was no evidence of an improvement in response rate or survival compared with treatment with BEP/EP.

Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom.

PURPOSE: To determine the effect of r-metHu granulocyte colony-stimulating factor (G-CSF) on the proportion of patients with metastatic poor-prognosis malignant germ cell tumors who receive full dose-intensity combination chemotherapy. PATIENTS AND METHODS: In a phase III study patients received six cycles of BEP/EP (etoposide, and cisplatin, plus or minus bleomycin) or six cycles of BOP/VIP-B (bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, bleomycin). A subset were secondarily randomized to receive or not receive filgrastim. Filgrastim 5 microg/kg/day was administered subcutaneously on days 3 through 9 after each BOP and on days 6 through 19 after each VIP, BEP, or EP cycle. RESULTS: Eighty-five percent of 120 eligible patients randomized to filgrastim received at least six chemotherapy cycles compared with 70% of 130 patients randomized to not receive filgrastim (VCP = .003). Patients in the filgrastim-arm achieved significantly higher dose-intensities. Neutropenic fever occurred in 25 of 128 filgrastim-patients and in 38 of 129 non-filgrastim-patients (P = .052). Twelve and three toxic deaths occurred in the non-filgrastim- and filgrastim-arms, respectively. Nine of the 12 toxic deaths and all of the three toxic deaths were associated with febrile grade 4 neutropenia. Failure-free and overall survival were similar in both arms. CONCLUSION: During combination chemotherapy in patients with malignant germ cell tumors, the routine use of filgrastim significantly improved the delivery of the planned treatment schedule without effect on failure-free or overall survival. The use of filgrastim was associated with a clinically important reduction in the number of toxic deaths, confined to the experimental intensified-chemotherapy schedule. This study does not support the routine use of filgrastim during standard chemotherapy with BEP.

Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.

PURPOSE: This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS: Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS: Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION: With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group.

PURPOSE: To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). PATIENTS AND METHODS: A retrospective international survey of 373 patients with primary testicular DLCL. RESULTS: Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. CONCLUSION: Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.

Germ cell cancers in adult males are associated with a history of infantile pyloric stenosis.

Germ cell cancers (GCT) are the most common cancers of young men and are curable in at least 90% of cases. A number of aetiological factors have been identified which predispose to the development of these cancers, such as cryptorchidism and hernia. We report the association of GCT with infantile pyloric stenosis (IPS). The case records from 542 adult males with germ cell cancer arising from any site were screened for a history of pyloric stenosis requiring surgical treatment. Nine cases were observed (expected number = 2.168; chi squared = 21.5 (P < 0.001), standardised ratio = 4.15; 95% confidence interval 1.9-7.88). The recognition of rare associations of germ cell tumours may lead to the identification of genetic and environmental factors involved in their aetiology.

Prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET) combination chemotherapy for relapsed or refractory non-Hodgkin lymphoma.

27 patients with relapsed/refractory non-Hodgkin lymphoma (NHL) received combination chemotherapy with prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET). 25 patients are evaluable for response. 7 (26%) obtained a complete response and one (4%) a partial response. The median survival for the entire group was 6 months. 2 patients are currently alive without disease, 1 of whom has received further therapy. The regimen was intensely myelosuppressive, but was well tolerated. The complete response rate and median survival figures are comparable to previous studies of salvage therapy confirming the poor prognosis for relapsed NHL and emphasising the need for prospective randomised studies.

Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party.

In a retrospective study, data from 302 patients with metastatic testicular seminoma treated with chemotherapy between 1978 and 1990 in 10 European centres were analysed to evaluate the role, if any, of postchemotherapy treatment with irradiation. The primary endpoint of this study was the progression-free survival rate after chemotherapy with or without additional radiotherapy. This was related to the type of primary chemotherapy, sites and sizes of pre- and postchemotherapy masses, the extent of surgical resection after chemotherapy and the use of radiotherapy. 174 patients had residual disease at the end of chemotherapy. The most important prognostic factors for progression were the presence of any visceral metastases or raised LDH prechemotherapy, and the presence of residual disease at visceral sites after chemotherapy. Approximately half the patients with residual masses underwent postchemotherapy radiotherapy, with selection based predominantly on institutional practice. In patients receiving platinum-based chemotherapy, no significant difference was detected in progression-free survival whether or not radiotherapy was employed. Patients receiving BEP (bleomycin, etoposide and cisplatin) had a progression-free survival rate of 88% (95% CI, 80-96%) uninfluenced by postchemotherapy radiotherapy. In patients with residual masses confined to the abdomen after platinum-based chemotherapy, the absolute benefit to radiotherapy was estimated to be 2.3%. The potential benefit of postchemotherapy radiotherapy is minimal, and so it is concluded that the use of adjuvant radiotherapy to residual masses after platinum-based chemotherapy for metastatic seminoma is unnecessary.

Prognostic factors for patients with advanced seminoma treated with platinum-based chemotherapy.

Prognostic factors for 3-year progression-free survival (PFS) were defined in 286 patients with advanced seminoma treated with cisplatin-based chemotherapy at 10 European oncology units (no prior treatment: 236; prior radiotherapy: 50). Previously irradiated patients displayed a 69% PFS as compared to 87% in those presenting with advanced seminoma at the time of diagnosis (P = 0.009). In the univariate analysis, the extent and site of disease before chemotherapy and the level of serum LDH (< 2.0 versus > or = 2.0 x upper limit of normal) correlated with PFS in previously non-irradiated patients, but not in patients with prior radiotherapy. The multivariate analysis was, therefore, restricted to previously non-irradiated patients. The presence of non-pulmonary visceral metastases and a serum LDH level of > or = 2 x normal (N) proved to be independent prognostic factors. Based on these variables, two prognostic models were constructed and validated in an external data set of 166 comparable patients. For clinical use, Model 2 is recommended. The good-prognosis group comprises non-irradiated patients with stage II seminoma and any LDH level at presentation, or stage III and IV patients (with lung metastases only) whose serum LDH level is < 2 x N. These patients display a 94% 3-year PFS. The poor prognosis group includes all other patients with a 56% PFS. With this prognostic model, individualisation of the therapeutic approach may be considered in patients with advanced seminoma and a high risk of chemotherapy-related toxicity.

Measurement of antibodies to tubulin by radioimmunoassay.

A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses.

Changing role of chemotherapy in treatment of head and neck cancer.

The role of chemotherapy in the management of head and neck cancer includes treatment for recurrent disease and as an adjunct to conventional therapy with radiation and/or surgery in the primary treatment program. The best single agents, methotrexate and cisplatin, used for recurrent disease give response rates of 20 to 50 percent but of short duration. Results may be improved with combination chemotherapy, but often with increased toxicity. Prognostic factors that influence response are discussed. A newer role of chemotherapy in this disease is in the initial treatment program. Pretreatment chemotherapy can debulk these lesions prior to surgery and/or irradiation in up to 80 percent of patients. Controlled trials are in progress to determine the effect on cure rates. Chemotherapy utilized during radiotherapy has resulted in survival benefit in several studies. Post-treatment adjuvant chemotherapy still needs to be evaluated. The potential advantages and disadvantages of chemotherapy used in the initial treatment are discussed. Major strides have been made in the last decade in the treatment of head and neck cancer, and chemotherapy is assuming an increasingly important role.