M.J. Peckham

The radioresponsiveness of human tumours and the initial slope ofthe cell survival curve

Published data on the inherent radiosensitivity of human tumour cells has been analysed in order to reexamine the relationship between the initial slope of the cell survival curve and clinical radioresponsiveness. A clear positive correlation between these parameters is demonstrated. The surviving fraction at 2 Gy is shown to give good discrimination between resistant and sensitive tumour types.

HISTOPATHOLOGY IN THE PREDICTION OF RELAPSE OF PATIENTS WITH STAGE I TESTICULAR TERATOMA TREATED BY ORCHIDECTOMY ALONE

259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orchidectomy alone and monitored at one often centres in the United Kingdom were followed for a median of 30 months. 62 of the 70 relapses occurred in the first 18 months after orchidectomy. The 2-year relapse-free rate was 74%, falling to 68% at 4 years. Histological sections from 233 of the orchidectomy specimens were reviewed centrally. Four features independently predicted relapses: invasion of testicular veins, invasion of testicular lymphatics, absence of yolk-sac elements, and presence of undifferentiated tumour. An index, based on the number of these features observed, identified a high-risk subgroup of 55 patients who had a 42% relapse-free rate at 2 years.

ORCHIDECTOMY ALONE IN TESTICULAR STAGE I NON-SEMINOMATOUS GERM-CELL TUMOURS

53 patients with clinical stage I non-seminomatous germ-cell testicular tumours were entered into a prospective study to receive no treatment other than orchidectomy until unequivocal clinical evidence of metastases was established. Of this group, 9 men (17%) have relapsed, 8 within six months of orchidectomy. All 9 are alive and disease-free after chemotherapy. The relapse rate was higher in patients with malignant teratoma undifferentiated (embryonal carcinoma) primary tumours than in those with malignant teratoma intermediate (teratocarcinoma); 42.8 and 3.4%, respectively. The results were compared with those from 157 men treated by orchidectomy and radiotherapy for stage I disease. In this group, 49 patients (25.8%) relapsed and 85% of relapses occurred within one year of orchidectomy. The tempo relapse was identical for embryonal carcinoma and teratocarcinoma. Of 32 patients in whom serum markers were measured before orchidectomy, 24 (75%) had raised levels of alphafetoprotein and/or beta human chorionic gonadotropin. These preliminary results imply that routine lymphadenectomy or lymph node irradiation in clinical state I testicular non-seminoma may be unjustifiable.

COMBINED MANAGEMENT OF MALIGNANT TERATOMA OF THE TESTIS

Intensive chemotherapy with bleomycin and vinblastine was used as initial treatment in patients with advanced testicular teratoma and after relapse following lymph-node irradiation in patients with early-stage disease. Between January, 1976, and March, 1978, 84 patients, 28 with early disease and 56 with advanced disease, were treated. All 28 men with early-stage disease are alive and disease-free. Patients with advanced disease were divided into two groups. Patients with bulky multiple lung metastases and those with liver involvement did poorly, only 4 of 23 (17.4%) being disease-free. Conversely, patients with bulky abdominal nodes and those with limited lung disease did well, 17 of 21 previously untreated patients (80.9%) being alive and disease-free. Within the latter group, 16 patients were managed with chemotherapy and radiotherapy and/or surgery. Of these, 15 (93.4%) are disease-free.

The management of metastatic seminoma testis.

Clinical details of 85 men presenting with previously untreated metastatic seminoma are presented. In Stage II disease relapse rate was related to the size of metastases. In IIA (32 patients) the relapse rate was 9.4%; IIB (11 patients), 18.2%; and IIC (23 patients), 39.1%. The continuous disease‐free survival rate was significantly worse for IIC than IIA and IIB patients (P = 0.023). No instance of first relapse in supradiaphragmatic nodes was observed in 13 men with Stage II disease treated with irradiation limited to infradiaphragmatic nodes. In relapsing Stage IIC patients, extralymphatic metastasis was as frequent as abdominal relapse. On the basis of these observations, together with preliminary data in nine men receiving Cis‐platinum‐containing chemotherapy, all of whom are in complete remission, it is proposed that patients with Stage IIA and IIB disease should receive infradiaphragmatic irradiation with chemotherapy deferred until relapse. Stage IIC patients should receive chemotherapy initially, followed by irradiation. In Stage III and IV disease chemotherapy should be initial therapy with radiotherapy for bulky disease on an individualised basis. Moderate elevation of blood B‐HCG levels is not inconsistent with a diagnosis of pure seminoma and does not appear to influence adversely the outcome of radiotherapy.

Radiotherapy for Stage I seminoma testis: Results of treatment and complications

The results of treatment by infradiaphragmatic lymph node irradiation and orchiectomy in 232 patients with Stage I testicular seminoma seen between 1963 and 1983 are reported. Of this group, only five (2%) patients relapsed and none died from seminoma. Contralateral testicular tumours occurred in 12 patients and five developed second non-testicular malignancies. The acute and late morbidity of radiotherapy was low although 15 patients developed peptic ulceration. There was a significant association between prior abdominal surgery and a history of dyspepsia with ensuing peptic ulceration. Future management policy is discussed on the basis of these observations.

Orchidectomy alone for stage I seminoma of the testis.

Between 1983 and 1988, 113 patients with Stage I seminoma were managed after orchidectomy by surveillance rather than adjuvant radiotherapy. The actuarial risk of relapse at 3 years was 15.8% (95% confidence interval, 7.8% to 23.8%). All 13 patients who experienced a relapse are currently in remission (4 to 45 months after salvage therapy), although 5 suffered second relapses requiring further treatment. Close surveillance is a safe alternative to adjuvant radiotherapy in Stage I seminoma. However, the policy requires prolonged observation of patients with intensive use of resources. Therefore, adjuvant radiotherapy should be considered the treatment of choice.

Extranodal non-Hodgkin's lymphoma presenting in the testicle. A clinical and pathologic study of 24 cases

Twenty‐four cases of extranodal non‐Hodgkins lymphoma presenting in the testicle are reviewed. All cases are diffuse lymphoma by the Rappaport classification. Cases clinically staged as I/II, (18/24) show a prolonged survival compared with those clinically staged as III/IV (6 of 24). Progressive involvement of either the lymphoid tissue in Waldeyers ring or adjacent structures in the nasopharynx or oropharynx was noted in 22% (4 of 18) of Stage I/II cases. In 2 of the 24 (8%), there was asynchronous involvement of the opposite testicle. In patients with Stage I/II disease radiation therapy to the pelvic and paraaortic lymph nodes following inguinal orchidectomy is recommended. Systemic chemotherapy is recommended to follow radiation therapy unless bulky abdominal disease is present in which case it should precede radiation therapy. Prophylactic radiation of the opposite uninvolved testis is not recommended.

Children fathered by men treated for testicular cancer.

Children fathered by 27 testicular cancer patients treated with radiotherapy, 25 treated with chemotherapy, and 57 control men (46 community controls and 11 Stage I testicular cancer patients) were examined for evidence of congenital malformations. The proportion of malformations in children in the treatment group did not differ from that in children in the control group or from incidence rates for malformations in the general population. Our results suggest that treatment for testicular cancer should not constitute a reason for advising termination of pregnancy, although numbers were too few to detect a relative risk smaller than 3 X 2. More observations are needed to provide a definite answer.

The radiobiology of human neuroblastoma

The radiation response of a human neuroblastoma xenograft HX138 has been studied in vitro and in vivo using single cells in suspension, multicellular spheroids, and xenografts in immune-suppressed mice. End-points used were growth delay and clonogenic cell survival. Growth delay experiments with spheroids and xenografts showed a high degree of radioresponsiveness. Cell survival curves obtained from all systems were characterised by the lack of a shoulder. An increase in Do of the cell survival curve was seen after irradiation of intact spheroids and xenografts, perhaps due to the presence of a contact effect. Cellular capacity for split-dose recovery in vitro was modest. Delayed assay experiments using spheroids and xenografts showed some potentially lethal damage (PLD) repair in vitro but not in vivo. The results show this human tumour line to be intrinsically highly radiosensitive, with a limited repair capacity.