Organ preservation for the treatment of contralateral testicular seminoma.

PURPOSE: Local excision of germ cell tumor in the remaining testicle followed by a modest dose of irradiation is an alternative to orchiectomy. This organ sparing technique provides superior quality of life and reduces the need for lifelong hormone replacement. MATERIALS AND METHODS: We treated two patients with contralateral seminomas with organ preservation. Both patients received postoperative irradiation to the remaining testicle to a dose of 20 Gy in 10 fractions and 19.8 Gy in 11 fractions. RESULTS: Both patients are alive with no evidence of disease more than 3 years since the completion of their treatments. They both have reduced but preserved androgen production and retained their virility. They both are azospermic. CONCLUSION: We conclude that organ preservation for the treatment of contralateral testicular seminoma is a superior alternative to orchiectomy of the remaining testicle. It preserves male hormone production with equal survival outcome expectations.

One hundred years of radiation therapy: a tribute.

The history of radiation therapy is fascinating and tragic. As we celebrate the centennial of Wilhelm Roentgen's discovery, physicians should remember the pioneers who made it possible for contemporary radiation oncologists to practice with the highest degree of sophistication.

Sclerosing basal cell carcinoma: management with electron beam therapy.

There are two types of sclerosing basal cell carcinoma (BCC), one entirely with this histology and a second with a prominent sclerosing component. Sclerosing BCC and nodular BCC with a sclerosing component often represent a difficult diagnostic and therapeutic challenge.

Development and applications of an animal model for human tumor xenografts.

Wistar rats treated with cyclophosphamide (4x 10 mg/kg), total lymphoid irradiation (9.0 Gy; dose rate 0.60 Gy/min) and cyclosporin A (15 mg/kg, daily, orally) developed a state of immune suppression permitting the growth of human tumor xenografts. Immunosuppression was monitored by lymphocyte counts, serum IgG determination. PHA and Con A lymphocyte-responses, proportion of B cells and histopathological studies of the lymphoid organs. The lymphocyte counts, IgG levels, PHA and Con A stimulation values remained severely depressed, during the period of cyclosporin A administration. Repopulation of the paracortical areas of the lymph nodes and the peri-arteriolar sheaths of the spleen did not occur, neither the reconstruction of the germinal centers in these organs. The thymus underwent severe atrophy. Seven of eight different types of human tumors were successfully xenografted in the immunomodified rat. The xenografted tumors maintained their original morphologic features and the mitotic rate did not change during subsequent transplantations.

Surgery and radiation therapy in the management of craniopharyngiomas.

Twenty-nine patients with histologically confirmed craniopharyngioma were treated from 1960 to 1978, inclusive. Twelve patients were below the age of 15 years, the remaining were adults. Seventy-five percent (9/12) of the patients below the age of 15 showed increased intracranial pressure at presentation and 58% (7/12) showed visual disturbances. In the adult group, 47% (8/17) presented with increased intracranial pressure and 88% (15/17) with visual disturbances. Hormonal, mental and behavior changes were almost equally distributed in both age groups. All patients underwent craniotomy, with subtotal resection of the tumor. Three adults died of postoperative complications (10%), of whom two died of pulmonary emboli and one of cerebral hemorrhage. Of the remaining 26 patients, 13 received immediate postoperative radiotherapy to a total dose of 50.0 to 56.0 Gy, in a target volume including the sellar and parasellar region during an overall treatment period of five to six weeks. All patients were evaluable with a minimum follow-up of four years since they finished their treatment or until death. The five-year recurrence-rate in the group that did not receive postoperative radiation therapy was 45% (5/11 patients) and the five-year rate of death of disease in this group was 27% (3/11 patients). For the group that received immediate postoperative radiation therapy the five-year recurrence-rate was 11% (1/9 patients) and no death of disease was observed in this group. This difference between the two groups was not significant. The corresponding 10-year rates were 71% (5/7 patients) for recurrence and 57% (4/7 patients) for death of disease in the group without, and in the group with immediate postoperative radiation therapy the rate was 25% (2/8 patients) for recurrence and 0 for death of disease. This difference turns out to be significant. Critical analysis of the morbidity in patients surviving after treatment showed no adverse effect on the visual or endocrine status of the group that received postoperative irradiation. It is concluded that in the management of patients with craniopharyngiomas, postoperative irradiation after subtotal resection improves the prognosis of the patient and does not add to visual or endocrine morbidity.

Planned preoperative radiation therapy vs. definitive radiotherapy for advanced laryngeal carcinoma.

In the period 1970-1980 inclusive, 191 patients with T3T4 laryngeal carcinoma (glottic: 63 and supraglottic: 128) received either definitive radiation therapy (RT) (60-65 Gy in 6-7 weeks) or planned preoperative radiation therapy (25 Gy in 5 equal daily fractions of 5 Gy) followed by laryngectomy with or without neck dissection (RT + S). Selection for RT vs. RT + S was based on medical operability and/or patient's refusal to undergo surgery. All patients are evaluable with minimum of 2 years observation. Crude 5 and 10-year survival probability for 32 patients with glottic localization who received RT is 55% and 38% vs. 65% and 65% respectively for 31 treated with RT + S. For 52 patients with supraglottic site who received RT, the 5 and 10-year survival is 44% and 44% vs. 82% and 60% for 76 patients treated with RT + S.

Evaluation of short-course preoperative irradiation in the treatment of resectable bronchus carcinoma: long-term analysis of a randomized pilot-study.

A randomized pilot-study on patients with resectable non small-cell lung carcinoma was conducted from December 1971 to May 1976 inclusive. Patients were randomly assigned to receive preoperative irradiation to the mediastinum followed by surgery (RT + S), or to be treated by surgery only (SO). A total of 33 patients clinically staged as T1-2, N0, M0 histologically confirmed bronchus carcinoma were entered onto the study. Sixteen patients were assigned to RT + S and 17 patients received SO. There were 3 operative mortalities, all of them in the SO group. A total of 28 patients, 14 in each group are evaluable, with a minimum period of observation of 7 years. Preoperative irradiation consisted of a Telecobalt photon-beam applied to the mediastinum as anterior and posterior portals. The thoracic spine was protected on the posterior portal by a narrow lead block. A total dose of 20 Gy calculated in the mid plane was given in 5 equal fractions each of 4 Gy administered on 5 consecutive days: Monday through Friday; patients were operated on the following Monday after the week-end. Surgical treatment was similar for both groups and consisted of lobectomy or pneumonectomy, depending on the size and site of the primary tumor. Analysis of the survival data showed an absolute crude 5 years survival rate of 58% for patients who received RT + S versus 43% for SO. The corrected actuarial 5 and 10 years survival rates are 78 and 69% for the group that received RT + S, and 67 and 55% for the group treated by SO, respectively. Nineteen patients were treated more than 10 years ago. Four of 8 (50%) treated by RT + S are alive with no evidence of disease (NED), and 3/11 (28%) treated by SO are alive with NED. The median survival period for the group that received RT + S is 72 months versus 30 months for the group treated by SO. Analysis of the adequacy of surgical resection based on histological examination of the operative specimen showed higher incidence of radical resection in the group that received RT + S (57 versus 28.5%). It is concluded that the treatment protocol of preoperative radiation therapy as outlined is well tolerated and the results are encouraging.

Primary radiation therapy for T1 glottic cancer. Factors influencing local control.

One hundred and seventy-four patients with early glottic cancer received radiation therapy on the kV250 and cobalt 60 machines. Crude survival rates at 5, 10 and 15 years were 83%, 73% and 60%, respectively. Salvage surgery for locoregional recurrences was successful in 85% of the patients. A significantly higher failure rate was noted in patients with a pre-existing chronic laryngitis, with lesions confined to the left vocal cord and in those treated with KV250 irradiation. The rate of second primaries in this case material was 11%, 70% of which were noted in the respiratory tract. Megavoltage radiotherapy offers excellent chances for cure in T1 laryngeal carcinoma with preservation of good voice in most patients. Patients with chronic laryngitis carry a high risk of local recurrence and therefore should be considered for primary conservation surgery.

Four years experience with a mercury shielded irregular field system (MSIFS).

A mercury shielded irregular field system (MSIFS) has been in use in our department since January 1979. The system is described and illustrated. Experience in treating 225 patients demonstrated that the system is accurate and reproducible. The system offers a choice of shielding efficiency in a transmission range from 100 to 3.5% for 18 MV photons. Routine measurements of mercury vapor concentration in the treatment room showed values below 0.02 mg Hg/m3 air. (The maximum acceptable concentration in The Netherlands is 0.05 mg Hg/m3 air.) It is concluded that the system is cost-effective, easy to use, and flexible and safe.

Sequential non-cross-resistant chemotherapy regimens (MOPP and CAVmP) in Hodgkin's disease stage IIIB and IV.

Fifty consecutive patients with advanced Hodgkin's disease were treated in a multicentre study with 6 cycles of an alternating scheme of MOPP and CAVmP followed by irradiation to a dose of 20 Gy. The objective was to increase complete remission (CR) and cure rates by alternating two effective noncross-resistant regimens with subsequent consolidation of the remission by irradiating bulky nodes. A total of 47 patients completed the treatment and are evaluable. In the first 13 patients the irradiation fields amounted to a total or subtotal nodal irradiation with inclusion of the spleen. In case of organ involvement the affected organ was also included in the irradiation field. The irradiation protocol was later changed to an irradiation of the initially involved sites because of severe leucopenia and thrombopenia. After completion of the chemotherapy 32 (68%) patients (for Stage IIIB and IV patients: 63% and 71%, respectively) achieved a CR, after ending the radiotherapy the percentage of CR increased to 87% (for stage IIIB and IV patients: 90% and 86%, respectively). Five of the patients relapsed in an irradiated and nonirradiated area, three patients in a nonirradiated field. The actuarial 3-year survival rate for the entire group was 86% and for patients in CR 94%. The relapse-free survival was 73%. It is concluded that this alternating chemotherapy scheme followed by irradiation is at least equally effective as MOPP treatment in achieving a CR, and is probably superior in terms of survival.

Malignant tumours of the nasopharynx: retrospective review of 74 cases.

Seventy-four patients with histologically confirmed malignant tumours of the nasopharynx were treated by the Departments of ENT and Radiotherapy of the Sint Radboud Academic Hospital, Nijmegen, The Netherlands. Selected prognostic factors were examined. The 5-year overall survival for the malignant epithelial tumours was 35%. The number of patients treated was too small to reach definite conclusions with respect to age and histology as prognostic factors. Staging, however, seems to be of value and it is suggested that the classification proposed in Kyoto, Japan, 1977 be adopted because it offers a better relationship between clinical staging and prognosis. From our data it appeared that treatment failure occurs mainly because of advanced initial tumour stage or distant metastasis; 40% of patients with initial locoregional control died because of distant metastasis. As half of the patients with distant metastasis presented with 'early' tumour stages (T1, T2, T3a), we strongly recommend adding systemic chemotherapy to the primary treatment of nasopharyngeal tumours.

Growth pattern of tumor xenografts in Wistar rats after treatment with cyclophosphamide, total lymphoid irradiation and/or cyclosporin A.

Wistar rats treated with cyclophosphamide, total lymphoid irradiation (TLI), and/or cyclosporin A (CSA) develop a state of immune suppression permitting the growth of tumor xenografts. Experiments were carried out on this newly developed model to investigate the growth patterns of a mouse osteosarcoma and a human colon adenocarcinoma. The combination of cyclophosphamide and CSA permitted a limited period of growth of the mouse osteosarcoma with a tumor take rate of 66%. No takes were observed with the human adenocarcinoma. The combination of cyclophosphamide and TLI resulted in a period of immunosuppression followed by recovery of the immune status. During the period of immunosuppression, tumor xenografts showed a 100% take rate. The most efficient immunosuppression was achieved by a combination of cyclophosphamide, TLI and CSA administered on alternate days. Wistar rats subjected to this treatment showed prolonged tolerance to mouse osteosarcoma and human adenocarcinoma xenografts. There was no alteration in the tumor doubling time or histological morphology of the xenografts in the adapted host as compared with those in the donor tumors. The tumor growth curve showed a pattern of initial growth, a period of stagnation, followed by a steady but slower growth phase. The significance of the results and the advantages of the rat model described in this paper for human tumor xenotransplantation are discussed.

Total lymphoid irradiation in the Wistar rat: technique and dosimetry.

The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization of lymph nodes, thymus and spleen. A practical advantage was found in the simultaneous irradiation through two portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetry, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments.

Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation.

Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

Planned preoperative radiation therapy for advanced laryngeal carcinoma.

One hundred ten patients with predominantly advanced laryngeal carcinoma were treated in the period 1969-1978 with planned preoperative radiation therapy followed by surgery. Site distribution was: 63 supraglottic, 26 glottic, 15 transglottic and 6 subglottic. There were 4 Stage II patients, 66 Stage III and 40 Stage IV. Preoperative radiation therapy consisted of Telecobalt irradiation to a total dose of 25 Gy given to a target volume encompassing the larynx and regional neck nodes, given in 5 equal daily fractions of 5 Gy in 5 consecutive days. Surgery was performed 2 days later. Total laryngectomy was performed on 48 patients, total laryngectomy with neck dissection on 55 patients, supraglottic laryngectomy on 5 and supraglottic laryngectomy with neck dissection on 2 patients. Crude actuarial 5 and 10 year survival probability for the whole group is 71 and 61%, respectively. The corrected 5 and 10 year survival is 75%. For patients with T3-T4-N0 tumors 5 and 10 year survival probability is: crude 65 and 58%, and corrected 70% respectively. For T3-T4-N+ crude: 75 and 60% and corrected: 78%. Of 110 patients, one died postoperative, three died of intercurrent disease, five died as a result of second malignancy, and 23 died of their larynx carcinoma: 12/23 because of locoregional failure, and 11/23 because of distant metastasis. We concluded that short intensive preoperative radiation therapy and surgery offer a high cure rate in the treatment of advanced resectable laryngeal carcinoma. The merits of this technique are outlined in the text.