Mantle irradiation alone for clinical stage I-II Hodgkin's disease: long-term follow-up and analysis of prognostic factors in 261 patients.

PURPOSE: To evaluate mantle radiotherapy (MRT) alone as the initial therapy of patients with clinical stage (CS) I-II Hodgkin's disease (HD). PATIENTS AND METHODS: We performed a retrospective study of patients treated with MRT alone for CS I-II supradiaphragmatic HD between 1969 and 1994. Prognostic factor analysis was performed for progression-free survival (PFS) and overall survival (OS). Outcome was also assessed in favorable cohorts defined in the literature. RESULTS: There were 261 eligible patients. The median follow-up period for surviving patients was 8.4 years (range, 1.8 to 27.4 years). The 10-year OS rate was 73%. Multifactor analysis for OS showed that age was the only important prognostic factor. The 10-year PFS rate was 58%. On multifactor analysis for PFS, the most important prognostic factors were clinical stage, B symptoms, histology, number of sites, and tumor bulk. The 10-year PFS rate for lymphocyte-predominant disease was 81% for stage I and 78% for stage II. In favorable patient cohorts defined in the literature, the 10-year PFS rate ranged from 70% to 73% for the whole group and from 71% to 90% in patients with favorable stage I disease, but only from 48% to 57% in patients with favorable stage II disease. On competing-risks analysis, the cumulative 10-year incidence of first site of failure in the para-aortic/splenic region alone was 10.5%. Sixty percent of relapsed patients remain progression-free at 10 years after chemotherapy salvage. CONCLUSION: These results support the use of MRT alone in patients with favorable CS I HD and CS I-II HD with lymphocyte-predominant histology. The remainder of patients with CS I-II HD require more intensive treatment.

A study of splenic irradiation in chronic lymphocytic leukemia.

A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemaglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

Lymphocyte predominant Hodgkin's disease: a clinicopathologic comparative study of histologic and immunophenotypic subtypes.

PURPOSE: To compare the clinicopathologic features of the histologic and immunophenotypic subgroups of lymphocyte predominant Hodgkin's disease. METHODS AND MATERIALS: A retrospective review of 64 patients with lymphocyte predominant Hodgkin's disease treated at the Peter MacCallum Cancer Institute, Melbourne, was performed. Nodular and diffuse histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections. Immunophenotyping with monoclonal antibodies L26 (B-cell origin) and Leu M1 (Hodgkin's phenotype) were available in 36 patients. RESULTS: The estimated freedom from progression and estimated overall survival at 10 years was 74% standard error (SE 5.8%) and 85% (SE 5.2%), non-Hodgkin's respectively. There were no significant differences in freedom from progression or overall survival when nodular and diffuse histology were compared. Similarly the presence of B-cell markers did not influence prognosis. There was only one case of secondary non-Hodgkin's lymphoma. CONCLUSION: Our results are consistent with major reported series displaying no differences between any of the subgroups of lymphocyte predominant Hodgkin's disease.

Primary central nervous system lymphoma: age and performance status are more important than treatment modality.

PURPOSE: To assess prognostic factors and treatment modalities of patients with primary central nervous system lymphoma (PCNSL) in terms of response rates, patterns of failure and overall survival. METHODS AND MATERIALS: Sixty-two patients presenting with PCNSL between 1982 and 1994 at Peter MacCallum Cancer Institute with no evidence of human immunodeficiency virus infection were included in the study. Their median age was 60 years; World Health Organisation (WHO) performance status was > or = 2 in 85%. All patients were planned to receive whole brain irradiation; 7 also received spinal irradiation. The median planned dose to the target volume was 50.4 Gy. Twenty patients were planned to receive chemotherapy as well. Patients were followed up to June 20, 1995, giving a median follow-up for 14 surviving patients of 5.4 years, range 0.3 to 10.2 years. RESULTS: The clinical response rate to treatment was 77% [95% confidence interval (CI) 65 to 87%]. The estimated median overall survival was 20.6 months (CI 12.4 to 33.4 months). On univariate analysis male gender, age <60 years, WHO performance status < or = 1, treatment to the target volume > or = 45 Gy, and treatment with additional chemotherapy, were associated with a significantly better overall survival (p < 0.05). On multivariate analysis only age and performance status remained significant prognostic variables. Relapse involved the central nervous system or cerebrospinal fluid (CSF) in all patients with known sites of relapse except three who had ocular relapse only. There was a low incidence of relapse in the initial brain site (23% of known cases) and a high incidence (50%) of CSF/spinal cord relapse. Of 48 deaths, 15 were related to initial or subsequent treatment. CONCLUSIONS: Patient outcome is strongly influenced by age and performance status. Studies suggesting better survival for patients treated with chemoradiation may reflect patient selection rather than treatment variables. Optimal management remains to be defined. The high CSF/spinal relapse rate deserves particular attention.

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic imaging to radiotherapy planning in lung cancer.

A retrospective analysis was performed to determine whether coronal thoracic [18F]fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) scans, if viewed at the time of radiotherapy (RT) planning, would have influenced the anterior-posterior (AP) RT volumes that were administered to a group of unoperated lung cancer patients. Viewing of PET and diagnostic images enabled a qualitative assessment of whether abnormal thoracic PET activity was present in areas regarded as normal by diagnostic imaging; this would, therefore, have influenced the RT volume if done prospectively. Additionally a method of graphical co-registration was devised to quantitate the adequacy of coverage of each patient's abnormal PET activity by his/her actual RT field. Of 15 patients analyzed, 26.7% (four patients) would have had their RT volume influenced by PET findings, highlighting the potential value of PET in treatment planning.

Dose errors in the near field of an HDR brachytherapy stepping source.

The dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter with an active stepping source (Nucletron microSelectron HDR source) with a dwell length of 2 cm was calculated using Monte Carlo code MCNP 4.A. The source step sizes were 1 cm and 0.25 cm. The Monte Carlo (MC) results were used for comparison with the results calculated with the Nucletron brachytherapy planning system (BPS) formalism, first with BPS variants and then with its respective MC calculated radial dose function and anisotropy function. The dose differences at point P calculated using the BPS formalism and variants are +15.4% and +3.1% for the source step size of 1 cm and 0.25 cm respectively. This reduction in dose difference is caused by the increased importance of errors in the anisotropy function with the smaller step size, which counter the errors in the radial dose function. Using the MC calculated radial dose function and anisotropy function with the BPS formalism. 1% dose calculation accuracy can be achieved, even in the near field, with negligible extra demand on computation time.

Dosimetry errors in endovascular high-dose-rate brachytherapy.

Monte Carlo data were used to demonstrate the dosimetry of the microSelectron high-dose-rate (HDR) iridium 192 (192Ir) stepping source. These data were used to assess the accuracy of the Nucletron brachytherapy planning system (BPS version 13) for peripheral vessel endovascular brachytherapy. Dose rates from the high-dose-rate (HDR) source are calculated using the Monte Carlo code MCNP4A. Calculations are made at 0.25-cm intervals in the longitudinal direction on sleeves of radii of 1 and 0.25 cm. The Monte Carlo data are summed and weighted to simulate the longitudinal dose distribution at a distance of 1 and 0.25 cm from an 192Ir source stepping through a straight pathway. A comparison is made between the simulated Monte Carlo dosimetry and the Nucletron brachytherapy planning system's dosimetry. This study illustrates and quantifies the dosimetric errors at small distances associated with a point source dose calculation algorithm. The effects of step size, dwell time optimization, and active length on the accuracy of BPS v.13 for HDR endovascular brachytherapy are demonstrated.

Verification of brachytherapy dosimetry with radiochromic film.

The aim of this work is to empirically validate the optimized dose distribution calculated by the Nucletron Brachytherapy Planning System (v. 13.3) at a distance of 1.0 cm from a stepping source of high-dose-rate-iridium 192 (192Ir). The longitudinal dose distribution at 1.0 cm from a straight pathway of multiple-source positions is measured using radiochromic film and compared with the planning system's calculated results. The optical density of the exposed films was determined with a modified Scanditronix film scanner, and the film was calibrated with 192Ir using manually calculated exposure times. A calibration equation was used to convert scanner output to dose. Our results illustrate the significance of exacting geometry in the experimental setup due to the inverse square law and the small distances involved. The dose distribution calculated by the Nucletron Brachytherapy Planning System (v. 13.3), at a distance of 1.0 cm, is validated to within +/-4% of the measured dose distribution. The advantages and limitations of radiochromic film as a dosimetry tool are also addressed in this work.

Standard linear plans in single channel high dose rate brachytherapy: a dosimetric analysis.

The use of standard linear plans is proposed for single channel intraluminal High Dose Rate brachytherapy. This technique employs the optimized dwell times derived from a straight line within a curved geometry. Such standardization of the planning procedure ensures expedient delivery of treatment. The 3-D dose distribution resulting from the use of standard linear plans within various curved geometries is investigated. In this study a comparison is made between the dose delivered to the perimeter of the target volume from both standard linear plans and individually optimized plans. Our results demonstrate that the use of a standard linear plan is acceptable in curved geometries, given the current practice of dose and volume specification for high dose rate intraluminal brachytherapy.

Radiotherapy in the management of solitary extramedullary plasmacytoma.

BACKGROUND: Solitary extramedullary plasmacytoma (SEP) is a rare tumour for which the standard treatment remains local radiotherapy (RT). We present a study of a multi-institutional experience, between 1980 and 1999, in an attempt to better understand the natural history of SEP and to identify possible prognostic factors. METHODS: The records at Radiation Oncology Victoria and Peter MacCallum Cancer Centre, Melbourne, were used for the identification of patients. The inclusion criteria were as follows: (i) histological confirmation of clonal plasma cells involving a single extramedullary site with or without lymph node involvement; (ii) no histological evidence of bone marrow involvement; (iii) no evidence of distant bone lesion on radiographic skeletal survey (bone erosions adjacent to the primary thought to be due to contiguous involvement were permitted) and (iv) no anaemia, hypercalcaemia or renal impairment due to plasma cell dyscrasia. RESULTS: A total of 16 patients was identified, with a median follow up of 66 months (range 12-211 months). The head and neck region accounted for the majority of presentations (88%). Among all patients, a serum mono-clonal paraprotein was found in three patients and bone erosion was identified in seven patients. All patients received local RT, although two patients also received elective nodal irradiation (ENI). The median RT dose was 45 Gy (range 40-50.4 Gy). Local control was achieved in all patients (100%), however, regional recurrence outside the RT fields occurred in 2/16. Multiple myeloma (MM) developed in five patients, all within 5 years. The predicted 10-year myeloma free survival is 75% and 10-year overall survival is 54%. CONCLUSION: RT can achieve excellent local control of SEP. The rate of conversion to MM is 31%. Moderate dose RT of at least 40 Gy using limited radiation fields is recommended, although ENI should be considered if toxicity is not increased.

Anaesthetic complications of mediastinal masses and superior vena caval obstruction.

Two patients with mediastinal tumour and superior vena caval obstruction who, after general anaesthesia, experienced respiratory difficulties requiring intubation or reintubation are presented. Possible aetiological mechanisms are discussed in relation to these cases.

Leiomyosarcoma of the rectum: what role does adjuvant therapy play?

Leiomyosarcoma of the rectum is an exceedingly rare malignancy and for this reason the literature fails to provide definitive management guidelines with regard to the place of adjuvant therapies. The role of radiotherapy (RT) is often downplayed on the basis of articles written at a time when state-of-the art RT equipment was unavailable. A case of leiomyosarcoma of the rectum is presented and the literature is reviewed. Because the rarity of this tumour type virtually precludes a prospective randomized trial of adjuvant therapies, the authors recommend (in otherwise fit patients) postoperative pelvic RT because its morbidity is minimal. Smaller tumours may benefit to a greater extent than those lesions that are large at presentation and thereby run a worse clinical course.

Infradiaphragmatic Hodgkin's disease, long term follow-up of a rare presentation.

Hodgkin's disease limited to the infradiaphragmatic region was seen in 30 of 306 (9.8%) of all Stage I and II patients referred to the Peter MacCallum Cancer Institute between 1968 and 1980. The male:female ratio was 2.3:1 with median age of 43.5 years at presentation. Of the seven patients with clinical stage (CS) IA-IIA disease who had staging laparotomy and splenectomy only one CSIIA patient had splenic involvement. The patients were staged as pathological stage (PS) IA 2, PSIIA 5, CSIA 4, CSIIA 10, CSIIB 9. Primary treatment was by radiation in 24 patients, combination chemotherapy in five and surgical excision in one. Twenty-five patients achieved complete response. Relapse free survival (RFS) at five and ten years was 59% and the five and ten-year survival was 75% and 67% respectively. On univariate analysis the significant prognostic factors for RFS and survival were stage, constitutional symptoms and presence of bulky disease. Using Cox regression analysis the only significant variable for RFS and survival was bulky disease (p = 0.01, 0.02). A treatment policy for patients with infradiaphragmatic Hodgkin's disease is recommended.

The utility of the Philips SRI-100 Real Time Portal Imaging Device in a case of postoperative irradiation for prevention of heterotopic bone formation following total hip replacement.

The new Radiation Oncology Department at the Heidelberg Repatriation Hospital in Melbourne, Australia commenced operation in June 1992. As part of quality control the Philips SL-15 linear accelerator was fitted with the Philips SRI-100 Real Time Portal Imaging Device (RTPID), the first such apparatus in Australia. One of its major advantages over older systems is its ability to provide a permanent hard copy of the image of the field treated. The computer image can be immediately manipulated and enhanced on the screen (with respect to such qualities as brightness and contrast) prior to the printing of the hard copy. This is a significant improvement over the more cumbersome older port films that required developing time, without any pre-assessment of the image quality. The utility of the Philips SRI-100 RTPID is demonstrated in the case of a patient irradiated soon after total hip replacement, as prophylaxis against heterotopic bone formation (HBF). The rapidity and quality of image production is a major advantage in these patients where post-operative pain may result in positional change between film exposure and image production. Extremely accurate shielding block position is essential to shield the prosthesis (and allow bone ingrowth for fixation) whilst avoiding inadvertent shielding of the areas at risk for HBF. A review of the literature is provided.

Use of digitally reconstructed radiographs in radiotherapy treatment planning and verification.

The authors present 3 years of experience in using digitally reconstructed radiographs (DRR) for radiotherapy planning and verification. Comparison is made with simulation film (SF), to illustrate the advantages of DRR over SF. Emphasis is placed on using the appropriate equipment and applying the correct technique. A brief discourse on the principle of CT imaging is presented to illustrate the operation of CT software and optimization of image display for axial slices and DRR. Emphasis is placed on the application of clinical knowledge to enhance the usefulness, as well as the technical quality, of the DRR. Illustrative examples are given.

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients.

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.