George Quong

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.

Assessing the impact of FDG-PET in the management of anal cancer

PURPOSE To assess the utility of FDG-PET in anal cancer for staging and impact on radiotherapy planning (RTP), response and detection of recurrent disease. METHODS AND MATERIALS Fifty histopathological anal cancer patients were reviewed between 1996 and 2006. The median age was 58 years (range 36-85) with 19 males:31females. Clinical assessment with CT was compared to PET. Impact on management, disease response, recurrence and metastases was evaluated. RESULTS The non-PET staging was Stage I(8), Stage II(18), Stage III(22), and Stage IV(2)s. The primary was strongly FDG avid in 98% with non-excised tumors compared to CT (58%). PET upstaged 17% with unsuspected pelvic/inguinal nodal disease. Pre-treatment PET identified 11 additional by involved nodal groups in 48 patients causing RTP amendments in 19%. Post-treatment PETs at median 17 weeks (range 9-28) showed complete responses in 20 (80%) and 5 (20%) partial responses (PR). PRs were biopsy positive in 2 and negative in 3. Fifteen had follow-up scans of which all nine PETs detected recurrences were pathologically confirmed. CONCLUSIONS Anal cancer is FDG-PET avid. PET upstages 17% and changes the RTP in 19%. PET can aid in anal cancer staging and identification of residual disease, recurrent/metastatic disease but warrants further prospective studies.

A randomized trial comparing 35 Gy in ten fractions with 60 Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma

A randomized prospective clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated, short course radiotherapy in poor prognosis patients with high grade glioma. The primary endpoint was overall survival.

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 Hodgkins disease. METHODS AND MATERIALS A retrospective review of 64 patients with lymphocyte predominant Hodgkins 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 (Hodgkins 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-Hodgkins 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-Hodgkins lymphoma. CONCLUSION Our results are consistent with major reported series displaying no differences between any of the subgroups of lymphocyte predominant Hodgkins disease.

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.

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 Hodgkins 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.

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care

PURPOSE Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkins disease treated solely by irradiation in Australia and New Zealand. METHODS AND MATERIALS Patients with supradiaphragmatic Hodgkins disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. RESULTS Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year actuarial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkins lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. CONCLUSIONS The Australasian experience of early stage Hodgkins disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

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

PURPOSE To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkins 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 Hodgkins 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.