The TNM classification of prostate cancer.
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Biomedical subjects
Publications and source records attributed to M K Gospodarowicz.
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Between 1967 and 1988, 22 patients were treated at The Princess Margaret Hospital (PMH) for localized (stage IE) non-Hodgkin's lymphoma (NHL) presenting with spinal extradural compression. The median age of the patients was 55 years (range 18-76). Back pain (20 patients) and leg weakness (18 patients) were the commonest complaints at presentation. Seven patients (30%) were non-ambulatory (paraplegic or severely paretic) and four had imparied sphincter function. Diffuse histiocytic lymphoma (12 cases) was the commonest histology. All patients initially had laminectomy decompression and were referred to PMH post-operatively. One patient (with coincident metastatic carcinoma of the breast) was treated palliatively. The remaining 21 patients received radical post-operative treatment: radiation therapy (XRT) alone in 12 cases (25-45 Gy), radiation therapy plus systemic combination chemotherapy (combined modality therapy, CMT) in 9 cases. The overall actuarial survival for the radically treated patients was 55% at 10 years and there was a significant difference (p = 0.037) between those treated by XRT alone (33%) and those who received CMT (86%). Only one patient from each treatment group failed locally but the distant recurrence-free survival for the XRT group was 32% compared to 100% for the CMT group (p = 0.017). One patient developed primary central nervous system (CNS) relapse. The functional results of treatment were excellent: 19 of the 21 radically treated patients regained or retained normal ambulatory status and the remaining two patients had only minor disability. Decompressive surgery and radiotherapy for localized extradural lymphoma ensures a high rate of local control and functional recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.
A review of the Princess Margaret Hospital experience over the last 20 years in treating clinically staged patients with stage I and II Hodgkin's disease was performed to analyse the impact of patient selection and extended field radiation on relapse and survival. Of the 878 patients with stage I and II Hodgkin's disease, 521 with clinical stages I and II received radiation alone as the initial treatment. The actuarial survival for all stage I and II patients was 85.1% at 5 years and 76.2% at 10 years, and for clinically staged patients treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate (RFR) for all clinical stage I and II patients treated with radiotherapy (RT) alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors for RFR and survival included age, stage and histology. In addition, the extent of radiation was identified as an independent prognostic factor for survival as well as for relapse. The RFR for those treated with involved field RT was 58.4% at 5 years and 50.5% at 10 years; for patients treated with mantle RT, 69.9 and 65.6%, and those treated with extended field RT 77.4 and 75.8%, respectively. In a highly selected group of patients with no adverse features, i.e. with stages IA-IIA, lymphocyte predominant or nodular sclerosis histology, erythrocyte sedimentation rate < 40, age < 50, no large mediastinal mass, and no E-lesions--the policy of mantle RT (M) and extended field RT (EF) produced comparable 5-year relapse-free rates (M, 84.9%; EF, 87.1%; P = 0.53). We conclude that a policy of treatment selection based upon clinicopathological prognostic factors and the use of extended field RT confers excellent results in the treatment of clinical stage I and II Hodgkin's disease.
Twenty seven adult patients with newly diagnosed non-Hodgkin's lymphoma localised to either bone (Stage IE) or bone and regional lymph nodes (Stage IIE) were treated between 1967 and 1988. Median age was 53 years and the commonest histology (21 patients) was diffuse histiocytic lymphoma. Twenty-four patients were treated radically: 15 with radiation therapy (XRT) alone and nine with chemotherapy plus radiation therapy (CMT). The cause specific survival for these patients was 56% at 5 years and 40% at 10 years. Survival was significantly better for patients treated by CMT (88% at 5 years) as compared to XRT alone (40% at 5 years, P = 0.03) and for age less than 60 (72% at 5 years) compared to greater than or equal to 60 (30% at 5 years, P = 0.018). Relapse-free rate was 27% at 5 years with XRT alone and 89% with CMT (P = 0.01). Risk factors for loco-regional relapse (seven cases) included: large tumour bulk, treatment by XRT alone and use of 'limited' radiation fields. No radiation dose-response relationship could be identified in this study. Long term local control and survival for localised lymphoma of bone were excellent after treatment by CMT but XRT alone was associated with unacceptably high local and distant failure rates.
PURPOSE: This study was designed to determine the proportion of patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) managed with surveillance after orchidectomy who have more advanced disease and, therefore, require further treatment, the time to progression, the sites of progression, and the efficacy of treatment delayed until progression was recognized. PATIENTS AND METHODS: One hundred five patients were observed prospectively without further treatment after orchidectomy and full clinical staging. Treatment was given immediately upon detection of marker-positive, clinical, or radiologic evidence of disease. RESULTS: Thirty-seven patients (35.2%) have required further therapy for disease progression, occurring from 2 to 21 months after diagnosis. Thirty-six patients have been successfully treated. Overall, 104 patients (99%) remain alive and free of disease at 12 to 121 months after orchidectomy. Progression occurred in the retroperitoneum in 25 of 37 patients who developed further disease on surveillance. The presence of vascular invasion in the primary tumor was predictive of an increased risk of progression. CONCLUSION: Surveillance is a valid alternative to immediate retroperitoneal lymph node dissection in patients with clinical stage I NSGCTT but should be recommended only under the close supervision of physicians experienced in the diagnosis and treatment of testicular cancer.
The advantage of radical radiation therapy is that a proportion of patients will be cured while preserving normal bladder and sexual function. In most solid tumors, radiation therapy results in a local control rate inferior to that obtained by surgery, and this is also true in bladder cancer. Thus, efforts to preserve bladder function are likely to result in a lower local control rate than that achieved by cystectomy, and even if XRT achieved a 100% response rate, it cannot be expected to eliminate the risk of new tumor formation. Because cystectomy results in the loss of normal urinary bladder function and has only limited ability to cure, radiation remains an important therapeutic option in patients with bladder cancer. However, the question of whether radiation with an option of cystectomy for salvage would yield results comparable to those obtained by cystectomy has not been adequately answered. Most radiation oncologists agree that the use of radical radiation in patients with little or no chance of local control is inappropriate. Therefore, attempts at selection of responders, based on either clinical or biologic pretreatment parameters, are being investigated. Radical radiation therapy currently achieves a 50% complete response rate; thus, a large number of patients are potentially subjected to the morbidity of both modalities. Patients who have a small chance of achieving local control with XRT or who are known to be at risk for the rapid development of further bladder tumors (therefore unlikely to preserve their bladder for a significant time) are better served by primary cystectomy. Some patients prefer surgical treatment because it is decisive and quick; any attempts at bladder preservation potentially result in a lengthy treatment. Ideally, bladder sparing with XRT should be reserved for patients who are motivated to preserve normal bladder function and, therefore, patients should be involved in the decision regarding the choice of primary management. Although most patients embrace the opportunity for bladder preservation, they are frequently dissuaded from radiotherapy by the poor prospect of achieving local control and the risks of late complications.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinoma of the bladder is commonly treated for cure with external beam radiation. Whilst short-term results are associated with a good chance of disease control there is little information about the long-term results of such therapy. We present a retrospective review of the Princess Margaret Hospital experience in treating transitional cell carcinoma of the bladder and emphasis on the long-term follow-up of patients treated with radiotherapy (XRT). Between 1972 and 1980, 355 patients were treated with a radical course of external beam radiation. The overall survival was 20% at 10 years and the cause-specific survival was 32%. Radiation treatment resulted in a long-term bladder preservation in at least 25% of patients. The majority of long-term survivors without evidence of relapse were patients with T1 (solitary tumours), T2 and T3a tumours. This subgroup represents patients with disease favourable for treatment with radiation. Factors affecting response to the XRT and survival included T stage and tumour bulk. Radiation complications were frequent and were usually associated with local disease recurrence.
We have assessed the tumour markers placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD), and human chorionic gonadotrophin (beta HCG) using 2,000 serum samples from 286 patients with seminoma. The ROC curves show that no one marker performs adequately for the detection of disease either at initial staging or during follow-up. We used a Markov model heuristically to devise strategies, in which marker results were assessed in combination, which might be useful in clinical practice. We found that the best strategy was to consider a test result abnormal only if either the beta HCG was greater than 6 Ul-1 or the LD was greater than 400 U l-1 and the PLAP level was greater than 60 U l-1. This will detect about 50% of patients with disease and the false-positive rate is 2%. In practical terms this means that PLAP need only be estimated in patients whose beta HCG is less than 6 IU l-1 and whose LD is greater than 400 U l-1.
The usefulness of placental alkaline phosphatase (PLAP) as a tumour marker was assessed in 1578 serum samples from 236 patients with seminoma. Smoking habits were known for all but 7 patients (22 samples). Smoking was associated with significantly higher mean levels of PLAP in disease-free patients (28.8 [S.E. 2.1] U/l vs. 15.9 [1.3] U/l in non-smokers). Mean PLAP levels were higher in patients with active disease (78.6 [23.5] U/l in non-smokers and 47.2 [18.5] U/l in smokers). The median values showed a similar trend. However, there was considerable overlap between the various groups and differences between mean and median values indicated that PLAP values were distributed asymmetrically. The predictive value of PLAP as a tumour marker was consequently much less than superficial inspection of these values might suggest. In 97 patients on surveillance, only 2 out of 11 patients who relapsed had elevated PLAP at the time of clinically detectable relapse. With the upper limit of normal PLAP quoted by our laboratory (35 U/l), specificity and sensitivity were, respectively, 88% and 45% (all patients) and 96% and 47% (non-smokers). The sensitivity and specificity of PLAP were assessed in more detail for a series of threshold values (normal vs. abnormal) with a graphical method. Only in non-smokers did PLAP seem useful and even in this group the positive predictive value of an "abnormal" test may be low; less than 50% in clinically relevant circumstances. Serum PLAP assay cannot usefully stand alone as a marker for seminoma and its routine estimation contributes little to follow-up.
One hundred thirteen patients with localized gastrointestinal lymphoma treated by surgery and postoperative irradiation between 1967 and 1985 were reviewed. At 15 years, actuarial survival of this group was 40.6%, with a cause-specific survival of 69.2% and a relapse-free rate of 64%. Two-thirds of relapses occurred at distant sites. In Stage IA and IIA patients with no residuum or with positive resection margins, (N = 90) only site of involvement and stage predicted for relapse. Age, histologic subtype group, and depth of bowel wall invasion did not affect relapse risk. In the very favorable group (Stage IA, IIA, no residuum or microscopic residuum), 8.4% of patients with stomach lymphoma relapsed compared to 25% of patients with small bowel lymphoma. The risk of early relapse was higher in those with Stage IIA small bowel lymphoma than those with Stage IA small bowel lymphoma. We continue to recommend adjuvant abdominal irradiation for patients with Stage IA, IIA completely resected stomach lymphoma and Stage IA completely resected small bowel lymphoma. We recommend combined modality therapy for patients with completely resected Stage IIA small bowel lymphoma and all other localized gastrointestinal lymphoma where visible residual disease is present.
A study of post-orchiectomy surveillance without radiation therapy was done in patients with histologically pure seminoma apparently confined to the testicle. Criteria for study entry included a negative physical examination, chest x-ray, bipedal lymphogram, excretory urogram, abdomino-pelvic computerized tomography scan and serum alpha-fetoprotein. Followup consisted of frequent clinical examination, repeat lymphograms, abdominal computerized tomography scans, chest x-rays and serum markers. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases beyond the testicle, sites of relapse, factors predictive of relapse, and over-all cure rate and treatment morbidity. Of 81 patients followed for 3 to 43 months (median 19 months) only 3 had relapse at 3, 5 and 18 months after orchiectomy with nonbulky retroperitoneal disease: 1 patient had disease 17 months after salvage infradiaphragmatic radiation therapy, 1 had an increase in beta-human chorionic gonadotropin 11 months after radiation therapy, presumably due to occult nonseminoma, and he is receiving chemotherapy, and 1 has not yet completed treatment. Further followup is necessary to determine ultimate survival, since a risk for later relapse exists. However, to date it does not appear as if the outcome has been compromised when surveillance was applied in place of routine adjuvant radiotherapy.
Patients with muscle invasive carcinoma of the bladder treated with radical radiation were prospectively documented and followed in an attempt to identify prognostic factors predictive of the response to treatment. Data on 121 consecutive patients treated with radical radiation between 1981 and 1985 are presented. Over-all actuarial survival of the patient population (median age 70 years) was 31.6% at 5 years and cause-specific survival was 44.8%. At analysis 33 of 121 patients (27.3%) were alive with preserved bladder function. Independent prognostic factors for cause-specific survival and for complete response with radical radiation were tumor configuration, hemoglobin level and clinical stage. The rate free of local relapse was significantly influenced by stage and presence of coexistent carcinoma in situ. The study suggests that factors other than stage and grade influence prognosis in invasive bladder cancer and should be considered in interpreting treatment results.
We report the experience from 13 Canadian radiotherapy centres concerning the treatment and outcome for 1074 papillary and 504 follicular thyroid cancer patients followed for 4-24 years. Surgical resection was carried out in almost all patients; there was no correlation between the type of operation and recurrence or survival. Treatment with external irradiation (201 patients) radioiodine (214 patients), or both (107 patients) was used more often in poor prognosis patients than in those with good prognostic factors, and was effective in reducing local recurrences and improving survival, especially in patients with microscopic residual disease postoperatively. Treatment complications were common but rarely fatal. Thyroid cancer was the cause of death in over half of the papillary cancer deaths and in two-thirds of the follicular cancer deaths.
The principal morbidity of retroperitoneal lymphadenectomy is the potential loss of ejaculation and, therefore, fertility owing to damage of the retroperitoneal sympathetic nerves that form the superior hypogastric plexus. We describe the results of our retroperitoneal lymphadenectomy when individual nerves from the sympathetic ganglia are identified and preserved while still performing a thorough bilateral retroperitoneal lymphadenectomy. The nerve-sparing procedure was technically feasible in 20 of 30 consecutive patients and it was only impractical with extensive gross disease. Of the 20 patients 18 (90 per cent) ejaculate, including 8 with bulky (5 cm. or more) residual retroperitoneal disease who underwent a successful nerve-sparing operation. All 12 patients (100 per cent) with nonbulky disease ejaculate. With short followup, no retroperitoneal recurrences have been detected. This technique is an alternative to limited dissection designed to spare nerves using boundaries based on the patterns of metastatic involvement.
The role of surgery in the management of patients with primary lymphoma of the thyroid gland has been addressed after review of 61 patients treated at Princess Margaret Hospital between 1958 and August 1982, 46 of whom had clinical stage I and II disease confined to the thyroid gland or lymph nodes or both above the diaphragm. Postoperative radiation therapy was used in 34 patients, radiation therapy and chemotherapy in 11 patients, and chemotherapy alone in 1 patient. Analysis of disease progression, local relapse, and distant disease recurrence indicated that postoperative residual disease bulk predicted strongly for both local and distant disease progression. Overall cause-specific survival was 59% at 5 years, with a relapse-free rate of 46% at 5 years. Of those with less than 2.5 cm of residual disease after surgery, 80% achieved lifelong local disease control compared with 40% for those with residual disease in excess of 2.5 cm after surgery. Distant relapse rates were 7% and 23% for those with less than 2.5 cm and greater than 2.5 cm after surgery, respectively. The long-term survival rate for those with disease progression during this period was approximately 10%, with a median survival expectancy of 18 months. It is suggested that those patients without an antecedent cytologically based diagnosis of lymphoma undergo biopsy and removal of operable tumor without compromise of parathyroid glands, recurrent laryngeal nerves, or appearance. Those patients with an existing cytologic diagnosis of lymphoma and bulky and/or inoperable tumor may be more effectively managed with a combined chemotherapy-radiation therapy program.
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This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.