Testicular function was studied in three groups of patients previously treated for malignant dise... more Testicular function was studied in three groups of patients previously treated for malignant disease, and a control group of adult males. The adult patients in groups one and two underwent unilateral orchidectomy for a testicular tumour but only in group two was this followed by post-operative high-dose irradiation (30 Gy) to the remaining testis. Four of the five boys in group three had a unilateral orchidectomy between the ages of 1 and 4 years and all five received a similar dose of irradiation (27·5–30 Gy) to the scrotum as in group two. The five subjects in group three were studied between the ages of 12 and 34 years. In group one the median basal testosterone level (16·0 nmol/l) was normal and the basal gonadotrophin levels mildly but significantly increased, reflecting a resetting of the pituitary-testicular axis following unilateral orchidectomy. In group two the median basal testosterone level (12·5 nmol/l) was significantly lower and the median basal FSH and LH levels were...
2 Lichtman MA, Vaughan JH, Hames CG. The distribution of immunoglobulins, anti-gamma-G globulins ... more 2 Lichtman MA, Vaughan JH, Hames CG. The distribution of immunoglobulins, anti-gamma-G globulins ("rheumatoid factors") and antinuclear antibodies in white and Negro subjects in Evans County, Georgia. Arthritis Rheum 1967;lO: 204-15. 3 McGregor IA, Gilles HM. Studies on the significance of high serum gammaglobulin concentrations in Gambian Africans. II. Gamma-globulin concentrations of Gambian children in the fourth, fifth and sixth years of life.
ONCOLOGY AND CHEMOTHERAPY nodes were found in only 20 per cent of all cases. Salvage cystectomy f... more ONCOLOGY AND CHEMOTHERAPY nodes were found in only 20 per cent of all cases. Salvage cystectomy for local recurrence after radical radiotherapy produced a 60 per cent 5-year survival rate in 18 well selected patients. Salvage cystectomy usually was performed within 18 months after the completion of radiotherapy. The authors conclude that preoperative radiotherapy and cystectomy are the current treatments of choice for patients with deeply invasive bladder carcinoma who are ~65 years old and especially for men. For older patients and for women, radical radiotherapy alone is advised, with salvage cystectomy reserved for selected patients with local recurrences.
In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal... more In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal adenopathy at presentation or after a period of surveillance were treated. Complete radiological resolution of disease was obtained in 34 patients and a residual mass remained in 26, the remainder having progression of the para-aortic or other metastatic disease. There was no para-aortic relapse in 47 patients receiving radiotherapy post-chemotherapy whereas 2/11 who did not receive radiotherapy or an immediate retroperitoneal node dissection relapsed. Morbidity from radiotherapy was minimal apart from subcutaneous fibrosis in the irradiated area of 6 patients. It is concluded that radiotherapy is effective in sterilising minimal residual tumour post-chemotherapy and may be considered as an alternative to surgery.
Predicting late rectal complications following prostate conformal radiotherapy using biologically effective doses and normalized dose-surface histograms
The British journal of radiology, 1997
A model to predict the late normal tissue complication probability (NTCP) of the rectum following... more A model to predict the late normal tissue complication probability (NTCP) of the rectum following conformal therapy is described. The model evaluates the biological consequence of inhomogeneities in the physical dose by computing dose histograms of the biologically effective dose to the surface of the rectum for a given fractionation scheme. A method of normalizing the surface area of the rectum is employed so that the predicted NTCP is independent of the differing cross-sectional size of sections of the rectum, ensuring the NTCP is dependent only on the dose delivered to sensitive rectal tissues. The model has been used to assess severe late rectal complications and the milder RTOG grades 2 and 3 reactions. This model was found to predict severe toxicity levels of 1.7 +/- 0.6% for an accelerated treatment of 50 Gy in 16 fractions commonly employed at this centre. This result lies between the severe toxicities predicted for 60 and 62 Gy delivered in 2 Gy fractions. The model predict...
Metachroneus appearance of bilateral germ cell tumours despite chemotherapy
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 1985
Histopathology in the Prediction of Relapse of Patients with Stage I Testicular Teratoma Treated by Orchidectomy Alone
The Lancet, 1987
259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orch... more 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.
A case of signet ring cell lymphoma, the eighth in published reports is recorded. This rare tumou... more A case of signet ring cell lymphoma, the eighth in published reports is recorded. This rare tumour is a variant of follicular lymphoma which may be mistaken for metastatic carcinoma. The case has been studied by light microscopy, immunohistochemistry and electron microscopy and confirms that this subgroup has rather uniform characteristics. Observations on the possible origins of the vacuoles are presented.
Short course para-aortic radiation for stage I seminoma of the testis
International Journal of Radiation Oncology*Biology*Physics, 2003
To determine the outcome in men with Stage I seminoma treated with low-dose para-aortic radiation... more To determine the outcome in men with Stage I seminoma treated with low-dose para-aortic radiation. Between January 1988 and December 2000, 431 men with Stage I seminoma were treated with para-aortic radiation to a midplane dose of 20 Gy in 8 fractions over 10 days. At a median follow-up of 62 months, 15 patients (3.5%) had relapsed, with a median time to relapse of 13 months (range: 9 to 39 months). Nine patients had pelvic nodal relapse; in addition, 1 patient had para-aortic involvement, and 2 had distant disease. Four had metastatic disease only (mediastinum 2, lung 2). One patient had scrotal recurrence, and 1 was treated for progressive rise in human chorionic gonadotrophin without identifiable disease. Initial treatment at relapse was chemotherapy (12), radiation (2), and surgery (1). One patient died from progressive disease. Thirteen men (3%) have developed second malignancies, including 7 contralateral testicular tumors, 5 solid malignancies, and 1 leukemia. The overall 5-year survival was 98%, and the estimated recurrence-free survival at 5 years was 96.3%. On log-rank univariate analysis, lymphovascular invasion, involvement of the tunica, and a preoperative human chorionic gonadotrophin level of greater than 5 were found to be of prognostic significance for recurrence. These data support short-duration, limited-field radiation as an optimal safe and effective protocol in the management of Stage I seminoma patients.
Bladder movement during radiation therapy for bladder cancer: Implications for treatment planning
International Journal of Radiation Oncology*Biology*Physics, 1997
To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to id... more To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to identify factors that predict for excessive alterations in bladder position. To use the above information to assist in defining the "adequate" planning target volume margin. Thirty patients with bladder cancer suitable for radical courses of RT were followed prospectively. Patients had an initial planning computerized tomography (CT) scan of the pelvis and three subsequent scans performed weekly during the treatment period. The following measurements were made on each scan in the midbladder slice: maximum anteroposterior (AP) and lateral bladder dimensions, AP rectal diameter, and the distance (margin) between the bladder walls (anterior, posterior, right, and left lateral) and the 95% isodose line. Various patient and tumor data, including bladder and bowel symptoms, were recorded to attempt correlation with bladder movement. Bladder size: the median bladder size (area) over all scans in all patients was 36.9 cm2 (range: 16.2 to 80.9 cm2). The change in bladder area across each sequence varied from 3.3 to 29.1 cm2 (7-55% change in area between scans). Patients with bladders of larger than the median size on the planning scan (despite emptying) were more likely to have alteration in size than those with small bladders, and this change was in the direction of contraction (p = 0.01). Bladder displacement: bladder wall movement of > 1.5 cm was defined as "significant." Eighteen of 30 patients (60%) demonstrated "significant" movement of at least one bladder wall relative to the original isodose plot. Movement resulting in margin reduction occurred in 10 patients (33%). Two patients required treatment replanning due to consistently altered bladder position. There was no pattern to displacement through RT, and all walls were at approximately equal risk of movement. Factors influencing bladder movement: posterior bladder wall movement appeared to relate to "marked" (>2 cm) rectal diameter change. There was a trend for patients with larger amounts of residual bladder tumor (greater than the median) to exhibit more bladder movement; 11 of 14 "moved" compared with 7 of 16 patients with less residual tumor. Other clinical factors including age, sex, body size, acute RT reaction, and tumor stage did not appear to relate to bladder movement. Bladder movement during RT is clinically relevant and is random with respect to both time and direction. We recommend, at least with respect to tumor-bearing regions of the bladder, that no less than a 2.0 cm margin should be allowed.
Clinical variability of target volume description in conformal radiotherapy planning
International Journal of Radiation Oncology*Biology*Physics, 1998
The pivotal step in radiation planning is delineation of the target volume and production of a tr... more The pivotal step in radiation planning is delineation of the target volume and production of a treatment plan to encompass this. This study assesses the variation of physicians in creation of these volumes. Three radiologists and eight radiation oncologists outlined the gross tumour volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In addition, the radiation oncologists (RO) created a planning target volume according to a set protocol for all cases. Volumes were produced and comparison of these volumes and the position of the isocenters were analysed. In addition, the margins allowed were measured and compared. There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p = 0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from 1.25 to 3.33. There was no significant difference in mean PTV values between the two groups of ROs divided by specialization in uro-oncology. The mean variation in location of the isocenter from the centroid of the radiologists' volume in the four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm. Minimum margins allowed in each case varied from minus 7 mm to 9 mm. This study demonstrates significant interphysician variability in producing target volumes and radiation plans for conformal radiotherapy. The scale of this difference is clearly of significance, with up to 3-fold variation in volumes delineated by clinicians. The factors leading to these differences will be further addressed. The existence of such variability, however, clearly needs to be accepted as a factor in the overall uncertainty analysis in conformal radiotherapy planning.
International Journal of Radiation Oncology*Biology*Physics, 1996
A previous study of internal organ motion (1). in which a group of twelve patients with prostate ... more A previous study of internal organ motion (1). in which a group of twelve patients with prostate cancer received CT scans on different days, showed variations in the position of the prostate and seminal vesicles, with larger variations observed in the latter. In addition, prostate and seminal vesicle positions were observed to be significantly correlated with changes in bladder volume. For most of the patients in the study the amount of bladder tilling prior to scanning was not controlled, and large variations in bladder volume were observed for some patients. In light of these results, a second study in a larger group of patients has been undertaken, to examine the variability in the position of the prostate and nearby organs when the amount of bladder filling is controlled.
Testicular function was studied in three groups of patients previously treated for malignant dise... more Testicular function was studied in three groups of patients previously treated for malignant disease, and a control group of adult males. The adult patients in groups one and two underwent unilateral orchidectomy for a testicular tumour but only in group two was this followed by post-operative high-dose irradiation (30 Gy) to the remaining testis. Four of the five boys in group three had a unilateral orchidectomy between the ages of 1 and 4 years and all five received a similar dose of irradiation (27·5–30 Gy) to the scrotum as in group two. The five subjects in group three were studied between the ages of 12 and 34 years. In group one the median basal testosterone level (16·0 nmol/l) was normal and the basal gonadotrophin levels mildly but significantly increased, reflecting a resetting of the pituitary-testicular axis following unilateral orchidectomy. In group two the median basal testosterone level (12·5 nmol/l) was significantly lower and the median basal FSH and LH levels were...
2 Lichtman MA, Vaughan JH, Hames CG. The distribution of immunoglobulins, anti-gamma-G globulins ... more 2 Lichtman MA, Vaughan JH, Hames CG. The distribution of immunoglobulins, anti-gamma-G globulins ("rheumatoid factors") and antinuclear antibodies in white and Negro subjects in Evans County, Georgia. Arthritis Rheum 1967;lO: 204-15. 3 McGregor IA, Gilles HM. Studies on the significance of high serum gammaglobulin concentrations in Gambian Africans. II. Gamma-globulin concentrations of Gambian children in the fourth, fifth and sixth years of life.
ONCOLOGY AND CHEMOTHERAPY nodes were found in only 20 per cent of all cases. Salvage cystectomy f... more ONCOLOGY AND CHEMOTHERAPY nodes were found in only 20 per cent of all cases. Salvage cystectomy for local recurrence after radical radiotherapy produced a 60 per cent 5-year survival rate in 18 well selected patients. Salvage cystectomy usually was performed within 18 months after the completion of radiotherapy. The authors conclude that preoperative radiotherapy and cystectomy are the current treatments of choice for patients with deeply invasive bladder carcinoma who are ~65 years old and especially for men. For older patients and for women, radical radiotherapy alone is advised, with salvage cystectomy reserved for selected patients with local recurrences.
In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal... more In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal adenopathy at presentation or after a period of surveillance were treated. Complete radiological resolution of disease was obtained in 34 patients and a residual mass remained in 26, the remainder having progression of the para-aortic or other metastatic disease. There was no para-aortic relapse in 47 patients receiving radiotherapy post-chemotherapy whereas 2/11 who did not receive radiotherapy or an immediate retroperitoneal node dissection relapsed. Morbidity from radiotherapy was minimal apart from subcutaneous fibrosis in the irradiated area of 6 patients. It is concluded that radiotherapy is effective in sterilising minimal residual tumour post-chemotherapy and may be considered as an alternative to surgery.
Predicting late rectal complications following prostate conformal radiotherapy using biologically effective doses and normalized dose-surface histograms
The British journal of radiology, 1997
A model to predict the late normal tissue complication probability (NTCP) of the rectum following... more A model to predict the late normal tissue complication probability (NTCP) of the rectum following conformal therapy is described. The model evaluates the biological consequence of inhomogeneities in the physical dose by computing dose histograms of the biologically effective dose to the surface of the rectum for a given fractionation scheme. A method of normalizing the surface area of the rectum is employed so that the predicted NTCP is independent of the differing cross-sectional size of sections of the rectum, ensuring the NTCP is dependent only on the dose delivered to sensitive rectal tissues. The model has been used to assess severe late rectal complications and the milder RTOG grades 2 and 3 reactions. This model was found to predict severe toxicity levels of 1.7 +/- 0.6% for an accelerated treatment of 50 Gy in 16 fractions commonly employed at this centre. This result lies between the severe toxicities predicted for 60 and 62 Gy delivered in 2 Gy fractions. The model predict...
Metachroneus appearance of bilateral germ cell tumours despite chemotherapy
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 1985
Histopathology in the Prediction of Relapse of Patients with Stage I Testicular Teratoma Treated by Orchidectomy Alone
The Lancet, 1987
259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orch... more 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.
A case of signet ring cell lymphoma, the eighth in published reports is recorded. This rare tumou... more A case of signet ring cell lymphoma, the eighth in published reports is recorded. This rare tumour is a variant of follicular lymphoma which may be mistaken for metastatic carcinoma. The case has been studied by light microscopy, immunohistochemistry and electron microscopy and confirms that this subgroup has rather uniform characteristics. Observations on the possible origins of the vacuoles are presented.
Short course para-aortic radiation for stage I seminoma of the testis
International Journal of Radiation Oncology*Biology*Physics, 2003
To determine the outcome in men with Stage I seminoma treated with low-dose para-aortic radiation... more To determine the outcome in men with Stage I seminoma treated with low-dose para-aortic radiation. Between January 1988 and December 2000, 431 men with Stage I seminoma were treated with para-aortic radiation to a midplane dose of 20 Gy in 8 fractions over 10 days. At a median follow-up of 62 months, 15 patients (3.5%) had relapsed, with a median time to relapse of 13 months (range: 9 to 39 months). Nine patients had pelvic nodal relapse; in addition, 1 patient had para-aortic involvement, and 2 had distant disease. Four had metastatic disease only (mediastinum 2, lung 2). One patient had scrotal recurrence, and 1 was treated for progressive rise in human chorionic gonadotrophin without identifiable disease. Initial treatment at relapse was chemotherapy (12), radiation (2), and surgery (1). One patient died from progressive disease. Thirteen men (3%) have developed second malignancies, including 7 contralateral testicular tumors, 5 solid malignancies, and 1 leukemia. The overall 5-year survival was 98%, and the estimated recurrence-free survival at 5 years was 96.3%. On log-rank univariate analysis, lymphovascular invasion, involvement of the tunica, and a preoperative human chorionic gonadotrophin level of greater than 5 were found to be of prognostic significance for recurrence. These data support short-duration, limited-field radiation as an optimal safe and effective protocol in the management of Stage I seminoma patients.
Bladder movement during radiation therapy for bladder cancer: Implications for treatment planning
International Journal of Radiation Oncology*Biology*Physics, 1997
To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to id... more To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to identify factors that predict for excessive alterations in bladder position. To use the above information to assist in defining the "adequate" planning target volume margin. Thirty patients with bladder cancer suitable for radical courses of RT were followed prospectively. Patients had an initial planning computerized tomography (CT) scan of the pelvis and three subsequent scans performed weekly during the treatment period. The following measurements were made on each scan in the midbladder slice: maximum anteroposterior (AP) and lateral bladder dimensions, AP rectal diameter, and the distance (margin) between the bladder walls (anterior, posterior, right, and left lateral) and the 95% isodose line. Various patient and tumor data, including bladder and bowel symptoms, were recorded to attempt correlation with bladder movement. Bladder size: the median bladder size (area) over all scans in all patients was 36.9 cm2 (range: 16.2 to 80.9 cm2). The change in bladder area across each sequence varied from 3.3 to 29.1 cm2 (7-55% change in area between scans). Patients with bladders of larger than the median size on the planning scan (despite emptying) were more likely to have alteration in size than those with small bladders, and this change was in the direction of contraction (p = 0.01). Bladder displacement: bladder wall movement of > 1.5 cm was defined as "significant." Eighteen of 30 patients (60%) demonstrated "significant" movement of at least one bladder wall relative to the original isodose plot. Movement resulting in margin reduction occurred in 10 patients (33%). Two patients required treatment replanning due to consistently altered bladder position. There was no pattern to displacement through RT, and all walls were at approximately equal risk of movement. Factors influencing bladder movement: posterior bladder wall movement appeared to relate to "marked" (>2 cm) rectal diameter change. There was a trend for patients with larger amounts of residual bladder tumor (greater than the median) to exhibit more bladder movement; 11 of 14 "moved" compared with 7 of 16 patients with less residual tumor. Other clinical factors including age, sex, body size, acute RT reaction, and tumor stage did not appear to relate to bladder movement. Bladder movement during RT is clinically relevant and is random with respect to both time and direction. We recommend, at least with respect to tumor-bearing regions of the bladder, that no less than a 2.0 cm margin should be allowed.
Clinical variability of target volume description in conformal radiotherapy planning
International Journal of Radiation Oncology*Biology*Physics, 1998
The pivotal step in radiation planning is delineation of the target volume and production of a tr... more The pivotal step in radiation planning is delineation of the target volume and production of a treatment plan to encompass this. This study assesses the variation of physicians in creation of these volumes. Three radiologists and eight radiation oncologists outlined the gross tumour volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In addition, the radiation oncologists (RO) created a planning target volume according to a set protocol for all cases. Volumes were produced and comparison of these volumes and the position of the isocenters were analysed. In addition, the margins allowed were measured and compared. There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p = 0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from 1.25 to 3.33. There was no significant difference in mean PTV values between the two groups of ROs divided by specialization in uro-oncology. The mean variation in location of the isocenter from the centroid of the radiologists' volume in the four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm. Minimum margins allowed in each case varied from minus 7 mm to 9 mm. This study demonstrates significant interphysician variability in producing target volumes and radiation plans for conformal radiotherapy. The scale of this difference is clearly of significance, with up to 3-fold variation in volumes delineated by clinicians. The factors leading to these differences will be further addressed. The existence of such variability, however, clearly needs to be accepted as a factor in the overall uncertainty analysis in conformal radiotherapy planning.
International Journal of Radiation Oncology*Biology*Physics, 1996
A previous study of internal organ motion (1). in which a group of twelve patients with prostate ... more A previous study of internal organ motion (1). in which a group of twelve patients with prostate cancer received CT scans on different days, showed variations in the position of the prostate and seminal vesicles, with larger variations observed in the latter. In addition, prostate and seminal vesicle positions were observed to be significantly correlated with changes in bladder volume. For most of the patients in the study the amount of bladder tilling prior to scanning was not controlled, and large variations in bladder volume were observed for some patients. In light of these results, a second study in a larger group of patients has been undertaken, to examine the variability in the position of the prostate and nearby organs when the amount of bladder filling is controlled.
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