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Objective: To examine the impact of granulocyte-colony stimulating factor (G-CSF) use on the incidence and severity of bleomycin-induced pneumonitis (BIP) in patients with germ cell tumor (GCT) receiving first-line chemotherapy., Patients and Methods: Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy, and medical records. All patients receiving first line chemotherapy between January 1, 2000 and December 31, 2010 were included. Patients receiving at least 1 dose of G-CSF were identified. BIP was graded using Common Terminology Criteria for Adverse Events criteria. Logistic regression was used to explore predictors for risk and severity of BIP. Statistical significance was defined as P < .05., Results: Data on 212 patients with GCT treated with a bleomycin-containing chemotherapy regimen were available. The median age was 31 years. The median follow-up period was 36.7 months. BIP occurred in 73 patients (34%), a majority (n = 55) of which were asymptomatic events (Common Terminology Criteria for Adverse Events, grade 1). G-CSF use was not associated with increased risk of BIP in multivariable analyses (odds ratio, 1.60; P = .13), nor was it associated with increased severity of symptomatic BIP (on average 1.22 grades higher; P = .09). There was a non-statistically significant trend towards greater risk of BIP in patients that developed renal impairment during chemotherapy treatment (odds ratio, 2.56; P = .053)., Conclusion: In patients with GCT receiving first line chemotherapy, G-CSF use is not associated with an increased risk of BIP. Furthermore, the use of G-CSF did not have any significant effect on the severity of BIP events. Clinicians are reminded to be vigilant of patients that develop renal impairment while undergoing chemotherapy treatment, given the greater risk of BIP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Cisplatin-based chemotherapy, a mainstay of treatment for disseminated germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many patients with disseminated GCTs have large retroperitoneal lymph node (RPLN) metastases that may cause venous stasis and increase the risk of VTE development. We hypothesized that there was an association between large RPLN and chemotherapy-associated VTE risk., Patients and Methods: The training cohort was composed of patients with disseminated GCT receiving first-line chemotherapy at Princess Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was defined as more than 5 cm in maximal axial diameter. The predictive and discriminatory accuracies of a model using large RPLN in predicting VTE were compared with high-risk Khorana score (≥ 3) using logistic regression and area under receiver operator characteristic curves (AUROCs). The model was externally validated in a cohort of patients treated at the London Health Sciences Centre., Results: The training cohort comprised 216 patients, 21 (10%) of whom developed VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR], 5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor-risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR, 4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory accuracy of large RPLN over high-risk Khorana score was validated in the London cohort (AUROC, 0.61 v 0.57, respectively)., Conclusion: Large RPLN is associated with VTE in patients with disseminated GCT and provides higher discriminatory accuracy than high-risk Khorana score. Results should be validated in larger, prospective studies. Prophylactic anticoagulation may be considered in high-risk patients., (© 2015 by American Society of Clinical Oncology.)

Background: Since 1981 Princess Margaret Hospital has used initial active surveillance (AS) with delayed treatment at relapse as the preferred management for all patients with clinical stage I nonseminomatous germ cell tumors (NSGCT)., Objective: Our aim was to report our overall AS experience and compare outcomes over different periods using this non-risk-adapted approach., Design, Setting, and Participants: Three hundred and seventy-one patients with stage I NSGCT were managed by AS from 1981 to 2005. For analysis by time period, patients were divided into two cohorts by diagnosis date: initial cohort, 1981-1992 (n=157), and recent cohort, 1993-2005 (n=214)., Intervention: Patients were followed at regular intervals, and treatment was only given for relapse., Measurements: Recurrence rates, time to relapse, risk factors for recurrence, disease-specific survival, and overall survival were determined., Results and Limitations: With a median follow-up of 6.3 yr, 104 patients (28%) relapsed: 53 of 157 (33.8%) in the initial group and 51 of 214 (23.8%) in the recent group. Median time to relapse was 7 mo. Lymphovascular invasion (p<0.0001) and pure embryonal carcinoma (p=0.02) were independent predictors of recurrence; 125 patients (33.7%) were designated as high risk based on the presence of one or both factors. In the initial cohort, 66 of 157 patients (42.0%) were high risk and 36 of 66 patients (54.5%) relapsed versus 17 of 91 low-risk patients (18.7%) (p<0.0001). In the recent cohort, 59 of 214 patients (27.6%) were high risk and 29 of 59 had a recurrence (49.2%) versus 22 of 155 low-risk patients (14.2%) (p<0.0001). Three patients (0.8%) died from testis cancer. The estimated 5-yr disease-specific survival was 99.3% in the initial group and 98.9% in the recent one., Conclusions: Non-risk-adapted surveillance is an effective, simple strategy for the management of all stage I NSGCT., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: After orchidectomy, the standard management options available for stage I seminoma are surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. The optimal follow-up protocol for surveillance is yet to be determined but includes frequent chest radiography (CXR) and computed tomography (CT) scan of the abdomen and pelvis (CT-AP)., Objective: The purpose of this study was to identify the modality that first detected relapse and to assess the value of the CXR in this setting., Design, Setting, and Participants: Five hundred twenty-seven patients with histologically confirmed stage I testicular seminoma were managed with surveillance at our institution between 1982 and 2005. Routine CXRs were performed with each CT-AP and were done every 4-6 mo for 7 yr and annually thereafter. The median follow-up was 72 mo (range: 1-193)., Measurements: Measurements included the 5-yr relapse rate, overall survival, and disease-free survival to determine the modality that first detected relapse disease., Results and Limitations: The 5-yr actuarial relapse rate for the 527 patients was 14%. The 5-yr disease-free survival and overall survival were 85.7% and 98.6%, respectively. Seventy-three patients (97.3%) had an abnormal CT-AP and a normal CXR at relapse. One patient (1.3%) had an abnormal CT-AP with pulmonary metastasis on CXR and CT chest scan, and one patient (1.3%) had a biopsy-proven inguinal node metastasis with a normal CXR. No patient had a normal CT-AP or physical examination with an abnormal CXR at relapse. This is a single-center retrospective study based on a relatively small number of relapses and may be subject to bias. Confirmation of these results from other studies would be useful for wider clinical applicability., Conclusions: All except one relapse were detected by CT-AP with no relapses detected on CXR alone; therefore, CXR may be omitted as routine imaging in surveillance protocols., (2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To review treatment outcome and patterns of failure for patients with stage II testicular seminoma and to identify prognostic factors for relapse., Methods: From 1981 to 1999, 126 men with stage II seminoma were treated at Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for prognostic significance for subsequent relapse., Results: At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance., Conclusions: In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.

Purpose: Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution., Methods and Materials: Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (+/- contralateral) pelvic lymph nodes (dose: 25-35 Gy)., Results: With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged., Conclusions: Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only.

Malignant teratoma of the thyroid gland is exceedingly rare in adults. Many of the cases previously reported in the medical literature have fatal outcomes because of spread of tumor refractory to treatment. We report a case of primary malignant teratoma of the thyroid in a 37-year-old woman. She was treated successfully with a combination of surgery, postoperative cis-platinum-based chemotherapy and radiation therapy to the neck, with long-term follow-up (10 years). This case and the modern experience of combined modality therapy in extragonadal germ cell tumors of the thyroid and other sites illustrate that these tumors should be managed aggressively in order to achieve best results.

Introduction: Surveillance is an alternative to adjuvant radiotherapy for stage I testicular seminoma. We present the long-term results of seminoma surveillance, with emphasis on quantifying the risk of late relapse beyond 5 years., Methods: From 1981 to 1993, of 431 men with stage I testicular seminoma, 203 were managed by surveillance following radical orchidectomy. The surveillance protocol comprised a combination of clinical examination, CT scans of abdomen and pelvis, chest x-rays and serum markers, at defined intervals., Results: At a median follow-up of 9.2 years, 35 men have relapsed. Five of the relapses occurred more than 5 years after orchidectomy (at 5.1, 6.9, 7.3, 7.3, and 9.0 years). The actuarial risk of relapse at 5 and 10 years was 15% (standard error [SE] 1.1%) and 18% (SE 1.8%) respectively. One hundred sixty one men were free of relapse at 5 years, and have been followed beyond this point for a median of 4.3 years. The actuarial risk of relapse between 5 and 10 years was 4% (SE 0.5%)., Conclusions: These results demonstrate that there is a small but clinically significant risk of relapse more than 5 years after orchidectomy for stage I seminoma. These data support the need for long term surveillance.

Purpose: The benefits of recording the tumor, node, and metastasis (TNM) stages of cancer patients are well accepted, but little is known about how accurately this is performed. An audit was performed to determine the accuracy of recorded stage and to act as a baseline before the implementation of an education program., Patients and Methods: All new patient referrals to Princess Margaret Hospital between July 1 and August 31, 1997, were reviewed. An audit panel composed of five health record technicians (HRTs) and 10 doctors was assembled. Each auditor reviewed 10% of the health record. If there was a discrepancy between the stage in the health record and the auditor stage, then the final stage was determined by the audit committee. Analysis of the agreement between the health record, the physician auditor, the HRT auditor, and the final stage was performed., Results: A total of 855 patients were referred with a new diagnosis of a malignancy for which there was a TNM stage system; 833 patients (97.4%) had a stage assigned. There was agreement between the health record stage and final stage in 80% (95% confidence interval [CI], 77% to 82%) of cases for clinical stage, compared with 90% (95% CI, 87% to 92%) for pathologic stage. Of the major site groups, lung was the least accurately recorded. The most common major discrepancies were due to the recording of X when a definite category could be assigned., Conclusion: This audit demonstrates the importance of staging and provides impetus to develop staging guidelines and education programs.

Purpose: To validate the use of surveillance as an alternative to adjuvant RT in clinical stage I seminoma, we analyzed our experience with the two approaches in terms of long term outcome and cost., Patients and Methods: Between January 1981 and December 1994, 471 patients with stage I testicular seminoma were treated at our institution. Of these, 245 patients received post-operative RT (25 Gy) to the retroperitoneal lymph nodes, and 226 have been managed with surveillance following orchidectomy. Two patients were included in this series twice; both had RT previously for seminoma, were placed on surveillance for a contralateral seminoma and were analyzed for outcome of both primary tumors. The costs associated with both approaches were estimated in 1994 Canadian dollars (C$)., Results: With a median follow-up of 7.7 years in the surveillance patients, and 9.7 years in the adjuvant RT cohort, the 5 year actuarial survival for all patients was 97% and the cause-specific survival (CSS) was 99.8%. Of the 226 patients on surveillance 37 patients have relapsed to date; five of those developed a second relapse. One patient has died of disease. Of the 245 patients treated with adjuvant RT, 14 patients have relapsed and none had a second relapse. The CSS was 100%. Thirteen patients on surveillance (5.7%) and 10 patients treated with post-operative RT (4.1%) have received chemotherapy as part of their management. One hundred and eighty-nine patients on surveillance have received no post-orchidectomy treatment to date. Surveillance was more expensive with an average additional cost per patient per year of Can$2620 over 10 years., Conclusions: Both adjuvant RT and surveillance give excellent results in stage I seminoma. The documented increased risk of second malignant tumors following RT must be taken into account when considering the additional cost of surveillance. The routine use of post-operative RT in stage I seminoma should be reconsidered and a surveillance program offered to all patients as an alternative management option.

Combination high-dose cytosine arabinoside (ARA-C) and daunorubicin (DNR) for primary remission induction of patients with acute myeloblastic leukemia (AML) was evaluated in a single institution study. Patients aged 55 or less with an HLA-sibling received an allogeneic bone marrow transplant (alloBMT) in first remission; other responders were offered autologous BMT (autoBMT). For remission induction 93 patients aged less than 60 received DNR 45 mg/m(2) BSA x 3 and ARA-C 2 gm/m(2) BSA every 12 hours for 12 doses; 53 aged 60 or older DNR 25 mg/m(2) daily x 3 and ARA-C 1.5-2.0 gm/m(2) BSA every 12 hours for 12 doses. Consolidation doses of DNR were the same but ARA-C 100 mg/m(2) BSA/day x 5 was given by continuous intravenous infusion. The complete remission rate for patients less than 60 years was 69.9% (95% CI: 59.5-79.0%) and 47.2% (95% CI: 33.3-61.4%) for the older patients. The median duration of first remission for the younger patients was 13.0 months and of overall survival 17.9 months; for patients over 60 years 5.6 and 10.0 months respectively. Disease-free survival and overall survival of the 19 patients receiving alloBMT and the 13 patients undergoing autoBMT aged less than 55 years and in first or second complete remission were significantly increased compared with 22 patients in remission but not having BMT (p < 0.001 and p < 0.013). The results support the effectiveness of high-dose ARA-C for remission induction, a need for intensive consolidation therapy and a role for BMT in the management of AML.

Purpose: To optimize followup in patients with stage I nonseminomatous testis cancer on surveillance we evaluated the contribution of each followup modality to the detection of progression as well as morbidity and mortality outcomes., Materials and Methods: After orchiectomy 170 patients with clinical stage I nonseminoma were prospectively placed on a surveillance protocol. History, physical examination, serum tumor markers, abdominal and pelvic computerized tomography (CT), and chest x-ray were used for followup. The number of failures, methods and timing of progression detection, treatments required, mortality rate and subsequent contralateral primary tumors were recorded., Results: The 170 surveillance patients were followed a median of 6.3 years. Within 2 years (median 6.9 months) postoperatively 48 patients (28.2%) had disease progression. History, physical examination, markers, CT and chest radiography provided the initial evidence of progression in 18 (37.5%), 34 (70.8%), 34 (70.8%), and 4 (8.3%) patients, respectively. Each modality was the only indicator of failure in 2 (4.2%), 4 (8.3%), 10 (20.8%) and 0 cases, respectively. Of the 170 patients 122 (71.8%) required no additional treatment beyond orchiectomy, 26 (15.3%) received 1 and 22 (12.9%) underwent more than 1 therapeutic modality. Only 1 patient (0.6%) died of disease. Contralateral tumors developed in 5 cases (2.9%) therapeutic a mean of 8.1 years after orchiectomy., Conclusions: In stage I nonseminoma patients, surveillance history, physical examination, tumor markers and abdominopelvic CT are necessary components of the followup protocol. Removal of routine chest x-ray from the protocol would not have changed progression detection. The initial surveillance visit must occur by 2 months postoperatively. Patients should be followed beyond 5 years and likely for life in addition to regular patient self-examination.

Testicular seminoma is an uncommon tumor that accounts for approximately 50% of all germ cell testicular tumors. The vast majority of patients present with early-stage disease and almost all patients are cured of their disease. Management is based on disease extent with patients with stage I seminoma having numerous treatment options, varying from surveillance to adjuvant retroperitoneal radiation therapy and prophylactic adjuvant single-agent chemotherapy. Only 20% of patients present with more advanced disease; the majority of those have stage II disease with retroperitoneal lymph node involvement. The standard management is retroperitoneal radiation therapy with chemotherapy being used for patients with bulky disease. Systemic chemotherapy with cisplatin alone or etoposide and cisplatin is the standard approach to advanced and metastatic disease with cure rates approaching 85% to 90%. The goal of treatment is a cure with a minimum of complications. The current controversies include the optimum management of residual retroperitoneal mass (post-radiation therapy or chemotherapy), the management of patients with second testicular or bilateral testicular tumors, the management of testicular intraepithelial neoplasia, and the management of seminoma in immunosuppressed patients.

Purpose: We sought to identify prognostic factors predictive of disease progression in patients with clinical stage I seminoma on surveillance following orchiectomy., Materials and Methods: Between January 1981 and December 1993, 201 patients 20 to 86 years old (median age 34) with clinical stage I seminoma were placed on surveillance following orchiectomy. The potential prognostic factors studied included age, tumor size, mitotic count, S phase fraction, ploidy, presence of small vessel invasion, syncytiotrophoblasts and tumor infiltrating lymphocytes, expression of beta-human chorionic gonadotropin and low molecular weight keratin on immunohistochemistry., Results: With a median followup of 6.1 years (range 1.3 to 12.3) 31 patients had relapse for an actuarial 5-year relapse-free rate of 84.9%. The 5-year actuarial survival rate was 97.1% and the cause specific survival rate was 99.5%. On univariate analysis factors predictive of relapse were tumor size (5-year relapse-free rate 88 and 67% for tumors 6 cm. or less and greater than 6 cm., respectively, p = 0.004), age (5-year relapse-free rate 79 and 91% for age 34 years or younger versus older than 34 years, respectively, p = 0.009) and presence of small vessel invasion (5-year relapse-free rate 86 versus 69%, p = 0.01). On multivariate analysis age and tumor size were predictive of relapse, while small vessel invasion approached statistical significance. The risk of relapse in 57 patients with none of the 3 adverse prognostic factors (age greater than 34 years, tumor 6 cm. or smaller and no small vessel invasion) was 6%., Conclusions: We identified age, size of the primary tumor and small vessel invasion as important prognostic factors for relapse in patients with stage I seminoma treated with surveillance. Further followup and assessment of biological factors are needed to optimize selection of patients at a high risk for relapse who should receive immediate postoperative therapy.

Purpose: To assess the results of treatment and patterns of relapse in a contemporary group of patients with stage I testicular seminoma managed by adjuvant radiation therapy (RT) and surveillance., Patients and Methods: Between January 1981 and December 1991, 364 patients with stage I seminoma were treated at Princess Margaret Hospital. Of these, 194 were treated with adjuvant RT (92% received a dose of 25 Gy in 20 fractions for 4 weeks) and 172 were managed by surveillance. Two patients were included in this series twice--both had postorchiectomy RT for stage I disease, developed a contralateral seminoma, and were placed on surveillance and analyzed for outcome of both primary tumors. The median follow-up period for patients treated with adjuvant RT was 8.1 years (range, 0.2 to 12), and for patients managed by surveillance, it was 4.2 years (range, 0.6 to 10.1)., Results: The overall 5-year actuarial survival rate for all patients was 97%, and the cause-specific survival rate was 99.7%. Only one patient died of seminoma. Of 194 patients treated with RT, 11 have relapsed, with a 5-year relapse-free rate of 94.5%. Prognostic factors for relapse included histology, tunica invasion, spermatic cord involvement, and epididymal involvement. Twenty-seven patients developed disease progression on surveillance, which resulted in a 5-year progression-free rate of 81.9%. The only factor identified to predict progression on surveillance was age at diagnosis: patients aged < or = 34 years had a 26% risk of progression at 5 years, in contrast to a 10% risk of progression in those greater than 34 years of age., Conclusion: The outcome of patients with stage I testicular seminoma is excellent, with only one of 364 patients (0.27%) dying of disease. In our experience, both a policy of adjuvant RT and of surveillance resulted in a high probability of cure. Our surveillance experience showed that four of five patients with stage I seminoma are cured with orchiectomy alone. The benefit of adjuvant RT was reflected in a decreased relapse rate. We have identified a number of prognostic factors for relapse in patients managed with both approaches, but further study of prognostic factors is required, particularly to identify patients at high risk of disease progression on surveillance.

The authors present a case of surgical transposition of the left ovary, which presented on computed tomography (CT) as an intraperitoneal cystic mass. To their knowledge, there is only one other report in the radiologic literature of the CT appearance of a transposed ovary, but in that case the ovary appeared as a retroperitoneal mass.

Purpose: Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the Princess Margaret Hospital experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma., Methods and Materials: Fifty-two patients treated at the PMH between 1978 and 1986 were identified and their records reviewed retrospectively. Staging procedures revealed 16 patients with Stage I, 28 with Stage II, and eight with Stages III or IV disease. Five patients were treated on a protocol designed for anaplastic carcinoma of thyroid and they were excluded from detailed analysis. Of 39 patients with Stages I and II disease, 18 were treated with radiotherapy alone, three chemotherapy alone, and 18 combined modality therapy. Combined modality therapy was used mainly in patients with large tumor bulk., Results: The overall 5-year actuarial survival and cause-specific survival were 56% and 64%, respectively. The overall relapse-free rate was 61% at 5 years. Among the 39 patients with Stages I and II disease, the 5-year actuarial survival, cause-specific survival, and relapse-free rate were 64%, 73%, and 66%, respectively. There were no significant differences in outcome between those treated with radiotherapy alone and those treated with combined modality therapy (cause-specific survival: p = 0.25, relapse: p = 0.06). A univariate analysis showed that the only variable to reach statistical significance was tumor bulk. Age was marginally significant while stage and histology were not statistically significant, possibly due to the fairly homogeneous distribution of patients in each of these variables. Patients with progression or relapse of lymphoma after initial treatment frequently died of disease. Isolated gastrointestinal relapses occurred in three cases, representing 27% of all relapses., Conclusion: Based on the above results, we recognize that the majority of patients with localized thyroid lymphoma require combined modality therapy and we recommend radiotherapy alone only for a small, select group of patients with Stage I disease and small tumor bulk.

Purpose: To determine what proportion of patients with Stage I testicular seminoma will be cured with orchidectomy alone., Methods and Materials: From August 1984 to December 1991 148 patients with Stage I testicular seminoma were entered on a prospective study of surveillance following orchidectomy. The eligibility criteria included a normal chest X ray, lymphogram, computed tomography (CT) of the abdomen and pelvis, and normal post-orchidectomy tumor markers (AFP and BHCG). Patients were followed with a clinical assessment (markers, chest X ray and CT abdomen and pelvis) at 4 to 6 monthly intervals., Results: With a median follow-up of 47 months (range 7-87 months), the actuarial relapse-free rate was 81% at 5 years. Twenty-three patients have relapsed with a median time to relapse of 15 months (range 2-61 months). Four patients (17%) relapsed at 4 or more years from diagnosis. Twenty-one of the 23 relapses occurred in the paraaortic lymph nodes, one patient relapsed in the mediastinum and ipsilateral inguinal nodes and one patient had an isolated ipsilateral inguinal node relapse. Nineteen patients were treated for relapse with external beam radiation therapy of which three developed a second relapse and were salvaged with chemotherapy. Four patients were treated for first relapse with chemotherapy and one developed a second relapse and died of disease. Age at diagnosis was the only prognostic factor for relapse, with patients age < or = 34 having an actuarial relapse-free rate at 5 years of 70% in contrast to a 91% relapse-free rate in those > 34 years of age., Conclusions: We recommend that surveillance in Stage I testicular seminoma should only be performed in a study setting until further data regarding the risk of late relapse and the efficacy of salvage chemotherapy is available.

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.

Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.

Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radiation therapy. Acute complications included nausea and vomiting in 364 patients (61%) which were severe in 36, and diarrhea in 407 patients (68%), severe in 35. Leukopenia (less than 2.0 x 10(9) cells/liter) and thrombocytopenia (less than 100 x 10(9) cells/liter) occurred in 64 patients (11%) each. Treatment interruptions occurred in 136 patients (23%), and 62 patients (10%) did not complete treatment. In both situations the most common cause was myelosuppression. Late complications included chronic diarrhea in 85 patients (14%), transient hepatic enzyme elevation in 224 (44%), and symptomatic basal pneumonitis in 23 (4%). Serious late bowel complications were infrequent: 25 patients (4.2%) developed bowel obstruction and 16 required operation. Multivariate analysis was unable to determine any significant prognostic factors for bowel obstruction; however, the moving-strip technique of radiation therapy was associated with a significantly greater risk of developing chronic diarrhea, pneumonitis, and hepatic enzyme elevation than was the open beam technique. We conclude that abdomino-pelvic radiation therapy as used in these patients is associated with modest acute complications and a low risk of serious late toxicity.

We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.

Heterogeneity in psychosexual responses to disease-specific diagnosis is demonstrated for two groups of cancer patients with testis cancer and Hodgkin's disease who are comparable in prognosis and treatment intensity. The two groups of patients and their partners are shown to differ in their ability to recover from psychiatric problems associated with the diagnosis and/or treatment of cancer.

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years (P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% (P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.

Heterogeneity in psychiatric responses to disease specific diagnosis is demonstrated for two groups of cancer patients who are comparable in prognosis and treatment intensity. Implications of this heterogeneity are drawn for etiological study and for planning psychiatric interventions.

We describe a case of erythema nodosum associated with non-Hodgkin's lymphoma. The course and resolution of the erythema nodosum correlated most closely with a breakdown and release of new antigen at the start of a new regimen of chemotherapy.

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.

The authors have investigated the diagnostic accuracy of computed tomography (CT) of the abdomen and pelvis in the assessment of patients prior to second-look laparotomy for advanced ovarian cancer. CT studies (read independently by three radiologists) and laparotomy findings were analyzed in 50 patients. Sensitivity varied from 0.30 to 0.65 among the radiologists, specificity from 0.44 to 0.89, positive predictive value from 0.50 to 0.73, and negative predictive value from 0.60 to 0.70. Receiver operator curve analysis of the data indicated poor performance of CT as a diagnostic test. The authors also examined some problems in interpreting their data and that of others in the literature, in particular, the influence of potential sources of bias.

Peripheral eosinophilia is a rare but recognized accompaniment of malignant disease. Two unusual cases, one with a histiocytic lymphoma and the other with cervical carcinoma, are described. In the first patient, pulmonary infiltrates developed at the height of the eosinophilia and in the second, the peripheral eosinophilia heralded the onset of disseminated disease. Tumor-associated peripheral eosinophilia is reviewed, and it is concluded that peripheral eosinophilia associated with a malignant setting is a marker of extensive disease and is thus associated with a poor prognosis.

An analysis of 231 patients with stages I, II, and asymptomatic III ovarian cancer, studied in a prospective randomized-stratified trial, is presented. None of the stage IA patients with well-differentiated tumors have had disease relapses; one fourth of the patients with poorly differentiated tumors have had disease relapses throughout the peritoneal cavity. There is therefore little justification for pelvic radiation alone as postoperative therapy for stage IA ovarian carcinoma. For stage IB, II, and asymptomatic III presentations, patients with an incomplete initial pelvic operation had poor survival characteristics with all tested therapies. For patients in whom the operation was completed, abdominopelvic radiation was superior to pelvic radiation alone or followed by chlorambucil, with respect to long-term survival and control of abdominal disease. The effectiveness of abdominopelvic radiation was independent of stage or histology. The value of abdominopelvic radiation was most strikingly seen in patients with no visible residual tumor.

The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (+/- SD) of 46.2 +/- 20.2 min during the first course and 37.8 +/- 18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (+/- SD) of 57.8 +/- 19.3 h during the first course and 86.6 +/- 33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61 +/- 0.32 l/h/m2 and 0.45 +/- 0.16 l/h/m2 for the first and the second course, respectively. We conclude that: urinary platinum excretion is variable between patients and with time; a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and the body's elimination pathways clear less platinum upon repeat administration.

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 disposition of cyclophosphamide was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, doxorubicin (adriamycin) 50 mg/m2 and cisplatin 50 mg/m2 during their first and second courses of therapy. Plasma samples were obtained over 24 h following the completion of the cyclophosphamide infusion and assayed for cyclophosphamide by high performance liquid chromatography. The mean disposition of cyclophosphamide conformed to a 2-compartment model with a mean terminal half-life of 7.14 h on the first course and 8.77 h on the second course. Mean area under the plasma concentration versus time curve appeared to increase from 248.8 mg.h/l for the initial course to 282.2 mg.h/l on the second. Mean total body clearance was 2.01 l/h/m2 on the first course and 1.77 l/h/m2 on the second. Volume of distribution on the first and second courses were 15.3 l/m2 and 18.1 l/m2, respectively. These results suggested that cyclophosphamide clearance decreased when given in a bolus fashion every 3 weeks. However, inter-patient and intra-patient variability was large and the differences in the calculated parameters were not statistically significant when the individual patient data was considered. It is concluded that: 1. cyclophosphamide disposition can best be fit by a bi-exponential equation; 2. considerable intra- and interpatient variability in the concentration-time profile will be encountered; 3. cyclophosphamide disposition does not change from the first to the second course. Reasons for the wide variation are proposed.

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of carboplatin (400 mg/m2) given as an iv bolus every 4 weeks in patients with measurable advanced ovarian cancer who had failed or relapsed following standard platinum-containing therapy. Four complete and eight partial responses were seen in 43 evaluable patients. Toxicity was primarily hematologic. Myelosuppression, particularly thrombocytopenia, was severe in one-third of patients treated at the 400-mg/m2 starting dose. Carboplatin has antitumor activity in this clinical setting, but a lower starting dose is recommended.

We have examined the reliability of computed tomography (CT) in the assessment of patients with advanced ovarian cancer. Three radiologists independently read the same set of 140 CT scans. Fifty percent of the films were reread by the same radiologist to assess intraobserver agreement. In addition we assessed variability among radiologists in reporting signs of disease such as a mass and ascites and the variability in reporting a change in signs in response to therapy. Intraobserver agreement on the identification of signs such as a mass and ascites and on overall response to therapy was moderate to excellent (Kappa 0.52-0.84). Agreement among observers on the same signs was not as good (Kappa 0.36-0.79).