Impact of Granulocyte-colony Stimulating Factor on Bleomycin-induced Pneumonitis in Chemotherapy-treated Germ Cell Tumors.

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.

Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in patients with disseminated germ cell tumors treated with chemotherapy.

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.

Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience.

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.

No role for routine chest radiography in stage I seminoma surveillance.

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.

Stage II testicular seminoma: patterns of recurrence and outcome of treatment.

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.

Appropriate radiation volume for stage IIA/B testicular 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: aggressive chemoradiation therapy is required after surgery.

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.

Accuracy of recorded tumor, node, and metastasis stage in a comprehensive cancer center.

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.