Long-term Surveillance of Patients with Complete Response Following Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumor.

BACKGROUND: There is controversy regarding the management of patients with normal markers and residual masses (≤1 cm) after chemotherapy for nonseminomatous germ cell tumors (NSGCTs). OBJECTIVE: To determine long-term outcomes of a surveillance strategy in such patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of our multidisciplinary testicular cancer database was performed. All patients who underwent primary chemotherapy for metastatic NSGCTs were identified between 1981 and 2016. A complete response (CR) was defined as normalization of serum tumor markers and a ≤1 cm residual mass in the largest axial dimension following chemotherapy. All such patients were surveilled. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome variables of interest were time to death, time to cancer-specific survival, and time to relapse. Overall survival and relapse-free survival were calculated using the Kaplan-Meier method, and the cumulative incidence of cause-specific survival rates was calculated using competing risk analysis. The impact of risk group and chemotherapy regimen on relapse-free survival was assessed using log-rank test. RESULTS AND LIMITATIONS: During the study period, 1429 metastatic germ cell tumor patients were treated with primary chemotherapy. CR was achieved in 191 (18.5%) NSGCT patients. The median age at diagnosis was 27.4 yr, with a median follow-up of 81.1 mo. The majority had American Joint Committee on Cancer stage II at diagnosis (I: 23.8%; II: 49.2%; III: 27%) and International Germ Cell Cancer Collaborative Group good-risk disease (good: 78%; intermediate: 17.8%; poor: 4.2%). Of the 191 patients with a CR, 175 (91.6%) never relapsed and remain disease free. Sixteen (8.4%) patients relapsed after a median of 11.3 mo (range 1-332 mo), with over half (nine patients; 4.7%) relapsing in the retroperitoneum only and salvaged successfully with postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) alone. Of these nine patients, only two (1%) had viable disease in the PC-RPLND specimen. The remaining seven patients had relapses outside the retroperitoneum and received salvage chemotherapy ± postchemotherapy resection. Overall, nine (4.7%) patients have died, but only four (2.1%) from testis cancer. CONCLUSIONS: Our data, the largest series to date, confirm that surveillance is safe and effective for men who achieve a CR following chemotherapy for metastatic NSGCTs. PATIENT SUMMARY: Surveillance is a safe strategy for patients who achieve a complete response following chemotherapy for metastatic testis cancer.

Detection of Relapse by Low-dose Computed Tomography During Surveillance in Stage I Testicular Germ Cell Tumours.

BACKGROUND: Standard-dose computed tomography (SDCT) scans are associated with radiation exposure during stage I testicular cancer surveillance. OBJECTIVE: To evaluate low-dose CT (LDCT) for clinical use. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm prospective study, patients on surveillance for stage I testicular germ cell tumour underwent SDCT and LDCT scans on their first visit after enrolment. The adequacy of LDCT image quality was assessed for subsequent use. Patients were followed with LDCT only and suspected relapse was confirmed by SDCT. OUTCOME MEASURES AND STATISTICAL ANALYSIS: We assessed whether initial LDCT scans were of sufficient quality for routine clinical use. We compared mean differences in nodal size at relapse between LDCT and SDCT using a one-sample paired t test. The relapse free-rate was calculated using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Of 257 patients, one was excluded because of inadequate image quality. At median follow-up of 5.25 yr, 35 patients had relapsed, 33 with retroperitoneal lymphadenopathy. The 2- and 5-yr relapse-free rates were 89.5% and 85.3%, respectively. The mean size of retroperitoneal nodal relapse was 17.3 and 17.5mm on the short axis, 23.2 and 22.7mm on the long axis, and 26.1 and 26.7mm on craniocaudal length for LDCT and SDCT, respectively. The mean difference between LDCT and SDCT was 0.14mm (p=0.55) short axis, -0.54mm (p=0.092) long axis, and -0.51mm (p=0.086) length. A limitation was the lack of a control arm. CONCLUSIONS: LDCT image quality was adequate for clinical use, and retroperitoneal nodal relapse was detected with minimal differences seen between LD and SDCT. LDCT can be safely adopted and will decrease overall radiation exposure in stage I germ cell tumour surveillance. PATIENT SUMMARY: We studied the use of low-dose computed tomography scans for detecting testicular cancer recurrence in lymph nodes of the abdomen and pelvis and found that they were safe, effective and would potentially reduce overall X-ray exposure. This trial is registered at ClinicalTrials.gov as NCT03142802.

Treatment of Relapse of Clinical Stage I Nonseminomatous Germ Cell Tumors on Surveillance.

PURPOSE: Active surveillance (AS) for testicular nonseminomatous germ cell tumors (NSGCT) is widely used. Although there is no consensus for optimal treatment at relapse on surveillance, globally patients typically receive chemotherapy. We describe treatment of relapses in our non-risk-adapted NSGCT AS cohort and highlight selective use of primary retroperitoneal lymph node dissection (RPLND). METHODS: From December 1980 to December 2015, 580 patients with clinical stage I NSGCT were treated with AS, and 162 subsequently relapsed. First-line treatment was based on relapse site and extent. Logistic regression was used to explore factors associated with need for multimodal therapy on AS relapse. RESULTS: Median time to relapse was 7.4 months. The majority of relapses were confined to the retroperitoneum (66%). After relapse, first-line treatment was chemotherapy for 95 (58.6%) and RPLND for 62 (38.3%), and five patients (3.1%) underwent other therapy. In 103 (65.6%), only one modality of treatment was required: chemotherapy only in 58 of 95 (61%) and RPLND only in 45 of 62 (73%). Factors associated with multimodal relapse therapy were larger node size (odds ratio, 2.68; P = .045) in patients undergoing chemotherapy and elevated tumor markers (odds ratio, 6.05; P = .008) in patients undergoing RPLND. When RPLND was performed with normal markers, 82% required no further treatment. Second relapse occurred in 30 of 162 patients (18.5%). With median follow-up of 7.6 years, there were five deaths (3.1% of AS relapses, but 0.8% of whole AS cohort) from NSGCT or treatment complications. CONCLUSION: The retroperitoneum is the most common site of relapse in clinical stage I NSGCT on AS. Most are cured by single-modality treatment. RPLND should be considered for relapsed patients, especially those with disease limited to the retroperitoneum and normal markers, as an option to avoid chemotherapy.

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.

Phase I Clinical Trial of Everolimus Combined with Trimodality Therapy in Patients with Muscle-Invasive Bladder Cancer.

Background: Local control following trimodality therapy (TMT) for muscle-invasive bladder cancer (MIBC) requires further optimization. Objective: Evaluating the biologic endpoint, feasibility, and toxicity of integrating everolimus to TMT in patients with MIBC. Methods: This was a phase I trial in patients with MIBC who were not surgical candidates or who refused cystectomy. Following maximal transurethral tumor resection, patients were treated by radiotherapy (50 Gy/20 fractions), gemcitabine (100 mg/m2/weekly) and escalating doses of everolimus (2.5-5.0 mg/day). Everolimus was given daily for one month prior to radiation, during treatment, and one month post-radiation. Toxicity assessment followed the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Biologic endpoint with downregulation of phospho-S6 (pS6) was assessed using immunohistochemistry. Local response was evaluated with imaging and bladder biopsy post-therapy. Results: 10 patients were recruited; 8 males, 2 females. Median age was 78 years (range: 63-85). Four patients entered everolimus 2.5 mg cohort. Six other patients entered everolimus 5.0 mg cohort. Toxicities were encountered in 2 patients (Grade I), 6 patients (Grade II), 9 patients (Grade III) and 1 patient (Grade IV), with some experiencing more than one toxicity. Most Grade III and IV toxicities were encountered from everolimus alone prior to combination testing. Trial was terminated early due to toxicity. Interestingly, 6/10 patients (60%) achieved a complete response with negative post-treatment biopsies. Significant decrease of pS6 was demonstrated post-therapy (p = 0.03). Conclusions: Although combining everolimus with TMT achieved a biological endpoint and complete response in a significant number of patients with MIBC and negative prognostic factors, it was associated with unacceptable increased toxicity.

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.

Hypofractionated intensity modulated radiation therapy in combined modality treatment for bladder preservation in elderly patients with invasive bladder cancer.

PURPOSE/OBJECTIVE(S): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. METHODS AND MATERIALS: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. RESULTS: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. CONCLUSIONS: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid cystectomy.

Treatment burden in stage I seminoma: a comparison of surveillance and adjuvant radiation therapy.

OBJECTIVE: To examine the management and outcomes of patients with stage I seminoma and to relate these to overall treatment burden. PATIENTS AND METHODS: A total of 764 patients with stage I seminoma underwent surveillance or adjuvant radiation therapy (RT) at a single institution. First relapse on surveillance was managed with RT alone, or with combination chemotherapy (ChT) for more extensive recurrence. Second relapse was managed with ChT. Relapse after adjuvant RT was treated with ChT. The treatment burden was measured, according to the specific treatment undertaken after orchiectomy, by defining treatment episodes as follows: surgery - one episode; one course of RT - one episode; one course of ChT - one episode. RESULTS: In all, 484 patients underwent surveillance and 280 received adjuvant RT. The 5- and 10-year overall survival rates were 98.6 and 97.7% for surveillance, and 97.2 and 91.4% for adjuvant RT. A total of 72 (15%) patients in the surveillance group relapsed; treatment for relapse was RT (n = 56), ChT (n = 15) and surgery (n = 1). Second relapse occurred in six patients; these patients were treated with ChT. Of the patients in the adjuvant RT group, 14 (5%) relapsed: salvage treatment was 10 - ChT (n = 10) surgery (n = 1) and further RT (n = 3). The overall treatment burden represented by number of treatment episodes per patient was 0.16 in the surveillance group and 1.05 in the adjuvant RT group. CONCLUSIONS: Surveillance reduces the overall treatment burden in patients with stage I seminoma and is the preferred management option. The selective use of RT at first relapse for patients on surveillance leads to a similar requirement for subsequent ChT to that for patients on adjuvant RT.

Utility of serum tumor markers during surveillance for stage I seminoma.

BACKGROUND: The serum tumor markers α-fetoprotein (AFP), ß-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients with stage I seminoma. In this study, the authors evaluated the utility of routine measurement of these markers in the detection of disease relapse. METHODS: Data were gathered from a prospectively maintained database of patients who underwent surveillance for stage I testicular seminoma diagnosed between 1982 and 2005 at Princess Margaret Hospital. Patients were followed on a predefined schedule with physical examination (PE), serum tumor markers, abdominopelvic computed tomography, and chest x-rays. The records of patients who relapsed were examined for details of imaging and serum tumor markers throughout the period of follow-up until the time of relapse. RESULTS: Of the 527 patients who were managed by surveillance, 75 patients (14%) relapsed at a median follow-up of 72 months. Of these, 65 patients relapsed within the first 3 years and had routine serum tumor markers measured. In total, 11 patients had abnormal tumor markers at the time of relapse (AFP, 0 patients; HCG, 6 patients; LDH, 4 patients; and HCG and LDH, 1 patient). Only 1 patient had an elevated tumor marker (LDH) before relapse, as defined by an abnormal imaging study (n = 64) or physical examination (n = 1), for which the treatment and outcome were not affected. CONCLUSIONS: Serum tumor marker levels did not aid in the early diagnosis of disease relapse in patients with stage I seminoma who were managed with surveillance. The current results indicated that routine measurement of serum tumor markers can be discontinued safely in seminoma surveillance schedules.

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.

The Meaning-Making intervention (MMi) appears to increase meaning in life in advanced ovarian cancer: a randomized controlled pilot study.

OBJECTIVE: This pilot study aimed to provide supportive evidence for the acceptability and usefulness of the Meaning-Making intervention (MMi) in patients newly diagnosed with Stage III or IV ovarian cancer, and to provide estimates of parameters needed to design a full-scale study. METHODS: A randomized controlled trial with 24 patients (12 experimental and 12 control) was conducted. Existential well-being (primary outcome), overall quality of life, distress, anxiety, depression and self-efficacy were measured. RESULTS: Compared to the control group, patients in the experimental group had a better sense of meaning in life at one and three months post-intervention. CONCLUSION: The MMi seems a promising intervention for advanced cancer patients, and a full randomized controlled trial is warranted to further investigate its efficacy.

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.

Phase I trial of gemcitabine, doxorubicin and cisplatin (GAP) in patients with advanced solid tumors.

A phase I study was conducted to determine the recommended phase II dose, safety profile and anti-tumor activity of a combination regimen of gemcitabine, doxorubicin and cisplatin (GAP). Gemcitabine (G) and doxorubicin (A) were administered on days 1 and 8 at increasing doses (starting level 800 and 15 mg/m, respectively). Cisplatin (P) was given at a fixed dose of 50 mg/m2 (day 1). Treatment cycles were repeated every 3 weeks. Nineteen patients received 76 cycles of treatment. A and G were escalated up to 20 and 1000 mg/m2, and finally de-escalated to 15 and 800 mg/m2. The dose-limiting toxicity was neutropenic fever that was observed in 21% of the patients. Non-hematological toxicities included mild/moderate nausea, vomiting, diarrhea and fatigue, observed in 58, 37, 21 and 95% of the patients, respectively. Of 19 patients with evaluable disease, six patients had a partial response yielding an overall response rate of 31.6 % (95% confidence interval 12.6-56.6%) by intention-to-treat. We conclude that GAP is an active and tolerable treatment combination, with minimal visceral organ toxicities.

Consolidative abdominopelvic radiotherapy after surgery and carboplatin/paclitaxel chemotherapy for epithelial ovarian cancer.

PURPOSE: To assess the feasibility and morbidity of sequential cytoreductive surgery, carboplatin/paclitaxel chemotherapy, and consolidative abdominopelvic radiotherapy (APRT) in ovarian cancer. METHODS AND MATERIALS: Between 1998 and 2000, 29 patients with optimally cytoreduced epithelial ovarian cancer were treated with carboplatin (135 mg/m2) and paclitaxel (area under the curve [AUC] of 6) followed by APRT in a prospective protocol. All patients were clinically, radiographically, and biochemically (CA-125) free of disease at the completion of chemotherapy. Abdominopelvic radiotherapy was delivered using 6 MV anterior-posterior photon fields to encompass the peritoneal cavity. Median follow-up was 4 years. RESULTS: Two patients experienced Radiation Therapy Oncology Group Grade 3 gastrointestinal toxicity during APRT; 6 patients, Grade 3 or 4 neutropenia; and 3 patients, Grade 3 or 4 thrombocytopenia. Overall, 10 patients had Grade 3 or 4 acute toxicity. All of the acute side effects resolved after treatment was completed, and there were no serious consequences such as sepsis or hemorrhage. Abdominopelvic radiotherapy was abandoned prematurely in 3 patients. Late side effects were seen in 5 patients, including 1 small bowel obstruction, 2 symptomatic sacral insufficiency fractures, 1 case of severe dyspareunia, and 1 case of prolonged fatigue. All resolved with supportive management. The 4-year actuarial disease-free survival was 57%, and the overall survival was 92%. Eleven of 12 patients who relapsed received salvage chemotherapy, which was well tolerated. CONCLUSIONS: Abdominopelvic radiotherapy after optimal surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late side effects and does not limit subsequent salvage chemotherapy. Consolidative APRT warrants further investigation as a means of improving the outcome of patients with ovarian cancer.

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.