Remote Monitoring and Data Collection for Decentralized Clinical Trials.

Importance: Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies. Objective: To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials. Design, Setting, and Participants: The Bloomberg New Economy International Cancer Coalition, composed of patient advocacy, industry, government regulator, and academic medical center representatives, developed a survey directed to global biopharmaceutical companies of the coalition from October 1 through December 31, 2022, with a focus on registrational clinical trials. The data for this survey study were analyzed between January 1 and 31, 2023. Exposure: Adoption of decentralized clinical trial technologies. Main Outcomes and Measures: The survey measured (1) outcomes of different remote monitoring and data collection technologies on patient centricity, (2) adoption of these technologies in oncology and all therapeutic areas, and (3) barriers and facilitators to adoption using descriptive statistics. Results: All 8 invited coalition companies completed the survey, representing 33% of the oncology market by revenues in 2021. Across nearly all technologies, adoption in oncology trials lags that of all trials. In the current state, electronic diaries and electronic clinical outcome assessments are the most used technology, with a mean (SD) of 56% (19%) and 51% (29%) adoption for all trials and oncology trials, respectively, whereas visits within local physician networks is the least adopted at a mean (SD) of 12% (18%) and 7% (9%), respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 of the 11 technologies surveyed. Furthermore, digitally enabled recruitment, local imaging capabilities, and local physician networks were identified as technologies that could be most effective for improving patient centricity in the long term. Conclusions and Relevance: These findings may help to galvanize momentum toward greater adoption of enabling technologies to support a new paradigm of trials that are more accessible, less burdensome, and more inclusive.

The Association Between Statin Use and Outcomes in Patients Initiating Androgen Deprivation Therapy.

BACKGROUND: Studies have conflicting results regarding the association between statin use and biochemical recurrence for prostate cancer (PCa). A limited number of studies examining statins in advanced stages report positive results, with a few specifically examining statins and androgen deprivation therapy (ADT). OBJECTIVE: To perform a post hoc secondary analysis of a randomised controlled trial (RCT) of men initiating ADT to examine the association between statin use and outcomes. DESIGN, SETTING, AND PARTICIPANTS: Patients with prostate-specific antigen (PSA) >3 ng/ml >1 yr following primary/salvage radiotherapy were enrolled in an RCT of intermittent androgen deprivation (IAD) versus continuous ADT (NCT00003653). Baseline and on-study statin use was modelled as a time-dependent covariate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival. Models were adjusted for age, time from radiotherapy to ADT, baseline PSA, and prior ADT. RESULTS AND LIMITATIONS: Of 1364 patients, statin users (585; 43%) were younger (72.7 vs 73.8 yr, p = 0.001) and less likely to have PSA >15 ng/ml (20% vs 25%, p = 0.04). After a median follow-up of 6.9 yr, statin use was associated with reduced overall (hazard ratio [HR]: 0.64; 95% confidence interval [CI] 0.53-0.78, p < 0.001) and PCa-specific (HR: 0.65, 95% CI 0.48-0.87, p = 0.004) mortality. Statin users had 13% longer time to castration resistance, but this did not reach statistical significance (p = 0.15). As an exploratory endpoint, in the IAD arm, statin users had longer time off treatment (median: 0.85 vs 0.64 yr, p = 0.06). Limitations include potential for residual confounding between statin users and nonusers, and confounding by indication. CONCLUSIONS: In men treated with ADT following primary or salvage radiotherapy, statin use was associated with improved overall and PCa-specific survival. In patients treated with IAD, statin use was associated with a trend towards longer time off treatment. A prospective trial of statins in men commencing ADT is warranted. PATIENT SUMMARY: We found a favourable association between statin use and survival outcomes in patients initiating androgen deprivation therapy.

Global palliative radiotherapy: a framework to improve access in resource-constrained settings.

Radiotherapy is an essential component of cancer therapy. Lack of access to radiotherapy in less-developed countries prevents its use for both cure and symptom relief, resulting in a significant disparity in patient suffering. Several recent initiatives have highlighted the need for expanded access to both palliative medicine and radiotherapy globally. Yet, these efforts have remained largely independent, without attention to overlap and integration. This review provides an update on the progress toward global palliative radiotherapy access and proposes a strategic framework to address further scale-up. Synergies between radiotherapy, palliative medicine, and other global health initiatives will be essential in bringing palliative radiotherapy to patients around the globe.

PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer.

BACKGROUND: The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC). METHODS: From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test. RESULTS: Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004). CONCLUSIONS: For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society.

Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities, 3rd edition.

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.

Clinical characteristics and early treatment outcomes of follicular lymphoma in young adults.

Follicular lymphoma (FL) in young adults (YA, <40 years old) is uncommon, and the clinical characteristics and outcomes of this group are not well defined. We conducted a retrospective database review of 427 patients with newly diagnosed FL aged 65 years or less registered at Princess Margaret Cancer Centre between 1995 and 2010. YA (n = 61) and those 40-65 (n = 366) were compared with regards to clinical stage at diagnosis, FL International Prognostic Index (FLIPI) score, and the following clinical outcomes: time to second treatment, cause-specific survival (CSS) and overall survival (OS). At diagnosis, stage and FLIPI score were similar, as were the proportion of patients requiring therapy (YA 75% versus older adults 71%). Median follow-up was 8.1 years. Time to second therapy was similar in both age groups (5-year probability 23% YA versus 27% older adults; Gray's P-value = 0.76). Ten-year OS was significantly higher for YA (87% versus older adults 72%; P = 0.029). On multivariate analysis, age <40 years, low FLIPI score and observation as initial management were favourable prognostic factors for OS and CSS. We conclude that YA with FL have a favourable prognosis compared to older patients; whether this reflects competing mortality risks or age-related differences in lymphoma biology warrants further investigation.

Active breathing control for patients receiving mediastinal radiation therapy for lymphoma: Impact on normal tissue dose.

PURPOSE: Active breathing control (ABC) is emerging as a tool to reduce heart and lung dose for lymphoma patients receiving mediastinal radiation therapy (RT). The objective of this study was to report our early institutional experience with this technique, with emphasis on quantifying the changes in normal tissue dose and exploring factors that could be used to select patients with the greatest benefit. METHODS AND MATERIALS: Patients receiving mediastinal involved-field RT (IFRT) for lymphoma were eligible. The ABC was performed using a moderate deep-inspiration breath-hold (mDIBH) technique. All patients were replanned with free-breathing (FB) computed tomographic data sets and comparisons of lung, cardiac, and female breast tissue doses were made between mDIBH and FB plans. Logistic regression models were used to identify factors associated with improvement in mean lung and heart dose with mDIBH. RESULTS: Forty-seven patients were analyzed; the majority (87.2%) had Hodgkin lymphoma. Median prescribed dose was 30 Gy (range, 20-36 Gy), with 78.7% of cases being treated with parallel-opposed beams. The use of mDIBH significantly improved average mean lung dose (FB: 11.0 Gy; mDIBH: 9.5 Gy; P < .0001), lung V20 (28% vs 22%; P < .0001), and mean heart dose (14.3 Gy vs 11.8 Gy; P = .003), but increased the mean breast dose (FB: 3.0 Gy; mDIBH 3.6 Gy; P = .0005). The magnitude of diaphragmatic excursion on the inhale scan was significantly associated with dosimetric improvement in both heart and lung dose with mDIBH. CONCLUSIONS: Mediastinal IFRT for lymphoma delivered with mDIBH can significantly reduce lung and heart dose compared with FB, although not for all patients, and may increase breast dose in females. Its implementation is achievable in both adult and pediatric populations. Further work is necessary to better predict which patients benefit from this technique.

Role of radiotherapy in patients with early-stage diffuse large B-cell lymphoma of Waldeyer's ring in remission after anthracycline-containing chemotherapy.

Consolidation radiotherapy (cRT) in patients with stage I/II diffuse large B-cell lymphoma of the Waldeyer's ring (WR-DLBCL) in complete remission (CR) after induction chemotherapy (CHT) is often associated with relevant acute and chronic toxicity, and its impact on survival remains to be defined. A total of 184 patients in CR after anthracycline-based chemotherapy were retrospectively analyzed: 62 underwent CHT alone (CHT group), while 122 (66%) patients were referred to cRT (CHT + RT group). After a median follow-up of 54 months, 36 patients (20%) experienced relapse: 19% in the CHT group and 20% in the CHT + RT group. At the time of analysis 47 (76%) CHT patients and 97 (80%) CHT + RT patients were alive. Five-year overall survival (OS), disease-free survival (DFS) and lymphoma-specific survival (LSS) were 80%, 74% and 86%, respectively. Five-year OS was significantly prolonged in the CHT + RT group, while DFS and LSS were similar between groups. This discrepancy was attributed to a high percentage of deaths due to unrelated causes in CHT patients. cRT does not prolong LSS in patients with early-stage WR-DLBCL in CR after anthracycline-containing chemotherapy. An international confirmatory trial is warranted.

Limited-stage mantle cell lymphoma: treatment outcomes at the Princess Margaret Hospital.

Mantle-cell lymphoma (MCL) is a rare cancer, with the majority of patients (pts) presenting in stage III-IV and the outcomes are poor. To determine the curability of localized MCL, we examine stage I-II pts at our institution between 1990-2007. 26 pts with stage I (38%) and stage II (62%) were referred. Sites involved were head and neck in 73%. Five had a blastoid variant. Five patients were treated with palliative intent. Analysis was focused on pts treated with a curative intent (21 pts): 17 CT+RT, 2 RT, 2 CT followed by ASCT. 13 patients received CHOP, 5-RCHOP, 1-CVP; most received 6 cycles. The RT median dose was 35Gy and IFRT for the majority. For 21 pts treated with a curative intent, median follow up was 5.8 years. The overall response rate was 95%. Among the 19 CR/CRu pts, 9 relapsed for a 5-year relapse rate of 46%. Relapses were mainly observed at distant sites, 3 were in GI tract, 1 had both local and distant relapse. Median PFS and OS were 3.2 and 6.4 years, respectively. 5-year OS was 62%. In univariate analysis, blastoid variant and stage II were prognostic factors for PFS. Multivariate analysis could not be performed due to the small sample size. With a treatment approach using combined CT+RT for stage I-II MCL, local control was achieved in 94%. Systemic relapse remains a significant problem, especially for stage II and blastoid variant. Radiotherapy should remain part of curative treatment plan in stage I-II MCL.

Intermittent androgen suppression for rising PSA level after radiotherapy.

BACKGROUND: Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS: We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS: Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24). CONCLUSIONS: Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.).

Role of salvage radiation therapy for patients with relapsed or refractory hodgkin lymphoma who failed autologous stem cell transplant.

PURPOSE: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). PATIENTS AND METHODS: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). RESULTS: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). CONCLUSION: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.

ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma.

BACKGROUND: Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths. METHODS: We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival. RESULTS: The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or early toxic effects from the treatment and 20 were related to another cause. CONCLUSIONS: Among patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).

Localized orbital mucosa-associated lymphoma tissue lymphoma managed with primary radiation therapy: efficacy and toxicity.

PURPOSE: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). METHODS AND MATERIALS: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. RESULTS: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). CONCLUSIONS: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial.

PURPOSE: Primary testicular lymphoma (PTL) has poor prognosis with failures in contralateral testis, CNS, and extranodal sites. To prevent these events, we designed an international phase II trial (International Extranodal Lymphoma Study Group 10 [IELSG-10]) that addressed feasibility and activity of conventional chemoimmunotherapy associated with CNS prophylaxis and contralateral testis irradiation. The trial was conducted by the IELSG and the Italian Lymphoma Foundation. PATIENTS AND METHODS: Fifty-three patients (age 22 to 79 years) with untreated stage I or II PTL were treated with six to eight courses of rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days (R-CHOP21); four doses of intrathecal methotrexate (IT-MTX) and radiotherapy (RT) to the contralateral testis (30 Gy) for all patients and to regional lymph nodes (30 to 36 Gy) for stage II disease. RESULTS: All patients received R-CHOP21, 50 received CNS prophylaxis, and 47 received testicular RT. With a median follow-up of 65 months, 5-year progression-free survival and overall survival rates were 74% (95% CI, 59% to 84%) and 85% (95% CI, 71% to 92%), respectively. Ten patients relapsed or progressed: two in lymph nodes, five in extranodal organs, and three in the CNS. The 5-year cumulative incidence of CNS relapse was 6% (95% CI, 0% to 12%). No contralateral testis relapses occurred. Ten patients died: lymphoma (n = 6), secondary leukemia (n = 2), heart failure (n = 1), and gastric cancer (n = 1). Grade 3 to 4 toxicities were neutropenia, 28%; infections, 4%; and neurologic, 13%. No deaths occurred as a result of toxicity. CONCLUSION: This international prospective trial shows that combined treatment with R-CHOP21, IT-MTX, and testicular RT was associated with a good outcome in patients with PTL. RT avoided contralateral testis relapses, but CNS prophylaxis deserves further investigation.

High response rate and improvement of long-term survival with combined treatment modalities in patients with poor-risk primary thyroid diffuse large B-cell lymphoma: an International Extranodal Lymphoma Study Group and Intergruppo Italiano Linfomi study.

The impact of different treatment modalities and prognostic factors on the clinical course of primary thyroid diffuse large B-cell lymphoma (PTDLBCL) is still the subject of research. This study was conducted to clarify these clinical aspects of this disorder. The clinical parameters of 48 patients with PTDLBCL at time of diagnosis were comparable to those of previous studies. Patients underwent either radiotherapy (RT)  ±  surgery (SX), chemotherapy (CHT) alone or in combination with local treatments (RT or SX), or SX followed by CHT and RT. A 90% complete remission (CR) rate was observed among patients who underwent combined treatment modalities (CTM), compared to 76% among the others. The 5-year progression-free survival differed significantly between both groups (p = 0.028). Poor performance status and advanced age correlated with decreased survival. PTDLBCL is a curable disease prevalent in elderly patients. Combined treatment modalities were able to induce an elevated rate of CR, improving long-term survival in younger patients. However, the outcome in elderly patients still remains unsatisfactory.

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.