Peter Chung

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer

BACKGROUNDnPatients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer.nnnOBJECTIVEnTo determine cRR in CSI testicular cancer.nnnDESIGN, SETTING, AND PARTICIPANTSnWe reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time.nnnRESULTS AND LIMITATIONSnAt orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size <3cm, respectively. However, for patients without relapse within the first 2 yr of follow-up, the corresponding risk of relapse within the next 5 yr in the groups was 0.0%, 1.0% (95% confidence interval [CI] 0.3-1.7%), 5.6% (95% CI 3.1-8.2%), and 3.9% (95% CI 1.4-6.4%). Over time, cRR decreased (p≤0.021) in all models. Limitations include changes to surveillance protocols over time and few late relapses.nnnCONCLUSIONSnAfter 2 yr, the risk of relapse on surveillance for CSI testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients.nnnPATIENT SUMMARYnOur study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time.

Readout-segmented echo-planar diffusion-weighted imaging improves geometric performance for image-guided radiation therapy of pelvic tumors

BACKGROUND AND PURPOSEnDiffusion-weighted imaging using echo-planar imaging (EPI) is prone to geometric inaccuracy, which may limit application to image-guided radiation therapy planning, as well as for voxel-based quantitative multi-parametric or multi-modal approaches. This research investigates pelvic applications at 3 T of a standard single-shot (ssEPI) and a prototype readout-segmented (rsEPI) technique.nnnMATERIALS AND METHODSnApparent diffusion coefficient (ADC) accuracy and geometric performance of rsEPI and ssEPI were compared using phantoms, and in vivo, involving 8 patients prior to MR-guided brachytherapy for locally advanced cervical cancer, and 19 patients with prostate cancer planned for tumor-targeted radiotherapy. Global and local deviations in geometric performance were tested using Dice Similarity Coefficients (DC) and Hausdorff Distances (HD).nnnRESULTSnIn cervix patients, DC increased from 0.76±0.14 to 0.91±0.05 for the high risk clinical target volume, and 0.62±0.26 to 0.85±0.08 for the gross tumor target volume. Tumors in the peripheral zone of the prostate gland were partly projected erroneously outside of the posterior anatomic boundary of the gland by 3.1±1.6 mm in 11 of 19 patients using ADC-ssEPI but not with ADC-rsEPI.nnnCONCLUSIONSnBoth cervix and prostate ssEPI are prone to clinically relevant geometric distortions at 3T. rsEPI provides improved geometric performance without post-processing.

Contemporary Management of Stage I and II Seminoma

Seminoma represents about 60xa0% of all testicular germ cell tumors. At presentation about 80xa0% of patients have stage I and about 15xa0% have stage II disease. The last three decades have seen a substantial change in the philosophy of management with the success of surveillance as a strategy to minimize unnecessary treatment, recognition of the late effects of radiation therapy, and the success of cisplatin-based chemotherapy as curative treatment either in the first-line or salvage setting. Overall, in stage I disease where 80–85xa0% are cured with orchiectomy alone, efforts now are directed at reducing the burden of the disease and its diagnosis on patients with increasing utilization of surveillance and decreased employment of adjuvant therapy. For stage II disease, balancing the relative toxicities of radiation and chemotherapy while avoiding the use of multimodality therapy due to the additive long-term toxicity has become the priority.

Dosimetric feasibility of ablative dose escalated focal monotherapy with MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer

PURPOSEnTo determine the dosimetric feasibility of dose-escalated MRI-guided high-dose-rate brachytherapy (HDR-BT) focal monotherapy for prostate cancer (PCa).nnnMETHODSnIn all patients, GTV was defined with mpMRI, and deformably registered onto post-catheter insertion planning MRI. PTV included the GTV plus 9mm craniocaudal and 5mm in every other direction. In discovery-cohort, plans were obtained for each PTV independently aiming to deliver ⩾16.5Gy/fraction (two fraction schedule) while respecting predefined organs-at-risk (OAR) constraints or halted when achieved equivalent single-dose plan (24Gy). Dosimetric results of original and focal HDR-BT plans were evaluated to develop a planning protocol for the validation-cohort.nnnRESULTSnIn discovery-cohort (20-patients, 32-GTVs): PTV D95% ⩾16.5Gy could not be reached in a single plan (3%) and was accomplished (range 16.5-23.8Gy) in 15 GTVs (47%). Single-dose schedule was feasible in 16 (50%) plans. In the validation-cohort (10-patients, 10-GTVs, two separate implants each): plans met acceptable and ideal criteria in 100% and 43-100% respectively. Migration to single-dose treatment schedule was feasible in 7 implants (35%), without relaxing OARs constraints or increasing the dose (D100% and D35%) to mpMRI-normal prostate (p>0.05).nnnCONCLUSIONnFocal ablative dose-escalated radiation is feasible with the proposed protocol. Prospective studies are warranted to determine the clinical outcomes.

Survival outcomes for cutaneous angiosarcoma of the scalp versus face: Angiosarcoma of scalp and face

The primary purpose of this study was to examine whether angiosarcoma outcomes differ for the scalp and face.

Quality indicators in the management of bladder cancer: A modified Delphi study

BACKGROUNDnSurvival in patients with bladder cancer has only moderately improved over the past 2 decades. A potential reason for this is nonadherence to clinical guidelines and best practice, leading to wide variations in care. Common quality indicators (QIs) are needed to quantify adherence to best practice and provide data for benchmarking and quality improvement.nnnOBJECTIVEnTo produce an evidence- and consensus-based list of QIs for the management of bladder cancer.nnnMETHODSnA modified Delphi method was used to develop the indicator list. Candidate indicators were extracted from the literature and rated by a 27-member Canadian expert panel in several rounds until consensus was reached on the final list of indicators. In rounds with numeric ratings, a frequency analysis was performed.nnnRESULTSnA total of 86 indicators were rated, 52 extracted from the literature and 34 suggested by the panel. After iterative rounds of ratings and discussion, a final list of 60 QIs spanning several disciplines and phases of the cancer care continuum was developed.nnnCONCLUSIONSnThis is the first study to comprehensively produce common QIs representing structure, process, and outcome measures in bladder cancer management. Though developed in Canada, these indicators can be used in other countries with slight modifications to track performance and improve care.

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor

Purpose: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post‐chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy. Materials and Methods: Levels of serum miRNA, including miR‐371a‐3p, miR‐373–3p and miR‐367–3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post‐chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity. Results: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post‐chemotherapy retroperitoneal lymph node dissection specimens. miR‐371a‐3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774–0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR‐371a‐3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02). Conclusions: Our study demonstrates for the first time the potential value of miR‐371a‐3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

Outcome following radiotherapy for head and neck basal cell carcinoma with ‘aggressive’ features

OBJECTIVESnThe literature demonstrates that aggressive head-and-neck basal cell carcinomas (HN-BCC) have a higher than expected relapse rate with unfavorable outcomes. We report outcomes following definitive (dRT) or post-operative radiotherapy (PORT) for these tumors.nnnMETHODSnWe reviewed all HN-BCC patients with aggressive features (primary lesions diameter >10mm, >2 recurrences, or extra-cutaneous extension), treated with megavoltage dRT or PORT between 1998 and 2013. Loco-regional control (LRC) and relapse-free survival (RFS) were estimated using the competing risk method, and overall survival (OS) by Kaplan-Meier method. Univariable analysis explored factors associated with relapse.nnnRESULTSnA total of 108 histologically confirmed aggressive HN-BCC patients were identified, including 38 (35%) presenting de novo and 70 (65%) treated for recurrence (rBCC). dRT was offered to 72 (66.7%) patients and PORT to 36 (33.3%). Median follow-up was 3.5years. Actuarial 3-year LRC, RFS, and OS were 87% (95% confidence interval: 77-92), 82% (72-89), and 87% (80-94), respectively. LRC rates for dRT and PORT were similar [hazard ratio (HR) 0.61 (0.17-2.23), p=0.46]. Factors associated with higher risk of relapse were: rBCC [HR 7.96 (1.03-61.71), p=0.047], H-zone (mid face, eyes, and ears) location [HR 3.13 (1.07-9.19), p=0.04], tumor size [HR 1.32 (1.08-1.6), p=0.006], nodal involvement [HR 3.68 (1.11-12.2), p=0.03] and stage [HR 3.13 (1.19-8.26), p=0.02].nnnCONCLUSIONnRT is an effective treatment for aggressive HN-BCC when used as a definitive modality or as PORT. Non-surgical management with definitive radiotherapy provides an alternative effective option if surgery is not used.

Clinical Characteristics and Outcomes of Late Relapse in Stage I Testicular Seminoma

AIMSnTo identify the characteristics and outcomes associated with late relapse in stage I seminoma.nnnMATERIALS AND METHODSnA retrospective review was carried out of all patients with stage I seminoma managed at our institution between 1981 and 2011. Data were obtained from a prospectively maintained database. Late relapse was defined as tumour recurrence > 2 years after orchiectomy.nnnRESULTSnOverall, 1060 stage I seminoma patients were managed with active surveillance (n=766) or adjuvant radiotherapy (n=294). At a median follow-up of 10.6 years (range 1.2-30), 142 patients relapsed at a median (range) of 14 (3-129) months; 128 on active surveillance and 14 after adjuvant radiotherapy. The late relapse rate for the active surveillance and adjuvant radiotherapy groups was 4% and 1%, respectively. There was no specific clinicopathological factor associated with late relapse. Isolated para-aortic node(s) was the most common relapse site in active surveillance patients either in late (88%) or early relapse (82%). Among the active surveillance group, no patients with late relapse subsequently developed a second relapse after either salvage radiotherapy (n=25) or chemotherapy (n=6), whereas in early relapse patients a second relapse was reported in seven (10%) of 72 patients treated with salvage radiotherapy and one (4%) of 23 patients who received chemotherapy; all second relapses were subsequently salvaged with chemotherapy. No patient in the adjuvant radiotherapy group developed a second relapse after salvage chemotherapy (n=10) or inguinal radiotherapy/surgery (n=4). Of seven deaths, only one was related to seminoma. Among active surveillance patients, the 10 year overall survival for late and early relapse groups were 100% and 96% (Pxa0=xa00.2), whereas the 10 year cancer-specific survival rates were 100% and 99% (Pxa0=xa00.3), respectively.nnnCONCLUSIONSnIn stage I seminoma, the extent and pattern of late relapse is similar to that for early relapse. For active surveillance patients, selective use of salvage radiotherapy/chemotherapy for relapse results in excellent outcomes regardless of the timing of relapse, whereas salvage radiotherapy for late relapse seems to be associated with a minimal risk of second relapse.

Comparison of 3 image-guided adaptive strategies for bladder locoregional radiotherapy

The objective of this study was to compare the dosimetric differences of a population-based planning target volume (PTV) approach and 3 proposed adaptive strategies: plan of the day (POD), patient-specific PTV (PS-PTV), and daily reoptimization (ReOpt). Bladder patients (nu2009=u200910) were planned and treated to 46u2009Gy in 23 fractions with a full bladder in supine position by the standard strategy using a population-based PTV. For each patient, the adaptive strategy was executed retrospectively as follows: (1) POD-multiple distributions of various PTV sizes were generated, and the appropriate distribution based on the bladder of the day was selected for each fraction; (2) PS-PTV-population-based PTV was used for the first 5 fractions and a new PTV derived using information from these fractions was used to deliver the remaining 18 fractions; and (3) ReOpt-distribution was reoptimized for each fraction based on the bladder of the day. Daily dose was computed on all cone beam computed tomographies (CBCTs) and deformed back to the planning computed tomography (CT) for dose summation afterward. V95_Accu, the volume receiving an accumulated delivered dose of 43.7u2009Gy (95% prescription dose), was measured for comparison. Mean V95_Accu (cm3) values were 1410 (standard deviation [SD]: 227), 1212 (SD: 186), 1236 (SD: 199), and 1101 (SD: 180) for standard, POD, PS-PTV, and ReOpt, respectively. All adaptive strategies significantly reduced the irradiated volume, with ReOpt demonstrating the greatest reduction compared with the standard (-u200925%), followed by PS-PTV (-u200916%) and POD (-u200912%). The difference in the magnitude of reduction between ReOpt and the other 2 strategies reached statistical significance (pu2009=u20090.0006). ReOpt is the best adaptive strategy at reducing the irradiated volume because of its frequent adaptation based on the daily geometry of the bladder. The need to adapt only once renders PS-PTV to be the best alternative adaptive strategy.