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  • American Society of Clinical Oncology (ASCO)  (9)
  • Anson-Cartwright, Lynn  (9)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 6 ( 2015-02-20), p. 582-587
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 2_suppl ( 2016-01-10), p. 493-493
    Abstract: 493 Background: Genomic signatures may compliment pathological features in identifying appropriate patients who may benefit from adjuvant therapy in Stage I (SI) TGCT. This study aimed to identify a gene expression pattern to differentiate between relapsed (R) and non-relapsed (NR) SI TGCT. Methods: Patients with SI non-seminoma (NS) and seminoma (S) were identified from an institutional database from 2000 to 2012. All patients were managed with active surveillance. NR-NS and NR-S patients were defined as having no evidence of relapse after 2 and 3 years of surveillance respectively. Following pathology review, RNA extraction and gene expression analysis was performed on archived paraffin embedded tumor and normal testicular tissue using Illumina Whole Genome DASL Human HT-12 V4 BeadChip. Hierarchical clustering analysis, ANOVA and t-tests were used to evaluate candidate genes and expression patterns that could differentiate NR and R samples. Results: 57 patients (12 R-NS, 15 R-S, 15 NR-NS, 15 NR-S) were identified with median relapse time of 5.6 (2.5-18.1) and 19.3 (4.7-65.3) months in NS and S cohorts respectively. 3 additional normal testis samples were included. Poor prognostic factors were more frequent in R versus NR cases (NS: vascular invasion [5/12 vs 0/15]; S: median size [4cm vs 2.8cm] ). Unsupervised hierarchical clustering of 22822 probes randomly separated S from NS, indicating no batch effect. One-way ANOVA revealed 4525 significantly varying probes (p 〈 0.05) however, no statistically significant gene expression profile differentiated the 4 cohorts. A discriminative gene expression profile between R and NR cases was discovered when combining NS and S samples using 10 (p = 0.03) and 30 (p = 0.03) probe signatures with a 10 fold cross-validation. However, this profile was not observed in the S and NS cohorts individually. Conclusions: A discriminating signature for R and NR was identified for SI testis tumors, but not separately for NS and S. Biological relevance of these signatures is to be determined. Further studies are required to corroborate this profile in NS and S. If validated, these expression patterns could help identify patients beyond standard pathological risk algorithms for optimal management.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 22 ( 2019-08-01), p. 1919-1926
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 546-546
    Abstract: 546 Background: Retroperitoneal lymph node dissection (RPLND) is recommended for residual masses 〉 1cm post-chemotherapy (pc) for nonseminomatous germ cell tumors (NSGCT). There is no reliable predictor for pcRPLND histology and up to 50% will harbour necrosis/fibrosis only, thus rendering a potentially morbid surgery to be of limited therapeutic value. Objective: To evaluate the ability of defined serum microRNA (miRNA) using the ampTSmiR test to predict residual viable NSGCT after chemotherapy. Methods: Serum miRNA levels (miR-371a-3p, miR-373-3p and miR-367-3p) were measured in 82 patients (cohort A = 39, cohort B = 43) treated with orchiectomy, chemotherapy and pcRPLND to predict viable GCT post-chemotherapy. Outcomes, measurements and statistical analysis: miRNA levels were compared to clinical characteristics, serum tumor markers and correlated with presence of viable GCT (vs. teratoma; vs. necrosis/fibrosis). miRNA-discriminative capacity was determined by receiver operating characteristic (ROC) analysis. Results: Serum miRNA were associated with stage at the time of chemotherapy and declined significantly post-chemotherapy. Patients with fibrosis/necrosis and teratoma had a significant decline in all three miRNA levels after chemotherapy, while those with viable disease had very little change. Patients with necrosis/fibrosis demonstrated similar miRNA levels as patients with residual teratoma. miR-371a-3p demonstrated the highest discriminative capacity [area under the curve (AUC) 0.874, CI 95% 0.774 - 0.974 p 〈 0.0001] for viable disease post chemotherapy. If considering a more relaxed cut-point of 3cm before consideration of pcRPLND, miR-371a-3p correctly stratified all patients with residual retroperitoneal lesions ≤ 3 cm ( p= 0.02; 100% sensitivity). Conclusions: Our study is the first to explore a miRNA-based serum test to determine histology in post-chemotherapy residual masses and we demonstrated the value of miR-371a-3p to predict presence of viable GCT. Prospective studies are required to confirm its clinical utility.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 377-377
    Abstract: 377 Background: Active surveillance (AS) is universally accepted for clinical stage (CS) IA and favoured by most centers for CSIB. Patients progressing on AS are typically treated with chemotherapy, but there is no consensus. We describe patterns and mode of detection of progression and treatment of progression in our NSGCT AS cohort. Methods: From Dec 1980 to Aug 2011, 466 CSI NSGCT patients were managed with AS and 133 (28%) had disease progression while on AS. Treatment upon progression was physician choice but based on site of progression (e.g. retroperitoneum vs. extra-retroperitoneal), size or multifocality, and markers (S0 or stable, low level S1 vs. ≥ S1). Mode of detection of progression, characteristics at progression and primary treatment of progression (chemotherapy vs. retroperitoneal lymphadenectomy (RPLND)) were explored. Multivariate logistic regression was used to explore factors associated with receipt of more than one therapy in treatment of progression after surveillance. Results: Median time to progression was 7.3 months and detected by routine imaging (47%), routine serum tumour markers (37%), or both (12%). Progression most frequently occurred in the retroperitoneum (67%). Following progression, first-line treatment was chemotherapy for 71 (53%), RPLND for 51 (38%) and 11 (8.3%) underwent other therapy. In 59%, only one modality of treatment was required: chemotherapy only in 42/71 (59%); RPLND only in 36/51 (71%). For those treated with chemotherapy, pure embryonal carcinoma in the orchiectomy pathology (OR 0.11; p=0.05) was inversely associated with requiring further therapy. For those treated with RPLND, elevated markers pre-RPLND (OR 7.31; p=0.01) was associated with requiring further therapy. Overall, a second relapse occurred in 25/133 (19%) patients. With a median follow-up of 8.2 years, there were 5 deaths from testis cancer (3.8% of AS progressors; only 1.1% of overall AS cohort). Conclusions: The majority of patients progressing on surveillance do so in the retroperitoneum and within the first year. Of those that progress, most will achieve complete response with single modality treatment. In particular, RPLND can be utilized as monotherapy in select cases.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4535-4535
    Abstract: 4535 Background: VTE causes substantial morbidity and mortality in GCT pts. The Khorana model is a validated predictive model that stratifies VTE risk in cancer pts receiving chemo; Khorana score ≥3 (K3) identifies pts at high risk. Many GCT pts have bulky RPLN that can cause venous stasis in the lower limbs. This study examines the incidence of VTE in GCT pts and assesses large RPLN as a novel predictor of VTE risk. Methods: Retrospective data from the Princess Margaret Hospital GCT database was complemented by review of medical records. GCT pts receiving 1st line chemo between 2000-2010 were included. Pts diagnosed with VTE prior to chemo and pts receiving thromboprophylaxis (TP) were excluded. Pts diagnosed with VTE during or within 3 months of completing chemo were identified. Large RPLN were defined as having maximal diameter ≥5cm. Odds ratios for VTE risk with large RPLN and K3 were calculated. Discriminatory accuracy (DA) of each predictor was calculated using area under the receiver operating characteristic curves (AUROC). An external cohort from London Regional Cancer Program, with similarly collected data, was used to validate results. Results: In the test cohort 21 (10%) of 216 pts developed VTE. Both large RPLN (OR 6.2, p 〈 0.001) and K3 (OR 11.8, p 〈 0.001) were significantly associated with VTE. Positive predictive value (PPV) was lower for large RPLN compared to K3 (21% v 44%, p 〈 0.014) but sensitivity was greater (71% v 40%, p=0.001), while DA showed no difference (AUROC 0.73 v 0.67, p=0.46). In the validation cohort 10 (9%) of 111 pts developed VTE. There was a non significant trend for associations between VTE and both large RPLN (OR 2.54, p=0.16) and K3 (OR 4.5, p=0.13). When compared to K3, sensitivity was greater for large RPLN (60% v 20%, p=0.003), but there was no difference in PPV (14% v 29%, p=0.25) or DA (AUROC 0.61 v 0.57, p=0.72). Conclusions: VTE occurs in 1 in 10 GCT pts receiving curative chemotherapy. Large RPLN is a novel and clinically applicable predictor of VTE risk, although prospective validation would be beneficial. Randomized controlled trials of TP in GCT pts should be considered in pts at high risk of VTE, identified by large RPLN or K3.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 328-328
    Abstract: 328 Background: Use of GCSF and the development of renal impairment in GCT pts receiving chemo are common, but their effect on toxicity and survival is unclear. This study examines the impact of GCSF and renal impairment on bleo lung, FN and survival, in GCT pts receiving 1st line chemo. Methods: Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy and medical records. All GCT pts receiving 1st line chemo between 1-Jan-00 and 31-Dec-10 were included. Pts receiving at least one GCSF dose were identified. Renal impairment during chemo was defined as any serum creatinine above the institutional upper limit of normal. Bleo lung was graded (G1-5) using CTCAE criteria. FN was defined as temperature ≥38C and neutrophil count 〈 1.0. Results: The cohort consisted of 260 GCT pts, median age 31.5 years, 171 (66%) had IGCCCG good risk disease, 42 (16%) intermediate, and 41 (16%) poor, while 6 (2%) received adjuvant chemo. 159 (61%) received GCSF and 49 (19%) developed renal impairment. 212 (82%) received BEP of which 73 (34%) developed bleo lung (56 pts G1 asymptomatic, 13 pts G2, 4 pts ≥G3). Renal impairment was associated with bleo lung in univariate (OR 2.87, p=0.008) and multivariate (OR 2.69, p=0.01) analyses. GCSF was associated with increasing severity of bleo lung (OR 1.86, p=0.045) but this was not significant in a multivariate analysis (OR 1.72, p=0.08). FN occurred in 33 (13%) of 260 pts. Renal impairment (OR 3.91, p=0.001) was associated with FN. Primary GCSF prophylaxis reduced FN (OR 0.26, p=0.001), however, 8 (7%) of 112 patients developed FN in spite of GCSF prophylaxis. Survival analyses demonstrated GCSF and renal impairment did not impact progression free or overall survival (OS), however, bleo lung was associated with poorer OS in a multivariable Cox proportional hazards analysis (HR 2.85, p=0.029). Conclusions: Our findings demonstrate both renal impairment and GCSF are risk factors for bleo lung, while renal impairment itself is also a risk factor for FN. Additionally, we identify bleo lung as a significant poor prognostic factor for OS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 332-332
    Abstract: 332 Background: VTE causes significant morbidity and mortality in GCT pts. While an existing and validated predictive model identifies VTE risk in chemo pts with any cancer (Khorana model), a predictive model specific to GCT does not exist. Many GCT pts present with bulky RPLN that produce venous stasis in the lower extremities. The objective of this study was to explore the association between large RPLN and VTE in GCT pts receiving chemo and compare large RPLN as a predictor for VTE in GCT pts to the non-GCT specific Khorana model. Methods: Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy and medical records. All GCT pts receiving 1st line chemo between 1-Jan-00 and 31-Dec-10 were included. Large RPLN were defined as ≥5cm in maximal diameter. Factors used in the Khorana model (baseline BMI, hemoglobin, white cell count and platelets) were collected. We compared the predictive accuracy of large RPLN versus Khorana score ≥3 using receiver operator characteristic (ROC) curve statistical analyses. Results: The cohort consisted of 260 GCT pts, median age 31.5 years, predominantly testis primary (235, 90%) and good risk (171, 66%). 17 (7%) developed VTE prior to the start of chemo. 19 (7%) were given prophylactic anticoagulation, none of whom developed VTE. Of the remaining 224 pts, 20 (9%) developed VTE during chemo. In a univariate analysis, large RPLN was strongly associated with VTE (OR 7.74, p 〈 0.001), as were Khorana score ≥3 (OR 9.81, p 〈 0.001) and hospital admission during chemo (OR 3.96, p=0.004). ROC curve analyses demonstrated large RPLN was a significant individual predictor for VTE (AUC 0.588, p=0.03), however, Khorana score ≥3 was a better predictor (AUC 0.664, p=0.02). Adding large RPLN to create a modified Khorana score provided marginal gains (AUC 0.682, p=0.02). Conclusions: Although large RPLN at diagnosis predicts for VTE in GCT pts, the Khorana predictive model is superior. Given the high rate of VTE in GCT pts receiving chemo, we recommend prophylactic anticoagulation for pts at increased risk, including pts with Khorana score ≥3, pts requiring hospital admission or pts with large RPLN.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 4559-4559
    Abstract: 4559 Background: After chemotherapy, 〉 50% of patients (pts) with metastatic testicular GCT who undergo retroperitoneal lymph node dissection (RPNLD) for residual masses are found to have fibrosis (F) alone on pathological examination. To minimize overtreatment, better prediction algorithms are needed to identify pts with F who can avoid RPLND. Radiomics uses image processing techniques to extract quantitative textures/features from tumor regions of interest (ROI) to train a classifier that predicts pathological findings. We hypothesized that radiomics may identify pts with a high predicted likelihood of F who may avoid RPLND. Methods: Pts with GCT who had an RPLND for nodal masses 〉 1cm after first line platinum chemotherapy were included. Preoperative contrast enhanced axial CT images of retroperitoneal ROI were manually contoured. 153 radiomics features trained a radial basis function support vector machine classifier to discriminate between viable GCT /Mature Teratoma (T) vs F. Nested ten-fold cross-validation protocol was employed to determine classifier accuracy. Clinical variables and restricted size criteria were used to optimize the classifier. Results: A total of 82 pts with 102 ROI were analyzed (GCT: 21; T: 41; F: 40). The discriminative accuracy of radiomics to identify GCT/T vs F was 72%(±2.2)(AUC: 0.74 (±0.028); positive predictive value: 67% (48-92%); negative predictive value: 74% (62-84%)(p = 0.001)). No major predictive differences were identified when data was restricted by varying maximal axial diameters (AUC range: 0.58(±0.05) - 0.74(±0.03)). Prediction algorithm using clinical variables alone identified an AUC of 0.71 (±0.15). When these variables were added to the radiomic signature, the best performing classifier was identified when axial tumors were limited to diameter 〈 2cm (accuracy: 88.2 (±4.4); AUC: 0.80 (±0.05)(p = 0.02)). Conclusions: A predictive radiomics algorithm had an overall discriminative accuracy of 72% that improved to 88% when combined with clinical details. Further independent validation is required to assess whether radiomics, in conjunction with standard clinical predictors, may allow pts with a high predicted likelihood of F to avoid RPLND.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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