Mutational Aberrations Detected in Mucinous Epithelial Ovarian Cancer of Asian Women

BackgroundMucinous epithelial ovarian cancers (mEOCs) respond poorly to conventional chemotherapy and have a poor prognosis in advanced stages. The genomic landscape for mEOC in the Asian settings is ill defined. We seek to identify various mutational aberrations present in mEOC and correlate them with clinical outcomes.MethodsA total of 199 cases of mEOC were identified from a prospectively maintained gynecologic oncology tumor database. DNA was extracted and analyzed for KRAS mutations by using Sanger sequencing. Further MassArray sequencing was performed on 45 samples. Clinicopathologic correlation was performed with the results obtained.FindingsKRAS mutation status was evaluable in 124 cases. Fifty-five percent (68/124) were KRAS negative, whereas 45% (56/124) harbored a KRAS mutation, lower than that in Western populations. Successful ascertainment of both KRAS and HER2 statuses by Sanger sequencing occurred for 105 cases. The proportion of the double-positive subtype (HER2+ and KRAS positive) was 8% (8/105); double-negative subtype (HER2− and KRAS negative), 34% (36/105); and cases with mutation in either KRAS or HER2, 58% (61/105). The KRAS mutation rate was 44%, 50%, and 29% among Chinese, Indians, and Malays, respectively. There was no significant difference in overall survival (P = 0.952) or progression-free survival (P = 0.635) between KRAS-positive and KRAS-negative patients. Similar results were observed for progression-free survival (P = 0.206) and overall survival (P = 0.440) when outcomes were examined between the 4 groups based on KRAS and HER2 mutation. Patients in the double-negative mutation subgroup had higher risk for death/progression compared with patients in the other 3 mutation subgroups. Further MassARRAY multiplexed profiling was performed in patients with sufficient DNA material (n = 45) and yielded KRAS mutations (n = 16), PDGFRA mutations (n = 3), PIK3CA (n = 1) and KIT (n = 1), and HRAS, FGFR, MET, and NRAS (n = 1 each).ConclusionsOur study provides further knowledge about the mutational aberrations in mEOC in Asian populations. Neither the presence of KRAS mutation nor their correlation with HER2 mutations influenced outcomes.

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Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02964-x ◽

2021 ◽

Author(s):

Yang Wang ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Objective Response ◽

Progression Free Survival ◽

Meaningful Improvement ◽

Free Survival ◽

Significant Difference ◽

Grade 3 ◽

Doublet Chemotherapy ◽

Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

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Are Hormonal Agents Better Than Chemo İn Metastati̇c Castrati̇on Resistant Prostate Cancer?

10.21203/rs.3.rs-199255/v1 ◽

2021 ◽

Author(s):

Serkan Yıldırım ◽

Atike Pınar ERDOĞAN ◽

Cengiz Yılmaz ◽

Ferhat Ekinci ◽

Gülcan Bulut ◽

...

Keyword(s):

Overall Survival ◽

Therapy Group ◽

Hormonal Treatment ◽

Progression Free Survival ◽

Free Survival ◽

Chemotherapy Group ◽

Randomized Controlled Studies ◽

Significant Difference ◽

Hormonal Therapies ◽

Multi Center Study

Abstract İNTRODUCTİONIn this study, we aim to determine which treatment is more appropriate in castration-resistant chemotherapy-naive patients. Therefore, docetaxel and agents active in the androgen pathway (abiraterone and enzalutamide) were compared retrospectively in patients progressing on ADT.MATERİAL METHODThe study was designed as a retrospective and multi-center study. Patients from 5 centers in Turkey were included in the study. The primary endpoint of the study was ovreall survival and the secondary endpoint was progression-free survival.RESULTSMedian overall survival of the chemotherapy group was 18.66 months, it was 16.26 months in the hormonal treatment group. There was no statistically significant difference between the groups (p = 0.311). Median progression-free survival of the chemotherapy group was 5.6 months, while it was 9 months in the hormonal therapy group. There was statistically significant difference between the groups (p = 0.024).CONCLUSİONThere was statistical difference in progression-free survival in favor of hormonal therapies in our study. The difference did not reflect on overall survival and there was no difference between hormonal therapies and docetaxel. Heterogeneity in the selection of patients is considered to lead to this result; however, larger randomized controlled studies are needed to determine the most appropriate treatment in these patients.

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Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma

Clinical Chemistry ◽

10.1373/clinchem.2017.283721 ◽

2018 ◽

Vol 64 (4) ◽

pp. 726-734 ◽

Cited By ~ 21

Author(s):

Min Kyeong Kim ◽

Sang Myung Woo ◽

Boram Park ◽

Kyong-Ah Yoon ◽

Yun-Hee Kim ◽

...

Keyword(s):

Kras Mutation ◽

Progression Free Survival ◽

Ductal Adenocarcinoma ◽

Multiplex Detection ◽

Kras Mutations ◽

Cell Free Dna ◽

Free Survival ◽

Free Dna ◽

Fractional Abundance ◽

Prognostic Implications

Abstract BACKGROUND Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20–3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02–2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05–3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. CONCLUSIONS This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.

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EPID-07. HEMATOLOGICAL ADVERSE EVENTS IN GLIOBLASTOMA PATIENTS TREATED WITH TEMOZOLOMIDE

Neuro-Oncology ◽

10.1093/neuonc/noz175.307 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi75-vi76

Author(s):

Catherine Garcia ◽

Zin Myint ◽

Rani Jayswal ◽

Allison Butts ◽

Heidi Weiss ◽

...

Keyword(s):

Overall Survival ◽

Adverse Events ◽

Protective Factor ◽

Significant Proportion ◽

Progression Free Survival ◽

Free Survival ◽

Significant Difference ◽

History Of ◽

Grade 3 ◽

Severe Grade

Abstract BACKGROUND Temozolomide (TMZ) is the cornerstone for glioblastoma (GBM) treatment. A significant proportion of patients develops hematologic toxicities with limited investigations on outcomes and risk factors for their development. METHODS Our study combines data from the two largest group trials, RTOG 0525 and RTOG 0825, to analyze serious hematologic adverse events (HAE) associated with TMZ therapy for GBM. We analyzed frequency and outcomes of HAE during chemoradiation. RESULTS 1154 patients were evaluated with a median age of 57 years. Over 79% of patients developed HAE during the entire course of GBM treatment. During chemoradiation the most common HAE during chemoradiation was lymphopenia (41.5%), followed by thrombocytopenia (39.0%), and anemia (35.3%). Of these, 34.1% were severe (Grade 3 or 4) and 65.9% were mild (grade 1 or 2). During maintenance the most common HAE was leukopenia (50.7%), followed by neutropenia (50.4%), and lymphopenia (45.3%). MGMT methylation was not associated with HAEs. A history of HAEs during chemoradiation was a protective factor for developing HAEs during maintenance. MGMT methylated and age younger than 50 were protective factors for mortality. Patients that presented HAEs anytime during treatment had a longer overall survival and progression free survival. There was no significant difference in survival between mild or severe HAEs. CONCLUSION HAE are common during chemoradiation with TMZ for GBM, but are more commonly grade 1 or 2 per CTCAE. HAE during GBM treatment is associated with decreased progression free survival and overall survival.

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Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1087 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1087-1087

Author(s):

Zhongsheng Tong ◽

Shufen Li ◽

Yehui Shi ◽

Xu Wang ◽

Chen Wang ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Response Rate ◽

Metastatic Breast ◽

Progression Free Survival ◽

Phase Iii ◽

First Line ◽

Free Survival ◽

Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

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Is RECIST-defined progression free-survival a meaningful endpoint in the era of immunotherapy?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.488 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 488-488 ◽

Cited By ~ 2

Author(s):

Sukhvinder Johal ◽

Irene Santi ◽

Justin Doan ◽

Saby George

Keyword(s):

Overall Survival ◽

Disease Progression ◽

Tumor Regression ◽

Progression Free Survival ◽

Phase Iii ◽

Rank Test ◽

Apparent Lack ◽

Free Survival ◽

Treatment Beyond Progression ◽

Significant Difference

488 Background: Progression-free survival (PFS) is often used as a primary endpoint in oncology clinical trials as a surrogate for overall survival. Traditionally, the Response Evaluation Criteria in Solid Tumors (RECIST) have defined disease progression as a significant increase in the size of tumor lesions and the development of new lesions. However, some patients starting immunotherapy have shown initial increased size of tumor lesions followed by tumor regression, due to the unique mechanism of action of immunotherapies. This initial “pseudo-progression” could be classified inaccurately as disease progression, as evidenced by benefit from the treatment beyond progression approach ( JAMA Oncol 2016). The phase III CheckMate 025 trial of nivolumab versus everolimus in patients with advanced renal cell carcinoma allowed treatment beyond progression if there was investigator-assessed clinical benefit and tolerability. The purpose of our study was to test if treatment duration for an immunotherapy was different from RECIST-defined PFS, and as such, could potentially explain the apparent lack of correlation between RECIST progression and overall survival shown in CheckMate 025. Methods: Using 1-year data from CheckMate 025, Kaplan–Meier methodology was used to estimate the median duration of PFS and time to treatment discontinuation (TTD). Stratified log-rank test was used to assess the difference in treatments. Results: For all patients, the median PFS with nivolumab was 4.6 months (95% CI, 3.7–5.4 months) and median TTD was 6.2 months (95% CI, 5.6–7.7 months). For everolimus, the median PFS was 4.4 months (95% CI, 3.7–5.5 months) and median TTD was 3.9 months (95% CI, 3.7–4.6 months). Conclusions: Patients in CheckMate 025 had significantly longer survival with nivolumab than with everolimus, but with similar PFS. Our analysis demonstrated that while PFS was similar to TTD with everolimus, there was a significant difference between the 2 measures for nivolumab, suggesting that RECIST-defined PFS may not be the proper endpoint to define progression for immunotherapies. Further evaluation of the association of TTD and other immune-related progression endpoints with overall survival is warranted. Clinical trial information: NCT01668784.

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Influences of Uterine Adenomyosis on Muscle Invasion and Prognosis of Endometrioid Adenocarcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000243 ◽

2014 ◽

Vol 24 (8) ◽

pp. 1429-1433 ◽

Cited By ~ 17

Author(s):

Akiyo Taneichi ◽

Hiroyuki Fujiwara ◽

Yoshifumi Takahashi ◽

Yuji Takei ◽

Shizuo Machida ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Progression Free Survival ◽

Stage I ◽

Endometrioid Adenocarcinoma ◽

Free Survival ◽

Histopathological Grade ◽

Significant Difference ◽

Uterine Adenomyosis ◽

Muscle Invasion

ObjectiveEndometrial cancer often coexists with uterine adenomyosis. However, little is known about the clinical characteristics of these cases. Thus, cases of endometrial cancer occurring with and without uterine adenomyosis were compared, and the influences of uterine adenomyosis on the clinical progress of endometrial cancer were examined.Materials and MethodsOf endometrial cancer patients who underwent hysterectomies in our facility from 2002 to 2011, we included only endometrioid adenocarcinoma patients in our study. The patients were divided into 2 groups, adenomyosis group and nonadenomyosis group, according to the presence/absence of uterine adenomyosis. Patient characteristics, stage, histopathological grade, muscle invasion, recurrence, and mortality were retrospectively compared and examined.ResultsThere were 362 cases of endometrioid adenocarcinoma of the uterine body, of which 121 (33.4%) and 241 cases (66.6%) were in the adenomyosis and nonadenomyosis group, respectively. There were no significant differences with respect to the disease stages or ratios of the histopathological grade between the 2 groups. In the adenomyosis group/nonadenomyosis group, 5-year progression-free survival for International Federation of Gynecology and Obstetrics (FIGO) stages I and II was 89.9%/93.7% and that for stages III and IV was 70.6%/62.0%; the 5-year overall survival was 100%/95.9% for FIGO stages I and II, and 88.0%/73.5% for stages III and IV. There were no significant between-group differences for either progression-free survival or overall survival. When limiting the results to only FIGO stage I endometrioid adenocarcinoma, despite no grade variance between the 2 groups, a significant difference was observed in the ratios of outer-half muscle invasion between the adenomyosis and nonadenomyosis groups (19.5% [17/87] vs 10.1% [16/158], P < 0.05); however, the prognosis was similar in the 2 groups.ConclusionsUterine adenomyosis is associated with deep myometrial invasion in stage I endometrioid adenocarcinoma; however, it did not affect the recurrence or mortality rates.

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A pragmatic diagnostic approach to primary intracranial germ cell tumors and their treatment outcomes

CNS Oncology ◽

10.2217/cns-2021-0012 ◽

2021 ◽

Vol 10 (4) ◽

Author(s):

Jeyaanth Venkatasai ◽

Rajesh Balakrishnan ◽

Balakrishnan Rajkrishna ◽

Patricia Sebastain ◽

Rikki Rorima John ◽

...

Keyword(s):

Overall Survival ◽

Germ Cell ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Cell Tumor ◽

Distinct Entity ◽

Intracranial Germ Cell Tumor ◽

Free Survival ◽

Intracranial Germ Cell Tumors ◽

Significant Difference

Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

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SURG-29. LASER INTERSTITIAL THERMAL THERAPY COMPARED TO CRANIOTOMY FOR TREATMENT OF RECURRENT GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.1029 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi245-vi245

Author(s):

Ali Palejwala ◽

Kyle O’connor ◽

Chad Glenn ◽

Michael Sughrue

Keyword(s):

Overall Survival ◽

Adjuvant Therapy ◽

Perioperative Complications ◽

Progression Free Survival ◽

Senior Author ◽

Thermal Therapy ◽

Free Survival ◽

Laser Interstitial Thermal Therapy ◽

Significant Difference ◽

Recurrent Gbm

Abstract There have been publications that propose the use of laser interstitial thermal therapy (LITT) as a viable alternative to craniotomy for the treatment of glioblastoma (GBM). The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for patients with recurrent GBM. To adequately match the cohorts, we included only pre-treatment tumor volumes of under 15 cc. We retrospectively collected data on all patients presenting with recurrent GBM, with a recurrence volume under 15 cc. These patients were either treated with LITT or craniotomy by the senior author. Data included demographics, tumor location and volume, tumor markers, perioperative complications, re-initiation of adjuvant chemotherapy, and long-term follow up data. We performed 23 LITT treatments and 34 craniotomies for recurrent GBM in patients that met selection criteria. There was no significant difference in the patients’ age, tumor volume (6.38 for craniotomy versus 5.765 cc for LITT), location, and post-procedure KPS. Patients that underwent LITT had significantly reduced inpatient stays in comparison to craniotomy (1.7 versus 4.2 days). They also had less perioperative complications (13.0% versus 32.3% for craniotomy). It was found that 28 out of the 34 patients that underwent craniotomy were able to undergo adjuvant therapy; in comparison, 15 out of the 23 patients who underwent LITT had undergone adjuvant therapy. Of these patient’s that underwent adjuvant therapy, 87% of patients were able to receive bevacizumab or a clinical trial versus 42% after craniotomy. Progression-free survival (PFS) and overall survival (OS) after procedure were similar for LITT versus craniotomy, respectively: % PFS-survival at 6 months = 23.5% versus 21.7%. Overall survival did not significantly differ at 9 months versus 9.9 months respectively. LITT appears to be safe and may be as efficacious as craniotomy in achieving progression free survival for small to moderate volume recurrent GBM.

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