MPC-6 Clinical significance of whole chromosomal aberration signatures in non-metastatic medulloblastomas treated with 18Gy of craniospinal irradiation

Abstract Background: One of the most significant challenges is a reduction in the dose of craniospinal irradiation (CSI) in patients with medulloblastoma to minimize neurological sequelae. However, a North American clinical trial failed to show the prognostic non-inferiority of lower-dose irradiation compared to that associated with standard-dose radiation therapy for non-metastatic medulloblastomas. A European retrospective study revealed that whole chromosomal aberration signatures (WCASs) are a potential prognostic factor in Group 3/4 medulloblastoma without metastasis, but whether the molecular signature has the same clinical impact in patients treated with lower-dose CSI remains unknown. Methods: We conducted DNA methylation analysis using an Illumina Infinium Human Methylation EPIC BeadChip array to investigate molecular prognostic markers in 23 medulloblastoma patients who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with lower-dose CSI relative to standard treatment. A WCAS was defined as the presence of at least two of three chromosomal changes as follows: chromosome (chr) 7 gain, chr 8 loss, and chr 11 gain.Results: All patients presented with no residue or a residual tumor smaller than 1.5 cm2 after surgery without metastasis. The median age at onset was 6.9 years, and the median follow-up period was 80.6 months. CSI was delivered at a median dose of 18.0 Gy. Regarding molecular subgrouping, there were 5 WNT, 2 SHH, 1 Group 3, and 15 Group 4 medulloblastomas. Seven patients with Group 3/4 medulloblastomas showed WCASs and had significantly better prognosis than those without the alteration (5-year progression-free survival 100% vs. 63%, p = 0.046). Two late relapses occurred at 89 and 115 months after diagnosis, respectively, and one of these patients presented with a WCAS.Conclusion: WCAS may be a molecular prognostic marker not only in patients with medulloblastoma treated with standard-dose CSI but also in those treated with lower-dose irradiation.

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Bridging the treatment gap in infant medulloblastoma: molecularly informed outcomes of a globally feasible regimen

Neuro-Oncology ◽

10.1093/neuonc/noaa122 ◽

2020 ◽

Vol 22 (12) ◽

pp. 1873-1881

Author(s):

Lorena V Baroni ◽

Claudia Sampor ◽

Adriana Gonzalez ◽

Fabiana Lubieniecki ◽

Gabriela Lamas ◽

...

Keyword(s):

High Risk ◽

Sonic Hedgehog ◽

Progression Free Survival ◽

Craniospinal Irradiation ◽

Mild Intellectual Disability ◽

Free Survival ◽

Entire Cohort ◽

Craniospinal Radiation ◽

Molecular Correlation ◽

Group 3

Abstract Background Infant medulloblastoma represents an enormous challenge in neuro-oncology, due to their simultaneous high-risk of recurrence and high risk of severe neurodevelopmental sequelae with craniospinal irradiation. Currently infant medulloblastoma are treated with intensified protocols, either comprising intraventricular methotrexate or autologous transplant, both of which carry significant morbidity and are not feasible in the majority of the world. We sought to evaluate the molecular predictors of outcome in a cohort of infants homogeneously treated with induction chemotherapy, focal radiation and maintenance chemotherapy. Methods In a retrospective analysis, 29 young children treated with a craniospinal irradiation sparing strategy from Hospital Garrahan in Buenos Aires were profiled using Illumina HumanMethylationEPIC arrays, and correlated with survival. Results Twenty-nine children (range, 0.3–4.6 y) were identified, comprising 17 sonic hedgehog (SHH), 10 Group 3/4, and 2 non-medulloblastomas. Progression-free survival (PFS) across the entire cohort was 0.704 (95% CI: 0.551–0.899). Analysis by t-distributed stochastic neighbor embedding revealed 3 predominant groups, SHHβ, SHHγ, and Group 3. Survival by subtype was highly prognostic with SHHγ having an excellent 5-year PFS of 100% (95% CI: 0.633–1) and SHHβ having a PFS of 0.56 (95% CI: 0.42–1). Group 3 had a PFS of 0.50 (95% CI: 0.25–1). Assessment of neurocognitive outcome was performed in 11 patients; the majority of survivors fell within the low average to mild intellectual disability, with a median IQ of 73.5. Conclusions We report a globally feasible and effective strategy avoiding craniospinal radiation in the treatment of infant medulloblastoma, including a robust molecular correlation along with neurocognitive outcomes.

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NI-19 Use of 11C-methionine PET for decision of discontinuation of adjuvant chemotherapy with temozolomide

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.062 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii14-ii14

Author(s):

Takaaki Beppu ◽

Yuichi Sato ◽

Toshiaki Sasaki ◽

Kazunori Terasaki ◽

Kuniaki Ogasawara

Keyword(s):

Adjuvant Chemotherapy ◽

Small Sample Size ◽

Standardized Uptake Value ◽

Progression Free Survival ◽

Residual Tumor ◽

Small Sample ◽

Tumor Type ◽

Diffuse Astrocytoma ◽

Significant Difference ◽

Met Pet

Abstract Background: The aim was to clarify whether positron emission tomography with 11C-methyl-L-methionine (met-PET) is useful to decide on discontinuation of TMZ-adjuvant therapy in patients with residual diffuse astrocytic tumor. Methods: Subjects were 44 patients with residual tumor comprising 17 with IDH1-mutant diffuse astrocytoma (DA), 13 with IDH1-mutant anaplastic astrocytoma (AA), and 14 with IDH1-wild glioblastoma (GB). All patients received TMZ-adjuvant chemotherapy (median, 12 courses), and whether to discontinue or continue TMZ-adjuvant chemotherapy was decided on the basis of the tumor-to-normal ratio in standardized uptake value from met-PET (T/N); patients with T/N < 1.6 immediately discontinued TMZ, and patients with T/N > 1.6 were either to continued or discontinued TMZ. Progression-free survival (PFS) was compared between patients with T/N > 1.6 and T/N < 1.6 in each tumor type. Median observation period was 434 days after met-PET scanning. Results: The number of patient who underwent recurrence was 10 in DA, 7 in AA, and 11 in GB. All patients showing T/N > 1.6 underwent tumor recurrence. PFS was significantly longer in patients with T/N < 1.6 than T/N > 1.6 in DA and AA (p < 0.01 in both types), but was no significant difference between 2 groups in GB (p = 0.06). Sixteen of 17 patients (94%) in DA and AA showed recurrence from residual tumor, whereas 4 of 11 patients (36%) in GB showed recurrent tumor at remote regions which were different from residual tumor. Conclusions: The present study suggested that met-PET is beneficial to decide to discontinue adjuvant chemotherapy with TMZ in patients with residual tumors of DA and AA, but not useful for patients with GB. Reasons for unsuccessful results in GB might have been small sample size, failure of establishing the cut off value in T/N, recurrences at remote regions where not be assessed by met-PET.

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Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0177 ◽

2016 ◽

Vol 397 (12) ◽

pp. 1265-1276 ◽

Cited By ~ 14

Author(s):

Nancy Ahmed ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Enken Drecoll ◽

Matthias Kotzsch ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Marker ◽

Residual Tumor ◽

Mrna Levels ◽

Serous Ovarian Cancer ◽

Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

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Telomerase Expression Predicts Unfavorable Outcome in Osteosarcoma

Journal of Clinical Oncology ◽

10.1200/jco.2004.03.043 ◽

2004 ◽

Vol 22 (18) ◽

pp. 3790-3797 ◽

Cited By ~ 70

Author(s):

Robert P. Sanders ◽

Rachid Drissi ◽

Catherine A. Billups ◽

Najat C. Daw ◽

Marcus B. Valentine ◽

...

Keyword(s):

Mrna Expression ◽

Primary Tumor ◽

Progression Free Survival ◽

Outcome Analysis ◽

Negative Group ◽

Primary Tumors ◽

Free Survival ◽

Positive Group ◽

Alternative Lengthening ◽

Group 3

Purpose Osteosarcoma is distinct from most cancers in that the majority of osteosarcomas lack telomerase expression and use the alternative lengthening of telomeres (ALT) mechanism to maintain telomeres. Laboratory studies suggest that compared with ALT, telomerase expression is associated with increased tumor aggressiveness. We evaluated the clinical significance of telomerase expression in human osteosarcoma. Patients and Methods Fifty-six osteosarcomas from 51 patients treated at St Jude Children's Research Hospital between 1982 and 2003 were evaluated for telomerase enzyme activity, mRNA expression of the catalytic component of telomerase (TERT), and presence of the ALT pathway. Results Outcome analysis was based on TERT mRNA expression in the primary tumor samples from 44 patients. Fourteen primary tumors expressed TERT mRNA (32%; eight TERT only, six TERT and ALT) and 30 did not express TERT mRNA (68%; 29 ALT, one no ALT). Progression-free survival (PFS) was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 21.4% ± 9.5% v 63.7% ± 11.1%; P = .014). Likewise, overall survival was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 42.9% ± 12.2% v 70.0% ± 9.9%; P = .031). Among 31 patients with nonmetastatic disease at diagnosis, PFS was lower in the TERT-positive group compared with the TERT-negative group (3-year estimates, 33.3% ± 13.6% v 72.0% ± 11.5%; P = .092). Conclusion Telomerase expression in primary tumor samples is associated with decreased PFS and OS in patients with osteosarcoma. Additional studies are warranted to better define the clinical utility of this molecular marker.

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CTIM-14. RANDOMIZED PHASE II OPEN LABEL STUDY OF NIVOLUMAB PLUS STANDARD DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM). NIVOLUMAB BENEFITS OLDER POPULATION

Neuro-Oncology ◽

10.1093/neuonc/noab196.206 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi52-vi52

Author(s):

Manmeet Ahluwalia ◽

David Peereboom ◽

Yasmeen Rauf ◽

Patrick Wen ◽

David Reardon

Keyword(s):

Overall Survival ◽

Low Dose ◽

Standard Dose ◽

Performance Status ◽

Methylation Status ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Dose Effect ◽

Open Label ◽

Anti Vegf

Abstract BACKGROUND Approaches using anti-PD1 therapy alone in rGBM is of limited efficacy. VEGF is upregulated proangiogenic growth factor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. METHODS 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. RESULTS 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall Survival was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p=0.14), while OS was better for arm A in age > 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P=0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P=0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab seem to benefit patients older than 60 years old.

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Abstract 69: Distinct Grouping of Systolic Blood Pressure Trajectories During the First 24 Hours After Stroke Admission and Their Outcomes

Stroke ◽

10.1161/str.48.suppl_1.69 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Beom Joon Kim ◽

Moon-Ku Han ◽

Yong-Jin Cho ◽

Keun-Sik Hong ◽

Jun Lee ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Systolic Blood Pressure ◽

Age At Onset ◽

Stroke Patients ◽

Vascular Events ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Background: Blood pressure of ischemic stroke patients is a potentially modifiable clinical prognostic factor during acute period. However, BP changes dynamically over time and its temporal variation during acute stage has not received much attention. Methods: From a total of 3795 acute ischemic stroke patients who arrived within 24 hours after onset, we selected 2723 eligible patients who had more than 5 systolic blood pressure (SBP) measurements during 24 hours after arrival. To predict group SBPs for 8 time-points during the first 24 hours, a measured SBP reading was imputed to the nearest missing point. Trajectory grouping of acute stroke patients was estimated using PROC TRAJ, with delta BIC and prespecified modeling parameters. Early neurological deterioration (END) was captured during admission and recurrent vascular events was collected through a structured telephone interview at 1 years after. Results: Of the included cases, mean age at onset was 68 ± 13 year-old. NIHSS score at arrival was median 4 [2, 10] and recanalization treatment was done in 598 (22%). Hypertension was diagnosed in 1930 (71%). Based on 48,445 SBP readings during the first 24 hours after arrival, stroke cases were grouped into 5 distinct SBP trajectories as shown in the Figure: Group 1 (low BP), 17%; Group 2 (stable BP), 41%; Group 3 (rapidly stabilized SBP), 11%; Group 4 (higher SBP), 23%; Group 5 (extremely high SBP without stabilization), 8%. Trajectory grouping was independently associated with END and recurrent vascular events (see Figure). Group 1 had low odds of having END (adjusted OR [95% CI]; 0.62 [0.44-0.87], but Group 4 and 5 showed higher probability of having END (1.34 [1.04-1.73] and 1.76 [1.22-2.51]) and recurrent vascular events until 1 year (1.28 [1.00-1.64] and 1.82 [1.29-2.55]). However, Group 3 had comparable risks with Group 2. Conclusion: It was documented that SBP may successfully grouped into distinct trajectories, which are associated with outcomes after stroke.

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High Anti-Müllerian Hormone Level is Associated with A Lower Chromosomal Aberration Rate in Miscarried Conceptus From Women with Early Spontaneous Abortion

10.21203/rs.3.rs-40240/v1 ◽

2020 ◽

Author(s):

Mingkun Mu ◽

Simin Sun ◽

Wei Zheng ◽

Chen Yang ◽

Shuheng Yang ◽

...

Keyword(s):

Spontaneous Abortion ◽

Chromosomal Aberration ◽

Chromosomal Abnormalities ◽

Clinical History ◽

Advanced Age ◽

Gene Testing ◽

Significant Difference ◽

Number Variation ◽

Group 3 ◽

Group 2

Abstract Background: Approximately 10-15% of clinically recognized pregnancies end in abortion. Most miscarriages occur as early spontaneous abortions. There are many factors leading to early spontaneous abortion, and 50–60% of such cases are associated with chromosomal abnormalities. The reason for this occurrence is not clear, but advanced age is a risk factor for chromosomal aberration in miscarried conceptus from women with early spontaneous abortion. As a marker of ovarian reserve, anti-Müllerian hormone (AMH) is negatively correlated with age. As women become older, AMH levels decrease. The objective of this study was to investigate whether different anti-Müllerian hormone (AMH) levels are associated with chromosomal aberration rate in miscarried conceptus from women who experience early spontaneous abortion.Methods: We collected the clinical history and miscarried conceptus of 434 women with early spontaneous abortion from January 2016 to June 2019. The women were divided into three groups according to AMH level (Group 1: low AMH <1.1 ng/ml [N =13], Group 2: normal AMH 1.1–4.5 ng/ml [N = 138], and Group 3: high AMH≥4.5 ng/ml [N =283]). Clinical history included age, anti-Müllerian hormone (AMH) level, number of previous abortions, estradiol (E2) level, luteinizing hormone (LH) level, follicle-stimulating hormone (FSH) level, infertile years, body mass index (BMI) and infertility factors. The miscarried conceptus was submitted for chromosomal copy number variation (CNV) analysis in the gene testing laboratory of the Third Affiliated Hospital of Zhengzhou University. Results: There were significant differences in age (39.5±4.3 vs. 33.0±5.3v s. 29.7±3.9, P＜0.001), E2 (187.9±513.4 vs. 92.9±160.6 vs. 66.5±139.3, P=0.019), LH (5.1±3.9 vs. 4.5±2.5 vs. 5.4±3.5, P=0.039), and FSH (10.7±5.6 vs. 7.3±2.6 vs. 6.4±2.1, P＜0.001) in different AMH groups. There were no significant differences in infertility years, BMI and infertility factors among the three groups.There was a significant difference in chromosomal aberration rate between different AMH groups (76.9% vs. 67.4% vs. 53.7%, Groups 2 vs. 3, respectively, P=0.008, OR 0.797, 95% CI 0.680-0.934). With the increase in AMH level, the chromosomal aberration rate in miscarried conceptus decreased gradually. After age stratification, the chromosomal aberration rate in miscarried conceptus was still significantly different among AMH groups, with a similar trend in women ≥35 years old (88.9% versus 76.0% versus 51.5%, P2 vs. 3 = 0.021, OR 0.678, 95% CI 0.470-0.977). There was the same trend in the younger group (＜35 years), but there was no significant difference (88.9% vs. 76.0% vs. 51.5).Conclusions: These findings indicate that high AMH level was associated with reduced risk of chromosomal aberration rate, especially in women of advanced age (≥35 years).

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NIMG-06. OUR THERAPEUTIC STRATEGIES FOR GLIOBLASTOMA: INTRAOPERATIVE SUPPORT SYSTEMS [INTRAOPERATIVE MRI, PET, 5-AMINOLEVULINIC ACID (5-ALA)] AND NEOADJUVANT CHEMOTHERAPY

Neuro-Oncology ◽

10.1093/neuonc/noz175.678 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi162-vi162

Author(s):

Keisuke Miyake ◽

Daisuke Ogawa ◽

Masaki Okada ◽

Tetsuhiro Hatakeyama ◽

Takashi Tamiya

Keyword(s):

Pet Imaging ◽

Aminolevulinic Acid ◽

Performance Status ◽

Progression Free Survival ◽

Residual Tumor ◽

Extraction Rate ◽

Intraoperative Mri ◽

Positron Emission ◽

Magnetic Resonance Imaging Mri ◽

Tumor Extraction

Abstract OBJECTIVE Neuronavigation systems with magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging (methionine [MET], fluorothymidine [FLT], and fluoromisonidazole [FMISO]) are routinely used in glioblastoma surgery. Residual tumor identified using intraoperative MRI (IoMRI) or 5-aminolevulinic acid (5-ALA) fluorescence is removed. Neoadjuvant bevacizumab therapy is offered to patients with low Karnovsky performance status (KPS) or with tumors in eloquent regions. We evaluated the usefulness of neoadjuvant bevacizumab therapy. METHODS Twelve patients with glioblastoma with low KPS or tumors in eloquent regions on multiple PET and IoMRI evaluations were enrolled between January 2016 and April 2019. Six had received neoadjuvant bevacizumab before surgery; six had not. Postsurgical 5-ALA fluorescence (strong, vague, and none) tumor extraction rate, residual volume on MRI and PET imaging, and prognosis in the patients with and without bevacizumab were compared. RESULTS In patients with bevacizumab adjuvant therapy, the KPS scores immediately prior to surgery were 90 in 3 cases, 80 in 2, and 70 in 1. The scores in patients without bevacizumab were 50 in 2 and 40 in 4. The 5-ALA fluorescence in patients with bevacizumab was vague in one and none in five. Vague fluorescence was noted in all six patients without bevacizumab. Tumor extraction rates in patients with vs. those without bevacizumab were 97.6% vs. 91.5% by T1-Gd, 95.4% vs. 99.9% by MET, 96.2% vs. 90.2% by FLT, and 97% vs. 92% by FMISO. Corresponding residual volumes (ml) were (0.6 vs. 1.7) for T1-Gd, 1.2 vs. 2.9 for MET, 1.0 vs. 2.1 for FLT, and 0.5 vs. 1.1 for. FLT. Median progression free survival (PFS) was 10.1 vs. 4.9 months; median overall survival (OS) was 15.7 vs. 13.3 months. CONCLUSIONS Neoadjuvant bevacizumab therapy improved KPS at the time of surgery, increased extraction rate, reduced residual tumor volume, and improved PFS and OS prognosis.

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Randomized trial comparing two combination chemotherapy regimens (CHAP-5 v CP) in advanced ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.8.1157 ◽

1987 ◽

Vol 5 (8) ◽

pp. 1157-1168 ◽

Cited By ~ 190

Author(s):

J P Neijt ◽

W W ten Bokkel Huinink ◽

M E van der Burg ◽

A T van Oosterom ◽

P H Willemse ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Stage Iv ◽

Progression Free Survival ◽

Therapeutic Index ◽

Residual Tumor ◽

Figo Stage ◽

Gynecology And Obstetrics ◽

Adequate Hydration ◽

Karnofsky Index

One hundred ninety-one patients with advanced epithelial ovarian carcinoma were treated with either a combination of doxorubicin and a five-day course of cisplatin alternating with cyclophosphamide and hexamethylmelamine orally for 14 days (CHAP-5) or cyclophosphamide and cisplatin both administered intravenously (IV) on a single day at 3-week intervals (CP). At a median follow-up time of 45 months, treatment with each of these combinations resulted in the same remission rates (80% and 74%, respectively) and exactly the same progression-free survival and overall survival (median, 26 months). Despite adequate hydration, more renal toxicity was encountered in the CP-treated patients than in those who received CHAP-5. Disabling neurotoxicity and severe myelosuppression were encountered more frequently in the patients treated with CHAP-5. Because the toxicity was lower and CP treatment required shorter hospitalization, the single-day regimen was considered preferable for future use. The Karnofsky index was the only independent predictor for response, whereas both this index and the size of residual tumor before chemotherapy were predictive of survival. After correcting for other prognostic factors, it was determined that tumor size associated with improved survival was less than 1 cm. The site of metastases in International Federation of Gynecology and Obstetrics (FIGO) stage IV patients did not influence survival within this category. The results of this study confirm our previous findings that patients with microscopic remnants at second-look have a survival similar to that of patients who are histopathologically free of disease. This makes the significance of so-called pathologically confirmed complete remission questionable. The survival benefit of debulking surgery performed during chemotherapy seems only minimal for patients in whom debulking has already been attempted before treatment. Like others, we have found the CP regimen to have a good therapeutic index.

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Determining the utility of intraoperative magnetic resonance imaging for transsphenoidal surgery: a retrospective study

Journal of Neurosurgery ◽

10.3171/2013.9.jns122207 ◽

2014 ◽

Vol 120 (2) ◽

pp. 346-356 ◽

Cited By ~ 30

Author(s):

Jan Coburger ◽

Ralph König ◽

Klaus Seitz ◽

Ute Bäzner ◽

Christian Rainer Wirtz ◽

...

Keyword(s):

Transsphenoidal Surgery ◽

High Field ◽

Progression Free Survival ◽

Residual Tumor ◽

Conventional Group ◽

Free Survival ◽

Kaplan Meier ◽

Remission Rates ◽

Biochemical Remission

Object Intraoperative MRI (iMRI) provides updated information for neuronavigational purposes and assessments on the status of resection during transsphenoidal surgery (TSS). The high-field technique additionally provides information about vascular structures at risk and precise information about extrasellar residual tumor, making it readily available during the procedure. The imaging, however, extends the duration of surgery. To evaluate the benefit of this technique, the authors conducted a retrospective study to compare postoperative outcome and residual tumor in patients who underwent conventional microsurgical TSS with and without iMRI. Methods A total of 143 patients were assessed. A cohort of 67 patients who had undergone surgery before introduction of iMRI was compared with 76 patients who had undergone surgery since iMRI became routine in TSS at the authors' institution. Residual tumor, complications, hormone dependency, biochemical remission rates, and improvement of vision were assessed at 6-month follow-up. A volumetric evaluation of residual tumor was performed in cases of parasellar tumor extension. Results The majority of patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6-month follow-up assessment, vision improved in 31% of patients who underwent iMRI-assisted surgery versus 23% in the conventional group. One instance of postoperative intrasellar bleeding was found in the conventional group. No major complications were found in the iMRI group. Minor complications were seen in 9% of patients in the iMRI group and in 5% of those in the conventional group. No differences between groups were found for hormone dependency and biochemical remission rates. Time of surgery was significantly lower in the conventional treatment group. Overall a residual tumor was found after surgery in 35% of the iMRI group, and 41% of the conventional surgery group harbored a residual tumor. Total resection was achieved as intended significantly more often in the iMRI group (91%) than in the conventional group (73%) (p < 0.034). Patients with a planned subtotal resection showed higher mean volumes of residual tumor in the conventional group. There was a significantly lower incidence of intrasellar tumor remnants in the iMRI group than in the conventional group. Progression-free survival after 30 months was higher according to Kaplan-Meier analysis with the use of iMRI, but a statistically significant difference could not be shown. Conclusions The use of high-field iMRI leads to a significantly higher rate of complete resection. In parasellar tumors a lower residual volume and a significantly lower rate of intrasellar tumor remnants were shown with the technique. So far, long-term follow-up is limited for iMRI. However, after 2 years Kaplan-Meier analyses show a distinctly higher progression-free survival in the iMRI group. No significant benefit of iMRI was found for biochemical remission rates and improvement of vision. Even though the surgical time was longer with the adjunct use of iMRI, it did not increase the complication rate significantly. The authors therefore recommend routine use of high-field iMRI for pituitary surgery, if this technique is available at the particular center.

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