scholarly journals Large Tumour Volume Reduction of Idh Mutated Anaplastic Glioma Involving the Insular Region Following Radiation Therapy: an Alternative to Maximal Surgical Resection

2021 ◽  
Author(s):  
Gabrielle Metz ◽  
Dasantha Jayamanne ◽  
Helen Wheeler ◽  
Matthew Wong ◽  
Raymond Cook ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Residual Disease ◽  
Insular Cortex ◽  
Tumour Volume ◽  
Anaplastic Glioma ◽  
Volume Reduction ◽  
Large Tumour ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Limited Surgery

Abstract Background: In IDH-mutated anaplastic glioma (IDHmutAG) of the insular cortex there remains uncertainty of benefit with near-total resection compared to limited surgery with radiation therapy (IMRT). This study aimed to assess tumour volume reduction in patients following IMRT and impact of residual post-surgical volume. Methods and Materials:Patients with IDHmutAG involving insular cortex managed with IMRT from 2008-2019 had baseline patient, tumour and treatment factors recorded. Volumetric assessment of residual disease on MRI was performed at baseline, month+3 and month+12 post-IMRT. Potential prognostic factors were analysed for tumour reduction and relapse-free survival, and assessed by log-rank and Cox regression analyses. Results: 32 patients with IDHmutAG of the insular cortex were managed with median follow-up post-IMRT of 67.2 months. Pathology was anaplastic astrocytoma (AAmut) in 20, and anaplastic oligodendroglioma (AOD) in 12 patients. Median pre-IMRT volume on T1 and T2Flair was 24.3cm3 and 52.2cm3. Twenty-seven patients were alive with 5-year relapse-free survival of 80%. There was a median 67% and 64% reduction from baseline occurring at 3 months post-IMRT for T1 and T2Flair respectively; and subsequent median 78% and 73% at 12 months. At 12 months AOD patients had median 83% T1 volume reduction compared to 63% in AAmut (p<0.01). There was no difference on T2Flair volume (p=0.64). No other pathological factors influenced volume reduction at 12 months. No factors were associated with relapse-free survival including baseline T1 (p=0.52) and T2Flair (p=0.93) volume.Conclusion:IMRT provides large tumour volume reduction in IDHmutAG of the insular cortex with no significant negative impact of residual disease volume on relapse-free survival.

THE ROLE OF SURGICAL STAGE IN COMBINATION THERAPY FOR PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 749-755
Author(s):  
D. Reyes Santyago ◽  
Anzhella Khadzhimba ◽  
M. Smirnova ◽  
Sergey Maksimov
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Combination Therapy ◽  
Lymph Nodes ◽  
Locally Advanced ◽  
Advanced Cervical Cancer ◽  
Relapse Free Survival ◽  
Regional Lymph Nodes ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer

Objective: to justify the expediency of the surgical stage as a part of the combination treatment for stage IIA-IIIB cervical cancer. Materials and methods. The study included 343 women with stage IIA-IIIB cervical cancer treated from 2013 to 2016 with mandatory follow-up for at least 2 years. Patients were divided into 2 groups. The first group included 214 patients who received a combination treatment. At the first stage, neoadjuvant chemoradiation therapy was performed (remote radiation therapy 5 days a week with radio modification with Cisplatin once a week at a dose of 40 mg/m2). After evaluating the effect, patients were subjected to surgical treatment or continued chemoradiotherapy. The second group (n = 129) received standard combined radiation therapy. Various schemes of combination and complex treatment and standard combined radiation therapy were evaluated using the indices of general and relapse-free survival. Results. The proposed scheme for the combination therapy for patients with locally advanced cervical cancer showed significantly higher survival rates at all the analyzed stages. For the combined treatment group with complete cytoreduction, the two-year overall and relapse-free survival with stage IIA is 94.1% vs. 82.4%, with IIB 90.8% vs. 80.3%, with IIB 87.5% vs. 75%, with IIB with metastatic lesion of regional lymph nodes 85% vs. 70%. For the second group, two-year overall and relapse-free survival with stage IIA 75% vs. 50%, with IIB 70.9% vs. 56.3%, with IIB 59.1% vs. 40.9%, with IIB with metastatic lesion of regional lymph nodes 62.2% and 40.5%. The advantages of this approach are most clearly seen within patients with metastatic lesions of regional lymph nodes (85% vs. 62% accordingly). Conclusion. Cytoreductive surgery in combination with the combination therapy allows to achieve a significant increase in overall and relapse-free survival for patients with locally advanced cervical cancer compared with standard treatment programs.

scholarly journals Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome–Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study

2017 ◽  
Vol 35 (16) ◽  
pp. 1795-1802 ◽  
Author(s):  
Giovanni Martinelli ◽  
Nicolas Boissel ◽  
Patrice Chevallier ◽  
Oliver Ottmann ◽  
Nicola Gökbuget ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Response ◽  
Minimal Residual

Purpose Few therapeutic options are available for patients with Philadelphia chromosome–positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) −based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph+ ALL. Patients and Methods This open-label phase II study enrolled adults with Ph+ ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naïve responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph+ ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous experience in Ph– ALL.

Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.

1998 ◽  
Vol 16 (11) ◽  
pp. 3518-3523 ◽  
Author(s):  
M P Mehta ◽  
S P Tannehill ◽  
S Adak ◽  
L Martin ◽  
D G Petereit ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Response Rate ◽  
Small Cell ◽  
Small Cell Lung ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Accelerated Radiation Therapy

PURPOSE To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.

Recurrence Patterns of Non-Mycosis Fungoides Cutaneous Lymphoma Following Various Treatment Modalities.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4676-4676
Author(s):  
Michael E. Confer ◽  
Jonathan D. Tward ◽  
Sherrie L. Perkins ◽  
Glen M. Bowen ◽  
Robert J. Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
B Cell ◽  
Initial Treatment ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract INTRODUCTION: Non-mycosis fungoides (MF) primary cutaneous lymphoma (PCL) is rare, and the more indolent forms seldom progress to fatal, systemic lymphoma. Nevertheless, frequent relapses are common. Although several therapies exist, no standard of care has been established for initial treatment. OBJECTIVES: To compare the role of radiotherapy to other initial treatment options and to evaluate clinicopathologic factors affecting overall, cause-specific, and relapse-free survival METHODS: Thirty-eight patients from 1985 to 2006 were retrospectively identified and reviewed with non-MF PCLs including: primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle-center lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, or primary cutaneous intravascular large B-cell lymphoma. Regression-free, cause-specific, and overall survival was estimated using the methods of Kaplan and Meier. Outcomes were compared with the log-rank test and Cox regression analysis. RESULTS: 38 patients were included in the analysis with a median follow-up time of 34.6 months (range 2 – 138 months). The distribution of initial treatment was: surgery - 29%, topical therapy - 16%, systemic therapy - 18%, and radiation - 63%. Three patients never received radiation. For the entire cohort, the 5-year overall (OS), cause-specific (CSS), and relapse free survival (RFS) was 86.2%, 88.9%, and 29.5% respectively. Subjects who received radiation therapy (n=24) as part of their initial treatment course had a significantly longer median time to first relapse of 57 months compared to 3.2 months for the 14 subjects who did not receive radiotherapy (log-rank p &lt; 0.0001). Overall survival was significantly improved for subjects whose International Prognostic Index (IPI) score was 0–1 (n=25) versus those whose score was 2 or greater (n=13, p=0.05). Multivariate analysis for RFS revealed that the absence of radiation as part of initial treatment (Hazard Ratio (HR) = 22.2, 95% CI 2.1 – 238.5, p=0.01) and aggregate size less than 10cm (HR 0.04, 95% CI 0.0 – 0.3, p&lt;0.01) significantly altered the risk of relapse. No relapses were observed within the radiation therapy treatment field in 31/35 (89%) subjects following their first course of radiation therapy. Of the 15/35 (43%) of patients that relapsed anywhere following radiation, only 2/15 (13%) relapsed in-field exclusively, 2/15 (13%) relapsed both in and out-of-field, and the remaining 11/15 (73%) relapsed exclusively outside the area treated. No patient relapsed within the treatment field of after 24 months. CONCLUSION: An initial course of radiation therapy significantly delays relapse compared to other therapies for non-MF PCL and provides excellent local control of plaques. Our findings also extend the IPI as prognostic for overall survival for this rare disease. Bulky lesions greater than 10cm in any one dimension are more strongly correlated with relapse.

Fluctuating Values of Molecular Residual Disease (MRD) without Molecular Progression After Imatinib Discontinuation in Patients (pts) with Chronic Myeloid Leukemia (CML) Who Have Maintained Complete Molecular Response: Implications for Re-Treatment Criteria and Role of Prior Interferon Therapy. A Pilot Study of the French CML Group (FILMC),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3781-3781 ◽  
Author(s):  
Philippe Rousselot ◽  
Pascale Cony Makhoul ◽  
Delphine Rea ◽  
Philippe Agape ◽  
Franck E Nicolini ◽  
...  
Keyword(s):  
Interferon Therapy ◽  
Residual Disease ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Relapse Free Survival ◽  
First Line ◽  
Free Survival ◽  
Low Levels ◽  
Sokal Score

Abstract Abstract 3781 Background. We have reported the results of imatinib discontinuation in CML pts in complete molecular response (CMR) for more than 2 years under imatinib therapy (STIM study, Mahon et al. Lancet Oncol. 2010). Among the group of pts without confirmed molecular relapse, a small proportion exhibited low levels of detectable residual disease during a prolonged period of time. Aims. In order to better characterize this phenomenon, we decided to analyse pts who stopped IM following a maintained CMR or an undetectable molecular residual disease (UMRD) and resumed therapy upon loss of major molecular response (MMR). We also aimed to validate the loss of MMR as a robust criterion for the re-introduction of tyrosine kinase inhibitors (TKIs). Patients and methods. CP-CML pts were eligible if they were in CMR (CMR4.5: BCR-ABL/ABL IS ratio <0.0032%) or UMRD (undetectable Bcr-Abl using standardized RTQ-PCR) under imatinib therapy for more than 2 years. Those pts were not enrolled in the STIM study because the study was closed or because they experienced at least one positive value of the BCR-ABL/ABL ratio during the 2 years follow-up. The proposed criterion for resuming imatinib was the loss of MMR (BCR-ABL/ABL IS ratio >0.1%). We calculated relapse free survival (RFS) using three different end-points: First loss CMR/UMRD defined by one occurrence MRD positivity; second loss of CMR/UMRD using the STIM definition (two consecutive increasing values of MRD); third loss of MMR. We also described pts with long lasting fluctuating PCR values. Results. 34 CP-CML pts were included in the analysis. Median follow-up after imatinib discontinuation was 21.3 months (2.2–83.1). Sex ratio (M/F) was 50% with a median age of 54.1 years (27.4–78.2). Sokal score distribution was 34.5%, 37.9% and 27.6% for low, intermediate and high values respectively. 19 out of 34 (55.9%) of the pts received interferon therapy prior to imatinib. Median duration of imatinib therapy and median duration of CMR/UMRD prior to discontinuation was 63.8 months (30.1–120.8) and 33.7 months (7.3–72.8) respectively (only two pts had CMR/UMRD duration less than 2 years). Of note 18 out of 34 pts (52.9%) had a least one MRD positive value after the achievement of CMR/UMRD. After imatinib discontinuation, we identified 11 pts (32.4%) who experienced repeated low levels of detectable MRD without losing their MMR. Median follow-up for these pts with fluctuating values of MRD was 15.4 months (3.5–59.5) and none of them restarted imatinib. We next analysed relapse free survival (RFS) using the loss of MMR criteria (RFS-MMR). Median RFS-MMR was not reached, compared to median RFS using the loss of CMR/UMRD criteria (4.8 months) and median RFS using the STIM criteria (13.8 months) (p=0.003). As a consequence, 62.8% of the pts remain treatment free at 2 years using the loss of MMR criteria for resuming imatinib. Fluctuating values of MRD has already been described after interferon cessation in CML interferon treated pts. We thus asked if prior therapy with interferon before imatinib may influence treatment free survival. Duration of imatinib therapy and Sokal score risk distribution were comparable between pre-treated and non pre-treated pts (p=0.7). However, the median RFS was longer in interferon pre-treated pts as compared to pts who received imatinib first line (not reached versus 7 months, p=0.047). Furthermore, this difference was not significant using the loss of CMR/URMD (p=0.27) to define molecular relapse. Conclusions. We were able to identify a significant number of pts with fluctuating values of MRD after imatinib discontinuation, a proportion underestimated in previous studies. We also validated the loss of MMR as the most accurate and robust criteria for restarting imatinib after imatinib discontinuation. Applying this criterion, we demonstrated that treatment free survival is significantly better in pts previously treated with interferon before imatinib compared to pts who received imatinib as first line therapy. An update of this pilot study on a larger number of patients will be presented. Disclosures: Rousselot: BMS, Novartis: Research Funding. Tulliez:Novartis:. Mahon:Novartis Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria; Pfizzer: Honoraria.

Decision-Making At The End Of Consolidation Of Acute Myeloid Leukemia: Negative Effect Of Minimal Residual Disease Detectable With Multiparametric Flowcytometry Combined With Gene Mutations Of FLT3 On Early Relapse

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3921-3921
Author(s):  
Yuichiro Ono ◽  
June Takeda ◽  
Hayato Maruoka ◽  
Yasuhiro Kazuma ◽  
Nobuhiro Hiramoto ◽  
...  
Keyword(s):  
Decision Making ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Gene Mutations ◽  
Decision Making Process ◽  
Consolidation Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Background About 70-80% of adult patients (pts) with acute myeloid leukemia (AML) achieve complete remission (CR); however, around a half of them experience a relapse. For the purpose of creating accurate decision-making process of post-consolidation strategy, stratification system using karyotype and recurrent gene mutations have been widely utilized. As is confirmed in childhood acute lymphocytic leukemia, however, the information of minimal residual disease (MRD) status would substantially improve the reliance of decision-making process of adult AML pts. Unfortunately, approximately a half of AML patients lack molecular targets suitable for MRD monitoring. The aims of this study are to evaluate the applicability of MRD detection using multiparametric flow cytometry (MPFC) and to estimate the impact of MRD measured with MPFC at the end of consolidation therapy in improving decision-making process. Patients and Methods We retrospectively studied 81 consecutive pts with newly diagnosed AML who received induction therapies and achieved CR in our institute between January 2007 and March 2013. Pts with acute promyelocytic leukemia were excluded. We routinely analyzed the bone marrow specimens with MPFC for the detection of leukemia-associated immunophenotypes (LAIPs) at diagnosis. Since April 2010, RT-PCR assay examined FLT3-ITD mutation in the same specimens. In pts who had traceable LAIPs, the relationships of the levels of MRD at the end of consolidation therapy with relapse free survival were analyzed. Positive MRD was defined as the detection of 0.2% and more LAIPs-positive cells with MPFC. We compared two patient groups: those with MRD at the end of consolidation (MRDp group) and those without (MRDn group). Relapse-free survival (RFS) was analyzed using the Kaplan-Meier method and the log-rank test was used for comparison between each group. A multivariate Cox regression analysis for RFS was fit to assess the effect of the followings: age at diagnosis (≥ vs. < 65 years old), the number of induction regimens required for achieving CR (≥ vs. < 2 times), cytogenetic risk groups of SWOG (unfavorable vs. favorable/intermediate). Results In 57 / 81 pts, MPFC could detect LAIPs in the bone marrow specimens at diagnosis (70.4% of all subjects; 15-82 years-old; follow-up time [median] 98-2211[517] days). FLT-ITD mutations were found in 13 pts, but not in 39 pts (the remaining 5 pts were not examined). The rate of detection of LAIPs with 6-color MPFC was significantly superior to 3-color MPFC (82.1% vs. 61.0%, p<0.05). Induction chemotherapies the pts received were anthracyclin-containing regimens, such as idarubicin and cytarabin (3+7), in 52 pts (91.2%), low-dose cytarabin-based regimen in 4 pts (7.0%) and azacitidine in 1 pt. (1.8%). The MRDp and the MRDn groups were comprised of 20 and 37 pts (35.1% and 64.9%) , respectively. One-year RFS of the MRDp group was significantly inferior to the MRDn group (28.3% vs. 75.2%; log-rank p<0.0005). In the multivariable analysis using the model above, MRD positivity at the end of consolidation remains a significant predictor (HR, 2.93, 95% CI 1.16-7.45, p<0.05). In addition, the 1-year RFS in the MRDp group with FLT-ITD was significantly shorter than that in the MRDp group without FLT3-ITD (0% vs. 47.6% with positive and negative FLT3-ITD, log-rank p<0.05). In the MRDn group, however, the negative impact of FLT3-ITD was not documented (85.7% vs. 69.3% with positive and negative FLT3-ITD, log-rank p=0.954). Conclusion Our retrospective study confirmed that LAIPs as MRD targets were applicable to the majority of pts with AML; MRD positivity measured with LAIPs was a promising predictor for early relapses at the end of consolidation, as was previously reported. When combined with FLT-ITD status, it might become a more sensitive prognostic factor. Disclosures: Takahashi: celgene: Research Funding.

Phase II study of consolidative intensity-modulated radiation therapy following first-line palliative systemic chemotherapy for de novo previously untreated metastatic (M1) nasopharyngeal carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6524-6524
Author(s):  
Victor Ho-Fun Lee ◽  
Ann SY Chan ◽  
Dora LW Kwong ◽  
To-Wai Leung ◽  
Sherry CY Ng ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Progressive Disease ◽  
De Novo ◽  
Phase Ii Study ◽  
Intensity Modulated Radiation Therapy ◽  
Relapse Free Survival ◽  
First Line ◽  
Free Survival ◽  
Intensity Modulated ◽  
Line Chemotherapy

6524 Background: The prognosis of de novo previously untreated metastatic (M1) nasopharyngeal carcinoma (NPC) at diagnosis is poor, and the role of consolidative intensity-modulated radiation therapy (IMRT) to the primary tumor and the neck following first-line palliative chemotherapy remains unknown. We report a phase II study of consolidative IMRT after first-line chemotherapy in previously untreated M1 NPC. Methods: Consolidative IMRT was given in prospectively recruited patients whose previously untreated M1 NPC did not progress after 6 cycles of first-line chemotherapy with gemcitabine and cisplatin. The primary study objective was overall survival (OS). Secondary objectives included progression-free survival (PFS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS), response and toxicity. Results: Sixty-nine consecutive patients were enrolled. Sixty-four (92.8%) patients received first-line chemotherapy, of which 8 (12.5%) developed progressive disease and another 8 (12.5%) did not receive IMRT despite non-progression to first-line chemotherapy. The remaining 48 patients whose disease controlled after chemotherapy received IMRT, including 18 (37.5%) who received concurrent chemoradiation. OS was significantly better in those who received IMRT (35.1 versus 14.2 months; P < 0.001), after a median follow-up duration of 3.40 years (range 0.43 years to 12.14 years). PFS, LRFS, and RRFS were also significantly longer in those who received IMRT. Multivariable analyses revealed that IMRT was the only prognostic factor of all survival endpoints. Grade 3 adverse events were observed in 10 (20.8%) patients, mainly mucositis, dysphagia and desquamation. Conclusions: Consolidative IMRT was associated with an OS benefit and favorable tolerability among previously untreated M1 NPC patients who had non-progressive disease following first-line chemotherapy. These results support the rationale to further investigate IMRT as part of the initial treatment in this setting. Clinical trial information: NCT02476669 .

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